Conditions

Front 1

obesity, excessive and indiscriminate eating habits, small hands and feet, short stature, hypogonadism and MR, sterility, scoliosis, osteoporosis, triangular mouth, almond-shaped eyes, small hands and feet, narrow bifrontal diameter, hypopigmentation of hair/skin/eyes

Back 1

PWS

Front 2

___% of PWS due to cytogenetic deletion involving ___ (area of chromosome), __% due to maternal UPD, ___ due to imprinting issue.

Back 2

70%, 30%, rarely

Front 3

In PWS and Angelman Syndrome, the imprinting issue is not switching from __ to ___ imprinting during spermatogenesis or from ___ to ___ imprinting during oogenesis

Back 3

female to male, male to female

Front 4

unusual facial appearance, short stature, severe MR, spasticity, seizures, hand flapping, loving water

Back 4

Angelman Syndrome

Front 5

__% of Angelman Syndrome due to cytogenetic deletion involving __ (area of chromosome), __% due to paternal UPD, __% due to imprinting issue, and __% due to mutations in maternal E6-AP ubiquitin protein ligase gene.

Back 5

70%, 3-5%, rarely, rarely

Front 6

very large at birth, enlarged tongue, frequent protrusion of umbilicus, severe hypoglycemia, malignant neoplasms of kidney, adrenal, and liver, earlobe creases, postauricular pits, facial nevus flammeus, visceromegaly, omphalocele, Wilms tumors

Back 6

BWS

Front 7

BWS results from excess of ___ genes or loss of ___ genes contribution to chromosome ___

Back 7

paternal, maternal, 11p15

Front 8

BWS gene defect includes a gene called ___

Back 8

insulin-like growth factor 2

Front 9

defect in DNA helicase leading to striking increase in somatic recombination and sister chromatid exchange, IUGR, hyper/hypopigmentation, butterfly telangectasia, microcephaly, high pitch voice, normal IQ, immunodeficiency, azoospermia, POF, increased risk for cancer

Back 9

Bloom Syndrome

Front 10

deficiency in one of the DNA methyltransferases required for establishing and maintaining normal patterns of DNA methylation in genome, abnormal association of pericentromeric heterochromatin involving chromosomes 1,9,16

Back 10

ICF syndrome

Front 11

immunodeficiency, centromeric instability, facial anomalies

Back 11

ICF syndrome

Front 12

most common genetic cause of moderate MR

Back 12

TS 21

Front 13

1 child in ___ is born with TS 21 and among children or fetuses of mothers 35yo +, incidence rate is ___.

Back 13

800, higher

Front 14

TS 21 has ___ concordance in MZ twins and ___ in DZ twins

Back 14

high, complete

Front 15

hypotonia, short stature, brachycephaly, flat occiput, neck short, loose skin on nape, nasal bridge flat, ears low-set and folded, eyes have Brushfield spots around margin of iris, mouth is open with furrowed protruding tongue, epicanthal folds, upslanting palpebral fissues, hands short and broad with single transverse palmar crease, incurved fifth digits (clinodactyly), dermatoglyphs characteristic, sandal gap between first and second toes, MR 30-60 IQ, congenital heart disease, duodenal atresia, tracheoesophageal fistula

Back 15

TS 21

Front 16

congenital heart disease seen in at least ___ of all liveborn infants with DS and ___ in abortuses

Back 16

1/3, higher

Front 17

___% of TS 21 conceptuses survive to birth and least likely to survive if have ____.

Back 17

20-25%, congenital heart disease

Front 18

What type of cancer are people with DS at increased risk of? How much more?

Back 18

15x, leukemia

Front 19

People with TS 21 are at higher risk of what neurological condition?

Back 19

premature dementia/Alzheimer disease

Front 20

___% of trisomy 21 due to meiotic error during maternal meiosis (esp. meiosis ___) and ___% during paternal meiosis (esp. meiosis ___).

Back 20

90%, I, 10%, II

Front 21

___% of people with DS have a Robertsonian translocation?

Back 21

4%

Front 22

How many possible types of gametes can someone who is a carrier of a Robertsonian translocation with 21q have? How many viable?

Back 22

6 total, 3 viable (normal, balanced, unbalanced with one normal and one translocated)

Front 23

Risk of DS by logic should be 1 in ___ for a balanced robertsonian translocation, but unbalanced complements actually show up ___% of the time when mom is a carrier and ___% when dad is carrier

Back 23

3, 10-15%, 3%

Front 24

21q21q translocation is seen in ___% of DS patients. RR is ___ because ___.

Back 24

3%, low because all gametes of carrier must contain 21q21q with either double 21q OR lacking chromosome 21 (rarely viable)

Front 25

21q21q originates how?

Back 25

isochromosome, postzygotically

Front 26

__% of DS patients are mosaic?

Back 26

2%

Front 27

One area of chromosome 21 is responsible for ___% of heart defects in DS

Back 27

40%

Front 28

the idea that older oocytes have greater chance of not disjoining, may be less able to overcome susceptibility to nondisjunction established by recombination machinery

Back 28

older egg model

Front 29

80% of prenatal diagnosis for DS d/t ___ or ___

Back 29

AMA or prenatal biochemical screening

Front 30

>50% of mothers of DS are how old?

Back 30

younger than 35

Front 31

50% or more pregnant women >35yo get prenatal Dx and only ___% of fetuses tested have TS 21

Back 31

1%

Front 32

recurrence risk for DS in families with one affected child? in mothers with one affected child and <30yo? in families with DS in family but not in child?

Back 32

1 child: 1%, <30yo: 1.4%, no elevated risk where not in child

Front 33

MR, FTT, severe malformation of heart, hypertonia, prominent occiput, jaw recedes, low-set and malformed ears, short sternum, fists clench with 2nd/5th digits overlapping 3/4, rocker-bottom fet, single creases on palm and arch patterns on most or all digits, hypoplastic nails, delayed growth, omphalocele

Back 33

TS 18

Front 34

___% of TS 18 conceptuses aborted spontaneously

Back 34

95%

Front 35

>60% of TS 18 conceptuses are ___?

Back 35

female

Front 36

growth retardation, severe MR, severe CNS malformations (holoprosencephaly, arhinencephaly), forehead sloping, microcephaly, wide open suture, micropthalmia, iris coloboma, absence of eyes, malformed ears, CL/CP, post-axial polydactyly, hands clenched with 2/5 overlapping 3/4, rocker-bottom feet, single palmar crease, congenital heart defects (VSD's, patent ductus arteriosus), urogenital defects (cryptorchidism in males, bicornuate uterus, hypoplastic ovaries, polycystic kidneys)

Back 36

TS 13

Front 37

___% of patients with TS 13 will die within first month

Back 37

50%

Front 38

TS 13 usually arises in meiosis ___ due to ___

Back 38

I, nondisjunction

Front 39

___% of cases of TS 13 are caused by unbalanced translocation

Back 39

20%

Front 40

recurrence risk of having a liveborn child with TS 13 d/t a balanced translocation is ___%

Back 40

<2%

Front 41

crying sounds like mewing cat, microcephaly, hypertelorism, epicanthal folds, low-set ears with pre-auricular tags, micrognathia, mod to severe MR and heart defects

Back 41

Cri du chat

Front 42

terminal or interstitial del on 5p

Back 42

Cri du Chat

Front 43

condition accounting for 1% of all institutionalized MR patients

Back 43

Cri-du-Chat

Front 44

most cases of Cri-du Chat are ____, but ___% are due to translocation of 5p15

Back 44

sporadic, 10-15%

Front 45

to diagnose Cri du Chat, you can use __ and ___

Back 45

FISH, aCGH

Front 46

tall male, eunuchoid build, infertile, hypogonadism, learning difficulties, poor psychosocial adjustment sometimes, gynecomastia, increased risk of breast cancer, androgen deficiency, increased cholesterol, inc risk of autoimmune disorders and mediastinal germ cell tumors

Back 46

47,XXY (Klinefelter)

Front 47

tall male, frequently psychosocial issues, normal gonad-wise and MR wise, fertility normal, seen more in prisons, hypotonia, motor tics

Back 47

XYY syndrome

Front 48

female, usually tall, usually normal fertility, some patient have learning difficulties, occasionally severe psychopathological and antisocial beahvior, IQ lower, hypotonia

Back 48

trisomy X (47, XXX)

Front 49

short female, distinctive features, infertile, streak gonads, slightly reduced learning ability

Back 49

turner syndrome (45,X)

Front 50

what is the error that produces 47,XYY males?

Back 50

paternal nondisjunction at meiosis II

Front 51

what errors have occured in XXYY and XXXYY variants of klinefelters?

Back 51

sequential nondisjunction in meiosis I and meiosis II in dad

Front 52

error causing trisomy X?

Back 52

maternal meiosis, mostly meiosis I and is AMA associated

Front 53

what kind of phenotype does 49,XXXXX have?

Back 53

severe developmental retardation with multiple physical defects

Front 54

most frequent karyotype for Turner Syndrome? %?

Back 54

45,X, 50%

Front 55

other possible karyotypes for Turner Syndrome

Back 55

46,X,i(Xq)- 15%, 45,X/46,XX mosaic- 15%, 45,x/46,X,i(Xq) mosaic- 5%, 45,X, other X abnormality- 5%, other 45,X/? mosaics- 5%

Front 56

phenotype of i(Xq) with deletions of Xp v. Xq?

Back 56

Xp: short stature and congenital malformations, Xq: gonadal dysfunction

Front 57

short stature, gonadal dysgenes, characteristic facies, short metacarpals, webbed neck, low posterior hairline, broad chest with widely spaced nipples, elevated frequency of renal/cardiovascular anomalies, edema of dorsum of foot in infancy, coarctation of aorta (50%), hypoplastic L heart, cystic hygroma prenatally, lymphedema, primary/secondary amenorrhea, DD, deficiency in spatial perception/fine motor/perceptual motor organization, nonverbal IQ <verbal IQ, educational intervention, social adjustment issues, scoliosis, micrognathia, delayed epiphyseal fusion, infertility

Back 57

Turner Syndrome

Front 58

___% of all conceptuses have Turner Syndrome, ___% abort spontaneously

Back 58

1-2%, 99%

Front 59

single X in Turner Syndrome maternal in origin ___% of time so loss is usually ___ chromosome

Back 59

70%, paternal

Front 60

phenotype for small ring X chromosomes? reason?

Back 60

short stature, gonadal dysgenesis, MR, syndactyly- more severe than turner Syndrome maybe because lacking X inactivation center leading to over-expression

Front 61

conditions caused by SOX9 mutations

Back 61

XY female with camptomelic dysplasia or XX male

Front 62

condition caused by SF1 mutation

Back 62

XY sex reversal and adrenal insufficiency

Front 63

conditions caused by WT1 mutations

Back 63

XY female with Frasier Syndrome or male pseudohermaphrodite with Denys-Drash syndrome

Front 64

condition caused by DAX1 mutation

Back 64

XY female with gene duplication

Front 65

condition caused by ATRX mutation

Back 65

XY sex reversal

Front 66

condition caused by WNT4 mutation

Back 66

XY female with cryptorchidism (gene dup)

Front 67

condition caused by FOXL2 mutation

Back 67

premature ovarian failure

Front 68

inheritance of camptomelic dysplasia

Back 68

ad

Front 69

___% of 46,XY patients with camptomelic dysplasia are sex reversed and female phenotypically

Back 69

75%

Front 70

Testes fail to form in absence of one copy of ___ gene and ovarian pathway followed

Back 70

SOX9

Front 71

Duplication of SOX9 leads to ____, suggesting overproduction of SOX9 even without SRY can initiate testis formation

Back 71

XX sex reversal

Front 72

Males with Denys-Drasher have what kind of genitalia?

Back 72

ambiguous

Front 73

function of WT1 gene

Back 73

encodes TF involved in interactions between sertoli and leydig cells in developing gonads

Front 74

X-linked MR and alpha thalassemia, undescended testes to micropenis, XY sex reversal

Back 74

X-linked ATRX gene

Front 75

Loss of Xq frequently leads to ___ in females

Back 75

premature ovarian failure

Front 76

Mutations in FOXL2 are seen in patients with ____ syndrome, leading to ovarian dysgenesis to premature ovarian failure in females

Back 76

blepharophimosis/ptosis/epicanthus inversus (BPES) syndrome

Front 77

46,XX karyotype with normal ovarian tissue but ambiguous or male external genitalia

Back 77

female pseudohermaphroditism

Front 78

CAH accounts for ___% of all cases presenting with ambiguous genitalia

Back 78

50%

Front 79

CAH leads to normal ovarian development, but excessive production of ____ leading to masculinization of external genitalia with ___ and ___

Back 79

androgens, clitoral enlargement, labial fusion

Front 80

most common CAH deficiency is of ___

Back 80

21-hydroxylase

Front 81

affected males with 21-hydroxylase deficiency have ___ genitalia

Back 81

normal

Front 82

___% of patients with 21-hydroxylase deficiency have simple virilizing type and __% have salt-losing type due to mineralocorticoid deficiency

Back 82

25%, 75%

Front 83

which is more severe and leads to neonatal death: virilizing type 21-hydroxylase or salt-losing type

Back 83

salt-losing type

Front 84

pathway misfunctioning in 21-hydroxylase deficiency

Back 84

blocks normal biosynthetic pathway of glucocorticoids and minerlocorticoids leading to overproduction or precursors, shunted into pathway of androgen biosynthesis causing high androgen levels in XX and XY embryos

Front 85

treatment for 21-hydroxylase deficiency

Back 85

hormone replacement

Front 86

46,XY with incompletely masculinized internal and external genitals or female external genitalia

Back 86

male pseudohermaphroditism

Front 87

male pseudohermaphroditism is due to abnormalities of ____ and thus __testosterone biosynthesis and metabolism and abnormalities of androgen target cells

Back 87

gonadotropins, testosterone

Front 88

what enzyme is responsible for converting male hormone testosterone to active form dihydrotestosterone

Back 88

5alpha-reductase

Front 89

symptoms of 5alpha-reductase deficiency?

Back 89

feminization of external genitalia in affected males, testes normal, penis small, blind vaginal pouch

Front 90

46,XY with normal female external genitalia, blind vagina, no uterus or uterine tubes, sparse or absent axillary/pubic hair, testes present within abdomen or inguinal canal, psychosocial development, and sexual function that of normal female except infertile

Back 90

androgen insensitivity syndrome/testicular feminization

Front 91

in androgen insensitivity syndrome, testes secrete androgen, but organs ___ due to absence of ___

Back 91

unresponsive to androgen, androgen receptors in target cells

Front 92

neurofibromas, CAL spots, hamartomas/Lisch nodules on iris, MR, CNS tumors, diffuse plexiform neurofibromas, cancer of muscle or CNS, variable expressivity, AD inheritance

Back 92

NF1

Front 93

__% of NF1 mutations are de novo

Back 93

50%

Front 94

NF1 has ___ expressivity, but is ___% penetrant

Back 94

variable, 100%

Front 95

Malformation in split-hand deformity/ectrodactyly originates in ___ weeks of development

Back 95

6-7th

Front 96

___% penetrance in split hand deformity/ectrodactyly

Back 96

70%

Front 97

split-hand deformity/ectrodactyly shows what principle well since many loci recognized to cause same phenotype?

Back 97

locus heterogeneity

Front 98

dominantly inherited failure of development of colonic ganglia leading to defective colonic motility and severe chronic constipation, also leads to megacolon proximal to aganglionic segment

Back 98

Hirschsprung disease

Front 99

conditions with RET mutations

Back 99

Hirschsprung, MEN 2A and MEN 2B

Front 100

conditions caused by LMNA mutations

Back 100

Emery-Dreifuss MD, hereditary dilated CM, one form of CMT, lipodystrophy form, Hutchinson-Gifford progeria

Front 101

females affected with hemochromatosis are affected with this condition 1/5 to 1/10 times that of males d/t___, ___, and ___

Back 101

lower dietary intake of iron, lower alcohol usage, and increased iron loss through menstruation

Front 102

__% of N. european individuals are homozygous for HFE mutations

Back 102

0.5%

Front 103

normal development until 6mo then blindness, regression mentally and physically beginning at 6mo, cherry red spot, fatal in early childhood around 2-3yo

Back 103

Tay Sachs

Front 104

short-limbed rhizomelic disproportionate dwarfism, large head, normal IQ, flat midface, bowed limbs, brachydactyly, lordosis, long and narrow trunk, trident hands, prominent forehead, hypotonia, hyperextensible joints, forament magnum stenosis with brainstem compression, obstructive apnea, otitis media, FTT, sudden death rarely

Back 104

achondroplasia

Front 105

homozygotes with achondroplasia phenotype

Back 105

more severely affected and usually don't survive postnatal period

Front 106

AD disorder leading to premature coronary heart dz due to atheromas (deposits of LDL cholesterol in coronary arteries), xanthomas (cholesterol deposits in skin and tendons), arcus corneae (deposits of cholesterol around periphery of cornea)

Back 106

familial hypercholesterolemia

Front 107

homozygotes with familial hypercholesterolemia phenotype

Back 107

earlier age of onset and shorter life expectancy

Front 108

boys develop secondary sex characteristics and undergo adolescent growth spurt at 4yo, normal fertility, epiphyseal fusion at early age so short as adults, females don't exhibit symptoms, AD

Back 108

male-limited precocious puberty/ familial testotoxicosis

Front 109

blood fails to clot normally due to deficiency of factor VIII, X-linked recessive inheritance

Back 109

hemophilia A

Front 110

how would you see X-linked color blindness in a female?

Back 110

mutated X present in both father and carrier mother

Front 111

examples of diseases where you might see manifesting heterozygotes

Back 111

color blindness, hemophilia A, hemophilia B, DMD, Wiskott-Aldrich syndrome, X-linked eye disorders

Front 112

Penetrance for Hunter Syndrome is very ___ because of ___

Back 112

low, X carrying normal gene is active and can export enzyme to be used in the cells with the mutant X which corrects the defect

Front 113

Cell survival and proliferative abilities is ___ in cells with mutant allele on active X chromosome in conditions like IP or dyskeratosis congenita

Back 113

low

Front 114

kidney tubules can't absorb filtered phosphate, serum level of phosphate depressed and rickets less severe in females than males

Back 114

X-linked hypophosphatemic rickets

Front 115

females affected, lethal in hemizygous males, normal growth and development then loss of milestones 6-18mo, spastic, ataxic, autistic, irritable behaviors, wringing of hands/arms, microcephaly, seizures, survival many decades after regression, reduced growth, poor/no speech, MR, metacarpal/tarsal hypoplasia

Back 115

Rett syndrome

Front 116

gene affected in Rett

Back 116

MECP2

Front 117

males who survive with Rett syndrome usually have what karyotype/gene changes?

Back 117

Klinefelters or 46,X,der(X) with SRY translocated from Y to X or mosaic for mutation absent in most of their cells

Front 118

Patients with hemophilia have only ___% as many offspring as unaffected males do, so fitness of affected male is ___

Back 118

70%, 0.7

Front 119

proximal muscle weakness, progressive muscle weakness from 3-5yo onand usually in wheelchair by 12yo, typically don't survive teens, seen mainly in boys but girls can be mildly affected, usually die of heart failure, elevated CK levels, modest decrease in IQ of 20 points

Back 119

DMD

Front 120

DMD has a ___ rate of new mutations because ___ is low

Back 120

high, fitness

Front 121

dominantly inherited skeletal dysplasia with disproportionate short stature and deformity of forearm, greater prevalence in females than males but have male-to-male transmission, mutation in SHOX gene in pseudoautosomal region and escapes X-inactivation

Back 121

dyschondrosteosis

Front 122

mutation in type I collagen leading to half the collagen, brittle bones but no deformity, frequent fractures, blue sclerae, AD inheritance

Back 122

OI type I

Front 123

___% of severe, lethal forms of OI have germline mosiaicsm

Back 123

6%

Front 124

___% of mom carry DMD germline mosaically, the highest incidence of all conditions

Back 124

15%

Front 125

obesity, short stature, subcutaneous calcifications, brachydactyly (esp 4th/5th metacarpals), haploinsufficiency for GNAS, round face, narrow lumbar canal, SC ossifications, DD (common and mild), pseudoparathyroidism may or may not be present depending on imprinting

Back 125

Albright hereditary osteodystrophy

Front 126

AHO with pseudohypoparathyroidism, hypothyroidism, growth hormone deficiency, haploinsufficiency for GNAS inherited from a female parents which also causes complete loss of expression in critical renal and endocrine tissues

Back 126

PHP1a

Front 127

AHO alone in a member of a family in which PHP1a is also occurring, constitutional haploinsufficiency for GNAS inherited from a male parent which leaves intact expression of maternal copy in critical renal and endocrine tissues

Back 127

PPHP

Front 128

only endocrine defects of PHP1a without features of AHO, mutation in imprinting center who normal function is required for expression of maternal copy of GNAS in critical renal and endocrine tissues, no loss of constitutional GNAS expression

Back 128

PHP1b

Front 129

AHO is a ___ penetrant AD trait, but some of affected patients have additional disorder called ____

Back 129

fully, pseudohypoparathyroidism

Front 130

PHP with AHO phenotype known as ___

Back 130

PHP1a

Front 131

when AHO is present without renal tubular dysfunction, called ___

Back 131

PPHP

Front 132

abnormality of calcium metabolism seen with deficiency of parathyroid hormone, elevated levels of parathyroid hormone secondary to renal tubular resistance to effects of parathyroid hormone

Back 132

pseudohypoparathyroidism

Front 133

when PPHP or PHP1a occur within same family, affected brothers and sisters either ALL have ____ or ALL have ____

Back 133

PPHP, PHP1a

Front 134

GNAS is imprinted only in certain tissues, so only GNAS inherited from ___ expressed while __ is silent

Back 134

mom, dad

Front 135

PHP1a occurs only when an individual inherits an ___ mutation in GNAS from their ___ since the other copy is not expressed

Back 135

inactivating, mother

Front 136

in tissues without GNAS imprinting, hets of mutation all develop ____, which is passed on with ____ inheritance

Back 136

AHO, AD

Front 137

calcium abnormalities seen in PHP1a but without physical signs of AHO is what condition?

Back 137

PHP1b

Front 138

When mutation of imprinting control region is inherited from ___ in PHP1b, both paternal and maternal allele fail to be expressed

Back 138

mom

Front 139

people who inherit GNAS mutation from ___ are asymptomatic heterozygotes because the other copy is intact and expressed normally

Back 139

dad

Front 140

repeat expanded in HD

Back 140

CAG

Front 141

normal, intermediate, and affected repeat range for HD

Back 141

<36 normal, 36-39 usually affected, >40 affected

Front 142

repeat expanded in FX

Back 142

CGG

Front 143

normal, intermediate, and affected repeat range in FX

Back 143

<45 normal, 46-54 grey zone, 60-200 usually unaffected, >200 affected

Front 144

FX gene mutation

Back 144

FMR1

Front 145

repeat expanded in myotonic dystrophy

Back 145

CTG

Front 146

normal, intermediate, and affected repeat range in myotonic dystrophy

Back 146

<30 normal, 50-80 mildly affected, 80-2000 affected

Front 147

myotonic dystrophy gene mutated

Back 147

DPMK

Front 148

Friedreich ataxia repeat expanded

Back 148

GAA

Front 149

normal, intermediate, and affected repeat range in Friedreich ataxia

Back 149

<34 normal, 36-100 intermediate, >100 affected

Front 150

gene mutated in Friedreich ataxia

Back 150

FRDA

Front 151

degeneration of striatum and cortex, presents clinically in midlife and manifest characteristic phenotype of motor abnormalities, personality changes, gradual loss of cognition, and death, results in long polyglutamine tracts in mutant protein

Back 151

HD

Front 152

anticipation for HD when transmitted through which parent?

Back 152

dad

Front 153

most common heritable form of moderate MR, second only to Down Syndrome among all causes of MR in males

Back 153

FX

Front 154

FX penetrance in females

Back 154

50-60%

Front 155

expansion of FX only happens when transmitted from which parent?

Back 155

mom

Front 156

__ of females with a premutation experience premature ovarian failure by 40yo

Back 156

1/4

Front 157

>200 repeats for FX leads to excessive methylation of ___ in promoter of FMR1 which interferes with ____; prevents normal promoter function or blocks ____

Back 157

cytosines, replication or chromatin condensation or both, translation

Front 158

muscular dystrophy, myotonia, cardiac conduction defects, cataracts, hypogonadism, diabetes, frontal balding, changes in EEG, congenital or adult form, transmitted through mom, AD inheritance; can be congenital form as well

Back 158

myotonic dystrophy

Front 159

in myotonic dystrophy, who can transmit amplified repeats?

Back 159

either, but males can pass on up to 1000 copies of repeat and more massive repeats can only be passed on from mom

Front 160

spinocerebellar ataxia, AR inheritence, manifested before adolescence, incoordination of limb movements, difficulty with speech, diminished or absent tendon reflexes, impairment of position and vibratory senses, CM, scoliosis, foot deformities

Back 160

Friedrich ataxia

Front 161

AAG repeat expansion in Friedrich ataxia is in what part of the gene?

Back 161

intron

Front 162

gene encoded by AAG repeat expansion in Friedrich ataxia is called ___ and functions in ___.

Back 162

frataxin, iron metabolism

Front 163

more expansion through __ in FRDA, DM, and FX, but in HD, largest expansion through ___.

Back 163

mom, dad

Front 164

AD Parkinson disease is due to a ___ of a 2-Mb region of chromosome 4q

Back 164

triplication

Front 165

X-linked choroideremia (retinal degeneration), deafness, and MR caused by a ___ of at least 3 loci in band Xq21

Back 165

deletion

Front 166

heterozygote for a missense mutation in one gene encoding photoreceptor membrane protein peripherin or for null allele encodin photoreceptor membrane protein Rom1 do not develop disease but those with bone mutations do develop this disease

Back 166

digenic RP

Front 167

clots form in venous system of brain causing occlusion of cerebral veins in absence of inciting event like tumor or infection

Back 167

idiopathic cerebral vein thrombosis

Front 168

___% of Caucasian population has an FVL mutation

Back 168

2.5%

Front 169

what 3 factors (genetic and otherwise) increase one's risk of cerebral vein thrombosis?

Back 169

FVL mutation, prothrombin mutation, OC's

Front 170

genetic contributions to increased risk of placental artery thrombosis

Back 170

FVL and prothrombin 20210G>A alleles

Front 171

what does placental artery thrombosis lead to?

Back 171

preeclampsia, premature separation of placenta from uterine wall, IUGR, stillbirth

Front 172

Recommendations for testing for FVL or prothrombin 20210G>A? (x7)

Back 172

1) VTE in someone <50yo 2) VTE in unusual sites 3) recurrent VTE 4) VTE and strong fam Hx of thrombotic dz 5) VTE in pregnant women or women taking OC's 6) relatives of individuals with VTE <50yo 7) MI in female smokers <50yo

Front 173

environmental factors that increase one's risk of VTE

Back 173

trauma, surgery, malignant disease, prolonged periods of immobility, OC use, advanced age known to increase risk of this

Front 174

Hirschsprung usually occurs in ____ of colon but can involve long continuous parts as part of ____

Back 174

short segment, syndrome (ex: Waardenburg-Shah syndrome)

Front 175

inheritance and recurrence risks for Hirschsprung disease

Back 175

AD or AR, recurrence risks not strictly 25 or 50%, risk ratio 200x for sibs but MZ twins not completely concordant

Front 176

Males have ____ risk of having Hirschsprung

Back 176

2x

Front 177

What 4 mutations can lead to Hirschsprung

Back 177

RET, GDNF, EDNRB, EDN3

Front 178

Penetrance in Hirschsprung is ___; sometimes requires both ___ and ___ mutations

Back 178

not complete, RET, GDNF

Front 179

MZ twins (one affected) have a ___% risk for developing type 1 DM? DZ twins?

Back 179

40% MZ, 5% DZ

Front 180

siblings with 2 haplotypes in common in type I DM have a ___% risk for developing DM? risk if DR3/DR4 is shared?

Back 180

17%, 20-25% if shared haplotype is DR3/DR4

Front 181

autoimmune destruction of beta cells in pancreas which normally produce insulin

Back 181

type 1 diabetes

Front 182

95% of all patients with type I diabetes are heterozygote for which HLA loci in the MHC gene?

Back 182

HLA-DR3 or HLA-DR4

Front 183

__ loci with aspartic acid at position 57 associated with resistance to type 1 diabetes

Back 183

DQB1

Front 184

90% of patients with type I DM are __alleles that do not encode Asp at position 57

Back 184

homozgous for DQB1

Front 185

Females are ____ often diagnosed with dementia or AD than males, and they are often Dx'd at ___ age

Back 185

more, >65yo

Front 186

most common cause of dementia in elderly and responsible for more than 50% of dementia cases

Back 186

Alzheimer disease

Front 187

death of cortical neurons that is progressive due to beta-amyloid plaques and neurofibrillary tangles, Dx'd postmorem, caused by cleavage of amyloid protein precursor

Back 187

Alzheimer Disease

Front 188

most significant risk factors for Alzheimer's disease

Back 188

age, gender, family hx

Front 189

Alzheimer DIsease has an MZ concordance of ___% and DZ __%

Back 189

50%, 18%

Front 190

individuals with FDR who has Alzheimer disease is at ___ more risk of developing this disease

Back 190

3-4x

Front 191

protein component of LDL particle and involved in clearing LDL through interaction with high-affinity receptors in liver

Back 191

APOE

Front 192

which allele increases one's risk for Alzheimer Disease the most?

Back 192

APOE E4 allele

Front 193

___% of all heterozygotes carrying one E4 allele in the APOE gene never develop disease

Back 193

50-75%

Front 194

Brain trauma interacts with the ___ allele in pathogenesis of Alzheimer disease

Back 194

E4

Front 195

Anencephaly and spina bifida frequently occur ____

Back 195

together in families

Front 196

___ of affected infants are females in anencephaly

Back 196

2/3

Front 197

fusion of arches of of vertebra (typically lumbar) with range of severity

Back 197

spina bifida

Front 198

TS 21 is seen more commonly in which gender?

Back 198

males (3:2)

Front 199

TS 18 and 13 are more commonly seen in which gender?

Back 199

female

Front 200

type of spina bifida with defect in bony arch only

Back 200

occulta

Front 201

type of spina bifida with bone defect associated with meningocele (protrusion of meninges) or meningomyelocele (protrusion of neural elements and meninges)

Back 201

aperta

Front 202

leading cause of stillbirth, death in early infancy, and handicap in surviving children

Back 202

spina bifida

Front 203

frequency of spina bifida varies with ___ and ___

Back 203

social factors and season of birth

Front 204

causes of spina bifida

Back 204

amniotic bands, single-gene defects with pleiotropic expression, some teratogens but most isolated

Front 205

supplementing with folic acid and continuing for 2 months after conception reduces incidence of spina bifida by more than ___%

Back 205

75%

Front 206

less than ___% of all patients with NTDs are born to women with previous affected child

Back 206

5%

Front 207

general population has a ___% risk of having a child with CL/P compared to __% if an FDR has CL/P

Back 207

0.1% 4%

Front 208

risk in siblings of proband with bilateral CL+P

Back 208

8%

Front 209

concordance of spina bifida among MZ twins? DZ twins?

Back 209

30%, 2%

Front 210

CL/P is due to failure of frontal process with maxillary process at ___ day of gestation

Back 210

35

Front 211

____% of those affected w/ CL/P are male

Back 211

60-80%

Front 212

2 types of syndromic cleft lip/palate

Back 212

trisomy 13, trisomy 4p-

Front 213

CL/P d/t 3 types of teratogenic exposure

Back 213

rubella embryopathy, thalidomide, anticonvulsants

Front 214

tethering of tongue by short or anterior frenulum

Back 214

ankyloglossia

Front 215

one example of single-gene defect leading to CL/P

Back 215

X-linked clefting with ankyloglossia

Front 216

there are 2 forms of single-gene AD clefting- one associated with missing ___ and other with __ and ___

Back 216

teeth, infertility, anosmia

Front 217

2 TF genes and one other gene leading to CL/P

Back 217

TBX1 and MSX1, FGFR1

Front 218

lower lip pits in 85% of patients, CL(P), webbing of skin from ischial tuberosities to heels, bifid scrotum and cryptorchidism, hypoplasia of labia majora, finger/toe syndactyly, nail bed anomalies, filliform synechiae connecting upper and lower jaws or eyelids, pyramidal fold of skin overlying nail of hallux pathognomonic

Back 218

Van der Woude syndrome

Front 219

gene mutation in Van der Woude syndrome

Back 219

IRF6

Front 220

what environmental factors have been proven to be associated with CL/P?

Back 220

maternal smoking

Front 221

congenital heart defects are seen in __ per 1000 births

Back 221

4-8

Front 222

what teratogens will cause congenital heart malformations?

Back 222

rubella, maternal diabetes

Front 223

When heart defects recur, doesn't have to be exactly the same but instead show recurrence of ___

Back 223

lesions similar in developmental mechanism

Front 224

25% of flow lesions in heart (especially tetralogy of Fallot) have which condition?

Back 224

22q11.2

Front 225

__% show familial aggregation of flow lesions in the heart?

Back 225

50%

Front 226

examples of flow lesions in heart

Back 226

hypoplastic left heart syndrome, coarctation of aorta, atrial septal defect of secundum type, pulmonary valve stenosis (common), tetralogy of Fallot

Front 227

relative risk to sibs greatest with which type of flow lesion in heart?

Back 227

aortic stenosis

Front 228

families with congenital heart defects other than flow lesions have what RR?

Back 228

no greater risk of recurrence than general population

Front 229

which mental illness has a 40-60% MZ concordance and 10-16% DZ concordance?

Back 229

schizophrenia

Front 230

Schizophrenia is seen in 25% of patients with which condition

Back 230

22q11.2

Front 231

which mental illness has a 62% MZ concordance risk and 8% DZ concordance and a 10-15% suicide rate?

Back 231

bipolar disease

Front 232

leading cause of morbidity and mortality in developed world

Back 232

coronary artery disease

Front 233

major cause of MI and deaths

Back 233

atherosclerosis

Front 234

Which gender is at 7x increased risk for CAD in population and affected families?

Back 234

males

Front 235

When proband is less than what age and has CAD does the risk for the family increase by 11.4x?

Back 235

<55yo

Front 236

Which condition accounts for 5% of MI survivors, is AD, and is an issue with the LDL receptor?

Back 236

familial hypercholesterolemia

Front 237

5 types of genes affecting CAD?

Back 237

1) LDL/HDL genes 2) ACE 3) blood coagulation genes 4) inflammatory and immune pathways 5) arterial wall components

Front 238

4 conditions where de novo mutations usually paternal in origin

Back 238

achondroplasia, craniosynostoses, MEN type 2 (A and B)

Front 239

3 conditions where increasing age of dad increases changces

Back 239

Apert, achrondroplasia, hemophilia B

Front 240

90% of all new point mutations for DMD are ___ in origin

Back 240

paternal

Front 241

chronic inflammatory disease of spine and sacroiliac joints

Back 241

ankylosing spondylitis

Front 242

95% of affected patients with ankylosing spondylitis are positive for which HLA allele?

Back 242

B27

Front 243

Sometimes, there is association due to particular MHC allele being present at a very high frequency on chromosomes that also happen to contain disease-causing mutation in another gene within MHC because of ____

Back 243

linkage disequilibrium

Front 244

>80% of patients with hemochromatosis are homozygous for a common mutation in the HFE gene (____) and have HLA-A*0301 alleles at HLA-___ locus

Back 244

Cys282Tyr, A

Front 245

gene encoding cell surface cytokine receptor serving as entry point for certain strains of HIV causing AIDs

Back 245

CCR5

Front 246

People homozygous for ___ allele don't express receptor on cell surface and are resistant to the HIV infection?

Back 246

Delta CCR5

Front 247

__% of affected people with hemophilia A have de novo mutations

Back 247

15%

Front 248

Treatment for hemophilia A is so good now that the proportion of hemophiliacs who will result from new mutations will ___ and the disease incidence ___

Back 248

decrease, won't change

Front 249

carrier frequency of sickle cell anemia in US African Americans

Back 249

1/11

Front 250

short-limbed dwarfism, polydactyly, abnormal teeth and nails, congenital heart defects, AR condition, product of founder effect

Back 250

Ellis-van Crevald syndrome in Old World Amish families

Front 251

hepatic failure, renal tubular dysfunction due to deficiency of fumarylacetoacetase, AR inheritance

Back 251

type I tyrosinemia

Front 252

100% of type I tyrosinemia found in Quebec is ____mutation from original founder

Back 252

same splice donor site mutation

Front 253

X-linked degenerative eye disease, 1/3 from small area of Finland

Back 253

choroideremia

Front 254

deficiency of ornithin aminotransferase and leading to loss of vision in young adulthood

Back 254

hyperornithinemia with gyrate atrophy of choroid and retina

Front 255

a chronic inflammatory disease of the GI tract primarily affecting adolescents and young adults, 2 subtypes

Back 255

IBD

Front 256

the 2 subtypes of IBD

Back 256

Crohn disease and ulcerative colitis

Front 257

What locus and gene has been associated with Crohn disease and NOT ulcerative colitis?

Back 257

IBD1 locus, NOD2 gene

Front 258

function of NOD2 protein

Back 258

binds to gram-negative bacterial cell walls and participates in inflammatory response to bacteria by activating NF-kappaB TF in mononuclear leukocytes

Front 259

The NOD2 variant is neither ___ nor ___ to cause Crohn disease

Back 259

necessary nor sufficient

Front 260

progressive degenerative disease of portion of retina responsible for central vision and causes blindness, >50yo, accumulation of EC protein deposits called drusen behind retina

Back 260

macular degeneration

Front 261

environmental factor that significantly increases risk of age-related macular degeneration

Back 261

cigarette smoking

Front 262

Which genetic alternation is responsible for 43% of all genetic contribution to age-related macular degeneration? What is its function?

Back 262

Tyr402His in the complement factor H protein, which regulates inflammation

Front 263

Which 2 genes protect AGAINST age-related macular degeneration?

Back 263

factor B and complement factor 2

Front 264

group of conditions d/t reduced or absent production of a globin mRNA from deletions or mutations in regulatory or splice sites of a globin gene

Back 264

thalassemias

Front 265

increased postnatal transcription of one or more gamma-globin genes

Back 265

hereditary persistence of fetal hemoglobin

Front 266

group of conditions due to nonfunctional or rapidly degraded mRNA's with nonsense or frameshift mutations

Back 266

thalassemias

Front 267

group of conditions d/t abnormal hemoglobins with aa substitutions or deletions leading to unstable globins that are prematurely degraded

Back 267

hemoglobinopathies

Front 268

a lysosomal storage disease d/t failure to add a phosphate group to mannose residues lysosomal enzymes (required to target enzymes to lysosomes), AR, facial features, skeletal changes, severe growth retardation, MR, and survive 5-7 years

Back 268

I-cell disease

Front 269

condition in which an aa substitution in a procollagen chain impairs the assembly of a normal collagen triple helix

Back 269

types of OI

Front 270

condition in which the C terminus of LDL receptor impairs localization of receptor to clathrin-coated pits, preventing internalization of receptor and subsequent recycling to cell surface

Back 270

familial hypercholesterolemia mutations (class 4)

Front 271

condition caused by poor or absent binding of cofactor (pyridoxal phosphate) to cystathionine synthase apoenzyme

Back 271

homocystinuria

Front 272

diseases in which mutant protein is normal in nearly every way except that one of its critical biological activities is altered by an aa substitution ex: Hb kempsey

Back 272

protein not correctly folded/assembled

Front 273

impaired subunit interaction locks hemoglobin into its high oxygen affinity state in this condition

Back 273

Hb Kempsey

Front 274

Hemoglobin is composed of ___ subunits: __ alpha and __ beta chains

Back 274

4, 2, 2

Front 275

Each subunit of hemoglobin is composed of ___, __ and ___

Back 275

polypeptide chain, globin, and prosthetic group (heme)

Front 276

Hemoglobin has ___ helical regions and ___ aa residues

Back 276

7-8, 2

Front 277

Alpha globin genes are on chromosome ___ and beta globin genes are on chromosome ___

Back 277

16, 11

Front 278

Hemoglobin is first made in the___ before 6 weeks gestation

Back 278

yolk sac

Front 279

Before birth and after 6 weeks gestation, where is hemoglobin made?

Back 279

liver and spleen

Front 280

After birth, where is hemoglobin made?

Back 280

spleen some until 6 weeks old and mostly bone marrow

Front 281

Which type of hemoglobin is made in the embryo

Back 281

Hb Gower and Hb Portland

Front 282

Which type of hemoglobin is made in the fetus?

Back 282

Hb F

Front 283

Which type of hemoglobins are made in the normal adult?

Back 283

Hb A2 and Hb A

Front 284

what will gene therapy focus on with beta thalassemia

Back 284

the LCR to change which globins are being made and how much

Front 285

Glu6Val mutation causes what disease?

Back 285

Hb S->sickle cell

Front 286

Glu6Lys mutation causes what disease?

Back 286

Hb C->Constant Spring

Front 287

example of an unstable hemoglobin

Back 287

Hb Hammersmith

Front 288

2 hemoglobins with altered oxygen transport

Back 288

Hb Hyde Park, Kempsey

Front 289

Hb E mutation causes what phenotype?

Back 289

mild

Front 290

What environment causes sickling in sickle cell anemia?

Back 290

deoxygenated blood

Front 291

issues with Hb C

Back 291

less soluble than Hb A, crystallizes in RBC's, reduces deformability in capillaries, causes mild hemolytic disease

Front 292

what leads to unstable hemoglobin?

Back 292

point mutations causing less affinity for oxygen and precipitate to form inclusions (Heinz bodies) contributing to damage of RBC membrane, cause hemolysis of mature RBC's in vascular tree; can cause cyanosis

Front 293

a type of deletion leading to transcription of antisense RNA silencing alpha2-globin gene

Back 293

ZF deletion

Front 294

alpha thalassemia and syndromic MR resulting from mutation in a gene on the X chromosome encoding chromatin remodeling protein required for normal expression of alpha-globin complex

Back 294

ATR-X syndrome

Front 295

fuction of ATRX chromatin remodeling protein

Back 295

activates expression of alpha-globin genes and others, establishes methylation; all mutations are LOF

Front 296

Myelodysplasia associated with alpha-thalassemia is caused by mutations in what gene?

Back 296

ATRX- alpha chain synthesis completely abolished (lethal if inherited)

Front 297

cause of symptoms in beta-thal

Back 297

decreased beta-globin production causing hypochromic, microcytic anemia and imabalance of globin synthesis leading to precipitation of excess alpha chains leading to damage of RBC membrane

Front 298

High Hb ___ and low Hb ___ in beta thal

Back 298

F, A

Front 299

Beta-+-thalassemia is having _____ while Beta-0-thal is having ___

Back 299

some Hb A, no Hb A

Front 300

beta thalassemia is usually caused by what kind of mutations?

Back 300

single bp substitutions

Front 301

no HbA present, severe anemia, lifelong medical management, infants have anemia once postnatal production of Hb F decreases (<2yo), red cell hypochromic and variable in size and shape, need blood transfusions, chelating agents, BM transplants

Back 301

beta thalassemia major

Front 302

The majority of beta thalassemia patients with a decreased abundance of beta-globin have mRNA abnormalities in ___

Back 302

RNA splicing

Front 303

if a nonfunctional mRNA is made due to a mutation in the beta globin gene, this generates a premature ____ codon and cause what type of beta thal?

Back 303

stop codon, beta-0-thalassemia

Front 304

if a frameshift occurs near the normal termination signal on the beta globin gene, ___ hemoglobin is created and phenotype is ___

Back 304

variant, mild

Front 305

process leading to reduction in abundance of mutant mRNA, leads to issues in nonsense codons located >50bp 5' to final exon-exon junction

Back 305

nonsense-mediated mRNA decay

Front 306

When you have defects in 5' cap and 3' polyA tail on the beta-globin gene, this leads to phenotype of ___

Back 306

beta-+-thalassemia

Front 307

Problems in Hb E variant

Back 307

mutant beta chain synethsized at reduced rate, creates a cryptic splice site, asymptomatic and mildly anemic phenotype

Front 308

Hb E is common in which alpha thalassemia mutation?

Back 308

SEA

Front 309

Type of thalassemia that removes beta-globin gene and one or more other genes (or LCR) from beta-globin cluster

Back 309

complex thalassemias

Front 310

how are complex thalassemias named?

Back 310

by genes deleted

Front 311

symptoms of hereditary persistence of fetal Hgb? Why?

Back 311

benign, no symptoms because Hb F synthesis at high level compensates for no Hb A

Front 312

Which country provides voluntary screening f/b testing of extended family once carrier identified and this dramatically reduced the birth rate of beta-thalassemic newborns?

Back 312

Sardinia

Front 313

which country found a small number of families had many affected people with thalassemia and found that 8% of married couples from these families were both carriers of beta thalassemia?

Back 313

Pakistan

Front 314

condition caused by a mutation in the ND1 protein of electron transport chain, causes rapid, painless bilateral loss of central vision due to optic nerve atrophy in young adults, increased penetrance for males (5:1)

Back 314

Leber hereditary optic neuropathy

Front 315

a condition caused by issues with tRNA

Back 315

MELAS

Front 316

a condition caused by issues with 12S RNA

Back 316

sensorineural deafness

Front 317

a condition caused by problems with 8 proteins functioning in the peroxisome

Back 317

Zellweger syndrome

Front 318

what gene mutation causes aniridia?

Back 318

Pax 6

Front 319

Gene mutation leading to classic, variant, and non-PKU phenotypes

Back 319

PAH

Front 320

Besides LOF mutation in the PAH gene, PKU can also be caused by mutations in genes responsible for synthesis and recycling of a cofactor ____

Back 320

BH4

Front 321

The enzyme that does not function anymore in PKU converts ___ to ____

Back 321

Phe, Tyr

Front 322

Why must Phe levels be taken after 1 day old to diagnose PKU?

Back 322

Phe levels increase after birth

Front 323

Treatment for positive PKU results must be done by ___ weeks old or permanent mental effects will occur

Back 323

4

Front 324

Phe levels when patient receiving normal diet for non-PKU hypherphe

Back 324

<1mM (1% or more PAH activity)

Front 325

__% of people with hereditary hyperphe actually have one defect in one of several diff genes involved in formation or recycling of cofactor of PAH, BH4

Back 325

1-3%

Front 326

What treatment is needed for PKU without mutation in PAH and instead issue with tetrahydrobiopterin metabolism?

Back 326

diet does NOT help, large doses of oral BH4 leads to reduction in plasma Phe AND administering products of tyrosine hydroxylase and tryptophan hydroxylase, L-dopa, and 5-hydroxytryptophan to normalize neurotransmitter levels

Front 327

PKU patients respond very well to diet and only partially to large doses of ___

Back 327

oral BH4 cofactor

Front 328

What can happen to a fetus if mom is affected with PKU and not on diet?

Back 328

cause MR, microcephaly, growth impairment and heart malformations

Front 329

lysosomal storage diseases lead to accumulation of substances inside lysosome resulting in ___ and ___

Back 329

cell dysfunction and cell death

Front 330

All lysosomal storage diseases progress if ____ and manifest clinically as increase in mass of ____

Back 330

not treated with ERT, of affected tissues and organs or neurodegeneration if in brain

Front 331

Tay Sachs is caused by ____ enzyme deficiency leading to an inability to degrade ___

Back 331

Hex A, spingolipid (GM2 ganglioside)

Front 332

Hex B deficiency leads to what condition

Back 332

Sandhoff disease

Front 333

3 mutations for Tay Sachs in AJ population account for ___% of cases

Back 333

99%

Front 334

A level of 20% Hex A is a ___

Back 334

pseudodeficiency

Front 335

MPS diagnosed early (<18 months), corneal clouding, skeletal changes, hepatosplenomegaly, coarse facies, death before 10yo

Back 335

Hurler

Front 336

All MPS conditions are due to AR inheritance except ___

Back 336

Hunter Syndrome

Front 337

MPS with onset >5yo, normal IQ and lifespan, corneal clouding, valvular heart disease

Back 337

Scheie

Front 338

MPS similar to Hurler, but with slower progression and mainly affects boys

Back 338

Hunter

Front 339

How are MPS conditions screened

Back 339

by looking at urine to see if GAGs (glycosaminoglycans) are present to prove they are not being degraded

Front 340

general MPS features

Back 340

MR, coarse facial features, skeletal abnormalities, short stature

Front 341

AR disease, defects in any number of genes regulating defense against infection and susceptible to disseminated infections on exposure to moderately virulent mycobacterial specials used as vaccine against TB or non-TB environmental bacteria that don't normally cause disease

Back 341

mendelian susceptibility to mycobacterial disease (MSMD)

Front 342

gene mutation seen in mendelian susceptibility to mycobacterial disease (MSMD)

Back 342

interferon-gamam receptor 2 (IFNGR2 mutation generating novel N-glycosylation site leading to large, overly glycosylated receptor

Front 343

Disorders that increase __-glycosylation are pathogenic just like N-glyscosylation disorders

Back 343

O

Front 344

cystathionine synthase deficiency, AR, dislocation of lens, MR, osteoporosis, long bones, thromboembolism of veins and arteries, Marfan phenotype

Back 344

homocystinuria

Front 345

treatment for homocystinuria

Back 345

large amounts of pyroxidine (vitamin precursor)

Front 346

Vitamin deficiencies can be partial or complete ___ of genetic disorder (ex: vegans acquiring B12 deficiency)

Back 346

phenocopy

Front 347

mehtionine synthase remethylates ____ to form methionine and loss of methionine synthase activity leads to ___

Back 347

homocysteine, homocystinuria

Front 348

inherited disorders of vitamin B12 transport or metabolism reduce availability of ____ and impair activity of methionine synthase

Back 348

methylcobalamin

Front 349

clinical phenotype of B12 deficiency

Back 349

methaloblastic anemia, DD, FTT

Front 350

enzymopathies are almost always what type of inheritance?

Back 350

AR

Front 351

Heterozygotes of enzymopathies usually have ___% of enzyme activity and this is usually enough to compensate

Back 351

50%

Front 352

which 2 enzymopathies are not AR inheritance?

Back 352

acute intermittent porphyria (AD) or Fabry Disease

Front 353

If substrate in an enzymopathy is small (ex: Phe), it can be readily distributed throughout bodily fluids by diffusion or transport which means disease phenotype is ___ and if it is large then it is confined to ____

Back 353

unpredictable, confined to tissue in which substrate accumulates

Front 354

Single gene defects can cause LOF in more than one enzyme because they use the same ___, the enzymes may share a common subunit or activating, processing or stabilizing ____, enzymes may be processed by a common modifying ___ and group of enzymes may be absent to ineffective if ___in which they are found ins not formed or is abnormal

Back 354

cofactor, protein, enzyme, organelle

Front 355

complete deficiency of purine enzyme hypoxanthine guanine phosphoribosyltransferase, causes hyperuricemia and profound neurological disease, self-aggressive behavior, resembles CP, hypotonia, DD by 3-6mo, build up of uric acid crystals in kidney, bladder, ureters, gouty arthritis, can live to 20-30's, carrier females can have hyperuricemia

Back 355

Lesch-Nyhan syndrome

Front 356

AR condition, associated with substantial risk of COPD and cirrhosis of liver as well as neonatal jaundice, effected by environmental issues

Back 356

AAT

Front 357

AD, intermittent neurological dysfunction, deficiency of prophobilinogen deaminase, enzyme in biosynthetic pathway of heme and alters regulation of genes controlling synthesis of heme, incomplete penetrance, abdominal pain and psychosis in crisis, muscle weakness, neuropathy, hepatocellular carcinoma, no cutaneous findings

Back 357

acute intermittent porphyria

Front 358

expression of acute intermittent porphyria based on environmental factors like ___, ___, and ___ states

Back 358

drugs (barbiturates), steroid hormones (after puberty/before menopause), and catabolic states (reducing diets, intercurrent illnesses and surgery)

Front 359

When certain environmental conditions are present in acute intermittent porphyria, synthesis of hepatic cytochromes ____ cause heme levels to ___ and reduce feedback inhibition of heme in heme synthesis pathways

Back 359

P450, fall

Front 360

4 gene products associated with familial hypercholesterolemia

Back 360

LDL receptor, Apoportein B-100, ARH adapter protein, PCSK9 protease

Front 361

All gene products mutated in familial hypercholesterolemia are ___ of function except ___

Back 361

loss, PCSK9 protease

Front 362

Normal adults have an LDL cholesterol level about ___ mg/dL, but those with familial hypercholesterolemia have up to ___mg/dL LDL level

Back 362

700 mg/dL

Front 363

All gene products associated with familial hypercholesterolemia are ___ inheritance except ___, which is ___ inheritance

Back 363

AD, ARH adaptor protein, AR

Front 364

Gene dosage is seen in familial hypercholesterolemia meaning_____

Back 364

homozygotes have more severe and earlier disease than hets (live until 30's and have disease in childhood)

Front 365

How does cholesterol uptake work in the LDL receptor?

Back 365

uptake of LDL through endocytosis leading to increased free IC cholesterol reduces endogenous cholesterol formation by suppressing rate-limiting enzyme of synthetic pathway. Increase in IC cholesterol reduces synthesis of receptor.

Front 366

Majority of mutations in LDL receptor are ___, ___, or ___. 2-10% are ___

Back 366

single nucleotide substitutions, small insertions, or deletions, structural rearrangements

Front 367

Most common type of disease-causing mutation at the LDL receptor locus?

Back 367

null alleles preventing synthesis of any detectable receptor

Front 368

Besides null alleles in the LDL receptor locus, the receptor is synthesized ___, but function ___

Back 368

normally, impaired (transport-deficient, incapable of binding LDL, remove C terminus of receptor, recycling-defective alleles)

Front 369

Mutations in PCK9 do what?

Back 369

increased protease activity leads to degradation of LDL receptor regulating level of receptor in haptocytes

Front 370

Excess cholesterol from familial hypercholesterolemia stored as ___ droplets, producing foam cell appearance seen in ___ and ___

Back 370

cholesteryl ester, xanthomas, atherosclerotic plaques

Front 371

50% of CF patients survive until ___yo and usually die from ___

Back 371

33, pulmonary infection and failure

Front 372

condition with thick secretions, recurrent infections, chronic obstructive lung disease, maldigestion, pancreatic insufficiency, meconium ileus in newborns, reduction of fertility or total infertility

Back 372

CF

Front 373

cause of CFTR symptoms

Back 373

LOF in CFTR means chloride in duct of sweat gland can't be reabsorbed leading to reduction in electrochemical gradient normally driving sodium entry across apical membranes leading to increased chloride and sodium in sweat and mucus layer adherent to cell surfaces

Front 374

Delta F508 mutation accounts for ___% of cases with CF

Back 374

70

Front 375

CFTR genotype is a good predictor of ____ and poor predictor of ___

Back 375

exocrine pancreatic function, severity of pulmonary disease

Front 376

Universal screening for CF carriers should not be done until we can detect ___% of the mutations for all ethnicities

Back 376

90

Front 377

symptoms female carriers of DMD have

Back 377

70% elevated CK levels, 19% some muscle weakness, 8% CM and proximal muscle disability (X-inactivation skewing/X-autosome translocation or TS)

Front 378

BMD account for ___% of mutations in the DMD gene and has __% fitness so a large amount of BMD is inherited and __ de novo

Back 378

15%, 70%, 10%

Front 379

Muscle weakness, walking until 16yo, express some dystrophin but not normal levels, CK levels elevated, more mild phenotype than DMD

Back 379

BMD

Front 380

function of dystrophin

Back 380

anchors a large protein complex at cell membrane, maintenance of muscle membrane integrity by linking actin cytoskeleton to EC matrix, position proteins in complex so they function correctly, contain ion channels and signal molecules for cell-cell substratum recognition

Front 381

60% of DMD or BMD mutations are ___, 34% are ___ and 6% are ___

Back 381

gene deletion, point mutations, partial duplication

Front 382

3 reasons a female would be affected with DMD with one mutated dystrophin gene

Back 382

nonrandom X-inactivation, Turner Syndrome, X-autosome translocation

Front 383

severe skeletal abnormalities (fractures, deformities), dark sclerae, death within 1 month, production of type I collagen abnormal, AD inheritance, perinatal lethal

Back 383

type II OI

Front 384

fractures often at birth, progressive bone deformity, limited growth, blue sclerae, AD inheritance, abnormal type I collagen

Back 384

type III OI

Front 385

normal sclerae, mild to moderate bone deformity, short stature, fractures, abnormal type I collagen, AD inheritance

Back 385

type IV OI

Front 386

90% of patients with OI have mutations in ___ and ___

Back 386

COL1A1 and COL1A2

Front 387

Type I procollagen molecules must have 2 ____ chains and loss of half mRNA leads to production ___ quantity of type I procollagen molecules but these molecules are normal

Back 387

proalpha1(I), half normal

Front 388

Most mutations leading to diminished amount of type I collagen due to ____ in COL1A1 allele rendering mRNA from that allele highly unstable

Back 388

premature termination codons

Front 389

Missense mutations in the A terminus when aa is changed in COLA1A1 give rise to what type of phenotype in OI?

Back 389

milder

Front 390

Substitutions in the proalpha1(I) chain are more prevalent in patients with OI type ___ and ___ and are more often lethal

Back 390

III, IV

Front 391

OI types __, ___, __ don't result from mutations in type I collagen genes but instead are on chromosome 3 and are ___ inheritance. Phenotype is similar to OI type ___.

Back 391

V, VI, VII, AR, IV

Front 392

Why do structurally defective proalpha1(I) chains cause so much more severe symptoms?

Back 392

impair contribution of both normal proalpha1 chains and normal proalpha2 chains leading to effect being amplified d/t polymeric nature of collagen molecule

Front 393

For OI, it's better phenotypically to have a mutation generating ___ gene product than ___ product

Back 393

no, abnormal

Front 394

OI type ___ can be seen on ultrasound in the second trimester

Back 394

II

Front 395

possible treatment for OI

Back 395

bisphosphonates

Front 396

Name the gene and the condition associated with mutations in it: transmembrane protein found in endosomes, lysosomes, ER, and golgi; produces principal component of senile plaques

Back 396

APP, Alzheimer disease

Front 397

4 Genes involved in susceptibility to Alzheimer disease

Back 397

APP, PSEN1, PSEN2, APOE

Front 398

Name the gene and condition: may participated in abnormal cleavage of beta APP, protein found in brain

Back 398

PSEN1, alzheimer disease

Front 399

maximal expression outside brain, contribute to Alzheimer disease, age of onset variable because based on APOE E4 alleles

Back 399

PSEN2

Front 400

A mutation in which gene leads to a 50% risk to family members having Alzheimer disease?

Back 400

PSEN1

Front 401

Which haplotype of APOE contributes to 30-50% of genetic risk of Alzheimer?

Back 401

E4

Front 402

onset in 60's-90's or if early-onset in 30's, progressive deterioration of memory and higher cognitive functions due to degeneration of neurons in cerebral cortex and hippocampus

Back 402

Alzheimer Disease

Front 403

Alzheimer disease is caused by deposition in the brain of which 2 proteins?

Back 403

beta-amyloid peptide and tau protein

Front 404

microtubule-associated protein expressed abundantly in neurons of brain, hyperphosphorylated forms of this compose neurofibrillary tangles found within neurons of people with Alzheimer Disease

Back 404

tau

Front 405

mutations in tau gene are associated with what 2 conditions?

Back 405

AD dementia, frontotemporal dementia

Front 406

Which type of peptide occurring from amyloid precursor protein is neurotoxic?

Back 406

abeta42

Front 407

In autosomal dominant Alzheimer Disease, __ peptide is selectively increased in production and leads to accumulation.

Back 407

Abeta42

Front 408

Why is it that people with ts 21 develop Alzheimer disease and early?

Back 408

betaAPP is on chromosome 21, so possessing 3 copies of this gene causes this phenotype

Front 409

protective allele on APOE gene for Alzheimer disease

Back 409

E2

Front 410

Carriers of E4 alleles on APOE gene have poorer neurological outcomes after ____

Back 410

head injury or stroke

Front 411

mitochondrial NADH dehydrogenase subunit 1, 4, 6 mutations, some recovery of vision, more males have visual loss than females, maternal inheritance

Back 411

Leber hereditary optic atrophy

Front 412

neuropathy, ataxia, RP, DD, MR, lactic acidemia, mutation in ATPase subunit 6 gene, maternal inheritance

Back 412

NARP

Front 413

early-onset progressive neurodegeneration of inferior brain structures like basal ganglia/cerebellem/brainstem with hypotonia, DD, optic atrophy, respiratory abnormalities, ATPase subunit 6 gene, maternal inheritance, mutations in nuclear-encoded complex 1,2, and 4 and mtDNA complex 5 gene

Back 413

Leigh Syndrome

Front 414

myopathy, mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes, DM, deafness, tRNA mutation 3243A>T, maternal inheritance

Back 414

MELAS

Front 415

myoclonic epielepsy with ragged red fibers, myopathy, ataxia, SNHL, dementia, tRNA mutation 8344A>G, maternal inheritance

Back 415

MERRF

Front 416

progressive atrophy of extraocular muscle, ptosis, common MELAS point mutation in tRNA, maternal inheritance or sporadic,

Back 416

chronic progressive external opthalmoplegia (CPEO)

Front 417

pancreatic insufficiency, pancytopenia, lactic acidosis, KSS (Kearns-Sayre Syndrome) in second decade, generally sporadic and due to somatic mutations (large deletions)

Back 417

Pearson syndrome

Front 418

progressive myopathy, progressive external opthalmoplegia of early onset, CM, heart block, ptosis, retinal pigmentation, ataxia, diabetes, generally sporadic, due to somatic mutations, onset <20yo, 1+ of cardiac conduction defect, ataxia, CSF protein>100, abnormalities of brain/heart/renal tubules/endocrine glands

Back 418

Kearns-Sayre Syndrome (KSS)

Front 419

mtDNA genome mutates at ___x the rate of nuclear DNA

Back 419

10

Front 420

Most mitochondrial conditions are ____ (phenotype)

Back 420

neuromuscular

Front 421

3 types of mutations seen in mtDNA

Back 421

1) missense in coding regions altering activity of oxidative phosphorylation protein 2) point mutations in tRNA or rRNA genes impairing mitochondrial protein synthesis 3) rearrangements generating del/dups of mtDNA molecule

Front 422

# of mtDNA molecules within each oocyte reduced before being subsequently amplfied to huge total seen in mature oocytes

Back 422

mitochondrial genetic bottleneck

Front 423

2 causes of phenotype in mitochondrial conditions?

Back 423

decreased atp production and generation of reactive O1 species

Front 424

neuromuscular phenotype in mitochondrial conditions

Back 424

encephalopathy, myopathy, ataxia, retinal degeneration, LOF of external ocular muscles

Front 425

general phenotype in mitochondrial conditions

Back 425

liver dysfunction, BM failure, pancreatic islet cell deficiency and DM, deafness, other disorders

Front 426

critical threshold in proportion of mtDNA molecules carrying detrimental mutations must be exceeded in cells from affected tissue before clinical disease becomes apparent

Back 426

phenotypic threhold

Front 427

mutation in an RNA gene in nuclear genome (only one to date) and conditions it causes

Back 427

RMRP gene mutations- encode untranslated RNA subunit of ribonucleoprotein endoribonucleas RNase MRP and causes 3 different short stature syndromes including AR cartilage hair hypoplasia

Front 428

mtDNA has been called "slave of nuclear DNA" because mtDNA ____

Back 428

depends on many nuclear-genome encoded proteins for replication and maintanence of integrity

Front 429

mutations in any of 6 nuclear genes leading to reduction in number of copies of mtDNA in various tissues, myopathic and hepatocerebral phenotypes result from mutations in genes for mitochondrial thymidine kinase and deoxyguanisine kinase

Back 429

mtDNA depletion syndrome

Front 430

mutations in thymidine phosphorylase, important for maintenance of mitochondrial nucleotide pools, blood thymidine levels increased

Back 430

mitochondrial gastrointestinal encephalomyopathy

Front 431

protein encoded by a gene deletion autosomally transmitted in mtDNA and helps in DRNA primase or helicase

Back 431

twinkle

Front 432

mutation in twinkle leads to phenotype resembling ___

Back 432

CPEO

Front 433

Penetrance in LHON is greater for which gender? Why?

Back 433

males because penetrance is determined by Xp haplotype and this modifies phenotype

Front 434

Why are repeated sequences in HD different than those in FX, Friedrich ataxia, and myotonic dystrophy?

Back 434

HD sequences are in transcribed region of affected gene and others are in noncoding regions of RNA

Front 435

repeat expansion in myotonic dystrophy type 2

Back 435

CCTG

Front 436

repeat expansion in spinocerebellar atrophy type 10

Back 436

ATTCT

Front 437

most common inherited spinocerebellar ataxia?

Back 437

freidreich ataxia

Front 438

2 examples of diseases due to expansion of noncoding repeats causing loss of protein function by impairing transcription of preRNA from an affected gene

Back 438

FX, Freidreich ataxia

Front 439

Brains of people with FX have increased density and abnormally long ___ and ___ protein localizes here, where its role is to regulate synaptic ___

Back 439

dendritic spines, FMRP, plasticity

Front 440

3 conditions that result from expansion in non-coding repeats that confer novel properties on RNA

Back 440

myotonic dystrophy type 1 and 2, FXTAS

Front 441

Same symptoms as type 1 myotonic dystrophy but without congenital form, also AD inheritance

Back 441

type 2 myotonic dystrophy

Front 442

treatment (surgical and otherwise) for biotinidase deficiency prenatally?

Back 442

maternal biotin administration or percutaneous catheter/vesicostomy for hydronephrosis

Front 443

treatment (surgical and otherwise) for Vit B12-responsive methylmalonic aciduria prenatally?

Back 443

maternal vit B12 administration or fetal tracheal occlusion by balloon for diaphragmatic hernia

Front 444

treatment (surgical and otherwise) for CAH prenatally?

Back 444

dexamethasone to mom or fetoscopic laser ablation of communicating placental vessels

Front 445

PEG-ADA success shows that proteins ____ to improve effectiveness and enzyme normally located in cell can be effective in ___ fluid its product can be ____

Back 445

can be modified, EC, taken up by cells that require it

Front 446

2 problems with ERT

Back 446

1) can't pass BBB yet 2) expensive

Front 447

AR inheritance, deficiency of enzyme glucocerebrosidase leading to accumulation, enlargement of liver and spleen, BM replaced by lipid-laden macrophages, anemia, thrombocytopenia, bone lesions, osteonecrossis,

Back 447

Gaucher disease

Front 448

how does glucocerebroside ERT work?

Back 448

modify carbs on glycoprotein by removing terminal sugars to expose core alpha-mannosyl residues which target enzyme to macrophage then once bound to lysosome

Front 449

AD inheritance, mutations in gene encoding complement 1 (C1) esterase inhibitor, unpredictable episodes of varying severity of submucosal and subcutaneous edema and when involving upper respiratory tract are fatal

Back 449

hereditary angioedema

Front 450

hereditary angioedema requires long-term prophylaxis with attenuated androgens and is an example of what therapy?

Back 450

increasing amount of mRNA from wild-type locus associated with dominant disease or from mutant locus if mutant protein retains some function

Front 451

drugs for sickle cell and beta-thal that induce DNA hypomethylation and increase abundance of Hgb F are examples of what therapy?

Back 451

increasing expression of normal gene that compensates for effect of mutation at another locus

Front 452

mutations in X-linked gene encoding gamma-cytokine receptor subunit of interleukin receptors, causes block in T- and natural killer lymphocyte growth, survival and differentiation

Back 452

X-linked SCID

Front 453

treatment of X-linked SCID with gene therapy resulted in dramatic clinical improvement, but may have resulted in ___

Back 453

leukemia like disorder from vector insertion into LMO2 locus on chromosome 11 leading to aberrant T-cell expression

Front 454

No evidence of leukemic transformation using gene therapy in this type of SCID

Back 454

ADA

Front 455

condition caused by LOF mutations in gene for TF GLI3 causing distal end of human upper limb bud to develop into a hand with 5 digits, macrocephaly, frontal bossing, hypertelorism, polydactyly with broad thumbs and hallices, agenesis of CC, syndactyly

Back 455

Greig cephalopolysyndactyly

Front 456

condition consisting of contractions of joints of extrimities with deformation of developing skull sometimes due to constraint of fetus from twin or triplet gestations or prolonged leakage of amniotic fluid

Back 456

arthrogyposis

Front 457

partial amputation of fetal limb associated with strands of amniotic tissue, partial and irregular digit amputations with constriction rings seen

Back 457

amnion disruption

Front 458

Chromosomal imbalance accounts for ___% of malformations of which chromosomes ___, ___, and ___ are most common

Back 458

25%, 21, 18, 13

Front 459

branchial arch defect leading to issues with development of ear/neck/renal anomalies caused by mutations in EY1 gene, encoding protein phosphatase functioning in ear and kidney development, SNHL or mixed HL, branchial fistulae and cysts

Back 459

branchio-oto-renal dysplasia syndrome

Front 460

LOF in transcriptional coactivator resulting in abnormalities in transcription of many genes depending on this coactivator being present in a transcription complex for normal expression

Back 460

Rubenstein-Taybi

Front 461

U-shaped cleft palate and small mandible d/t restriction of mandibular growth before 9 weeks gestation causing tongue to lie more posteriorly interfering with normal closure of palatal shelves causing cleft palate; can be isolated or d/t extrinsic impingement on developing mandible by twin in utero

Back 461

Robin sequence

Front 462

Robin sequence can be one of features in this condition; mutation in gene encoding subunit of type II collagen resulting in abnormally small mandible, stature, joint, and eye defects, midface hypoplasia, myopia, glaucoma, cataracts, retinal detachment, HL can progress over time, hypermobility then arthritis and scoliosis/kyphosis, platyspondyly

Back 462

Stickler syndrome

Front 463

condition seen in fetuses of pregnant women who took isotretinoin during pregnancy, mimics action of endogenous retinoic acid causing them to follow particular (incorrect) development

Back 463

fetal retinoid syndrome

Front 464

condition caused by teratogen that leads to malformed limbs in fetuses exposed between 4-8 weeks gestation d/t effect on vasculature of developing limb buds

Back 464

thalidomide syndrome

Front 465

condition cause by teratogen leading to certain facial characteristics like microcephaly as well as moderate ID which only occurs during certain time of exposure in pregnancy when brain and face developing

Back 465

fetal alcohol syndrome

Front 466

condition caused by LOF of one of 2 protein components of primary cilia, polycystin 1 or 2, so cells fail to send fluid flow in kidney and continue to proliferate and don't undergo appropriate developmental program of polarization in which they stop dividing and display polarized expression of certain proteins on apical or basal aspect of tubular epithelial cells, continued cell division leads to cyst

Back 466

Polycystic kidney disease

Front 467

condition caused by 17p contiguous gene deletion syndrome involving LIS1 gene, LOF, waves of migration of cortical neurons don't occur so thickened hypercellular cerebral cortex with undefined cell layers and poorly developed gyri results, profound MR, smooth brain (lissencephaly)

Back 467

Miller-Dieker Syndrome

Front 468

Hirscshprung disease is due to a failure of migration of ____ cells to the gut

Back 468

neural crest cells

Front 469

Which gene deletion in DiGeorge syndrome may lead to issues with apoptosis like eliminating lymphocyte lineages that react to self preventing autoimmune disease

Back 469

TBX1

Front 470

2 conditions caused by GLI3 TF gene mutation and limb, CNS, craniofacial, airway, and GU anomalies,

Back 470

greig cephalopolysyndactyly syndrome (GCPS), Pallister-Hall Syndrome

Front 471

mutations in PTCH1 leading to ___ syndrome with craniofacial anomalies and occasional polydactyly and dental cysts with basal cell carcinomas

Back 471

Gorlin

Front 472

Mutations in the CREB binding protein, a transcriptional activator of GLI3 TF leads to a phenotype with GCPS and Gorlin- a condition called ___

Back 472

Rubenstein-Taybi

Front 473

Maternal treatment for prenatal CAH

Back 473

glucocorticoid, prevents pseudohermaphroditism and improves fetal development

Front 474

maternal treatment for prenatal Vit B12-responsive methylmalonic acidemia

Back 474

administration of B12

Front 475

Fetal surgery for Potter syndrome

Back 475

shunting for severe fetal bladder outlet obstruction preventing irreversible damage to lungs and postnatal renal function

Front 476

fetal procedure for SCID

Back 476

prenatal BM transplant with haploidentical donor

Front 477

AD inheritance, high incidence of medullary thyroid carcinoma, pheos, benign parathyroid adenomas or both, mutation in RET gene

Back 477

MEN type A

Front 478

medullary thyroid carcinoma of thyroid, pheos, benign parathyroid adenomas, neuromas on mouth and lips, RET gene mutation, AD inheritance

Back 478

MEN type B

Front 479

Normal functioning of which gene is required for normal development of autonomic ganglia and kidneys

Back 479

RET

Front 480

upslanting palpebral fissures, epicanthal folds, brushfield spots in eyes, microcephaly, brachycephaly, flat nasal bridge, small dysplastic ears, large tongue and small mouth, excess nuchal skin, hypotonia, short stature, short fingers, fifth-finger clinodactyly, sandal gap, single palmar crease, VSD/ASD/endocardial cushion defects, GI atresia, HL, nystagmus, strabismus, hypothyroidism, acquired hip dislocation, Alzheimers, leukemia, transient myeloproliferative disorder as newborn

Back 480

Trisomy 21

Front 481

sex ratio of trisomy 21?

Back 481

3 male: 2 female

Front 482

___% of TS 21 due to unbalanced robertsonian translocation

Back 482

3-4%

Front 483

___% of TS 21 mosaic with normal cell line

Back 483

1-2%

Front 484

most common Robertsonian translocation leading to TS 21

Back 484

14;21 translocation: 46,X_,der(14;21)(q10;q10)

Front 485

At least __ of phenotypically normal offspring of a 14;21 carrier will be carriers themselves

Back 485

50%

Front 486

deafness, seizures, apneic spells, holoprosencephaly, hypotonia, microcephaly, micropthalmia, CL/P, micrognathia, colobomata, low-set ears, hypotelorism, clubfoot, polydactyly, VSD/PDA/coarctation, omphalocoele or umbilical hernia, polycystic kidneys, scalp defect, hemangiomata, cryptorchidism, bicornuate uterus

Back 486

Trisomy 13 (Patau Syndrome)

Front 487

Which gender is seen more frequently with TS 13?

Back 487

females

Front 488

Which Robertsonian translocation can cause trisomy 13?

Back 488

13;14

Front 489

13;14 translocations are seen in ___% of Patau Syndrome?

Back 489

20%

Front 490

Empiric risk of having a liveborn child with TS 13 in a parent with a 13;14 balanced translocation?

Back 490

1%

Front 491

most common translocation seen in human population

Back 491

13;14

Front 492

M:F ratio of babies with TS 18?

Back 492

M:F ratio 1:3

Front 493

MR, hypotonic in newborn period then hypertonicity, prominent occiput, small palpebral fissures, small mouth, low-set malformed ears, micrognathia, overlapping fingers, rocker bottom feet, hirsutism, cardiac anomalies

Back 493

trisomy 18

Front 494

Empiric recurrence risk for women under 30yo who had child with trisomy 21 is 1-2% and is also increased for all ____

Back 494

nondisjunction-type chromosomal abnormalities

Front 495

most frequently observed trisomy in SAB and thus most common autosomal trisomy in humans, mosaics may be liveborn

Back 495

trisomy 16

Front 496

non-mosaic autosomal trisomies seen postnatally besides 21 and 18?

Back 496

8,9,22

Front 497

profound MR, seizures, sparse hair in temporal areas, coarse facial features in older patients, abnormality found in fibroblasts but NOT blood d/t tissue limited mosaicism, hypotonia in infancy and childhood, high rounded forehead, broad nasal bridge, short nose, hypertelorism, low-set ears, round cheeks, wide mouth with thin upper lip, large tongue, CP, HL, vision impairment, seizures, extra nipples, genital abnormalities, heart defects, polydactyly, large big toes, short limbs, diaphragmatic hernia

Back 497

Pallister-Killian (i(12p))

Front 498

Prenatal diagnosis de novo SMC associated with abnormal phenotype ___% of the time

Back 498

13-16%

Front 499

If de novo SMC is derived from nonacrocentric chromosomes, the risk is ___% for an abnormal phenotype compared to ___% for acrocentric chromosome marker

Back 499

28.6% v. 7-11%

Front 500

1 in ___ liveborn children have sex chromosome abnormalities

Back 500

1/500

Front 501

hypothesis about x-chromosome inactivation/dosage compensation

Back 501

Lyon Hypothesis

Front 502

X-inactivation occurs ____ and is irreversible in somatic cells and all descendents of that cell will have same X inactivated

Back 502

early in embryogenesis

Front 503

darkly staining chromatin can be seen in non-dividing cells with more than one X chromosome

Back 503

Barr bodies

Front 504

25% of mosaic Turner Syndrome patients (5-6% of all patients with TS) will have a Y-bearing cell line and can present with external genitalia and a 15-20% risk of ___ or ___

Back 504

gonadoblastoma or ambiguous genitalia

Front 505

Where is the X-chromosome critical region leading to increased risk for gonadal dysgenesis when broken

Back 505

Xq 13-Xq26 (excluding Xq22

Front 506

In females with one normal X and one abnormal X as part of an unbalanced arrangement, there will be preferential inactivation of which X?

Back 506

abnormal X, resulting in milder phenotype

Front 507

In females with balanced X-autosome translocations, will usually have which X inactivated?

Back 507

normal X

Front 508

Males with balanced rearrangements of X will often have what phenotype?

Back 508

infertile, genital abnormalities

Front 509

Extreme skewing of XCI may contribute to ___fetal outcome in trisomy rescue cases

Back 509

poor

Front 510

most frequent cause of hypogonadism and infertility in males

Back 510

Klinefelter

Front 511

cardiovascular pedigree clues

Back 511

 Palpitations/arrhythmias, c/w unusually chest pain or SOB during exercise, heart failure (SOB, edema, fatigue), congenital heart disease, HTN, heart murmur, DVT, heart/lung transplant or surgery, enlarged heart, pacemaker/ICD, congenital deafness, MI/CAD >40yo or <40yo, stroke/tia > or <60yo, sudden unexplained death (SIDS, odd/unexplained accidents like single car accident and driver alone in middle of day, >40yo or <40yo healthy and no physical cause identified), fainting/black-out/near fainting (context? Trigger?- exercise/rest, medication, postpartum), seizures, dizziness

Front 512

heart issues and numbness/tingling with heat/cold intolerance suggests what condition?

Back 512

Fabry

Front 513

heart issues and arachnodactyly, dislocated lens suggests what condition?

Back 513

Marfan

Front 514

early onset condition presenting with overwhelming lactic acidosis in first hours after birth leading to multi-system failure and death, often congenital anomalies esp. brain and kidneys (cysts), neurocognitive disease, carbohydrate-induced ataxia, pyruvate dehydrogenase complex deficiency

Back 514

X-linked E1 alpha deficiency

Front 515

most common clinical manifestations of a mitochondrial disease?

Back 515

migraine, depression, bowel dysmotility

Front 516

malignant migraine/stroke-like episode, myopathy, encephalopathy, lactic acidosis, commonly caused by 3243A>G point mutation in tRNA-leu^UUR

Back 516

MELAS

Front 517

most common mtDNA disorder

Back 517

leber hereditary optic neuropathy (LHON)

Front 518

rapid visual loss in 2nd/3rd decades, low penetrance, 4x more common in males, most commonly caused by mtDNA in complex 1 genes

Back 518

LHON (leber hereditary optic neuropathy)

Front 519

Children with what diagnosis are more likely to have mitochondrial dysfunction, mtDNA overreplication, and mtDNA dels than typically developing children?

Back 519

autism

Front 520

sensorineural deafness, dystonia, dysphagia, cortical blindness, paranoia, X-linked, mutations in DDP1, involved in mitochondrial protein import

Back 520

Mohr-Tranebjaerg syndrome

Front 521

proteins involved in outer membrane mitochondrial fusion

Back 521

mitofusins Mfn1 and Mfn2

Front 522

proteins involved in inner membrane mitochondrial fusion

Back 522

OPA1

Front 523

mutations in OPA1 cause what condition?

Back 523

hereditary optic atrophy

Front 524

mutations in Mfn2 causes what condition?

Back 524

CMT 2A

Front 525

What protein participates in synthesis and maintenance of iron-sulfer clusters present in complexes I-III of respiratory chain and aconitate in Krebs cycle, leads to mitochondrial iron overload and mitochondrial dysfunction when mutated

Back 525

frataxin (in Friedreich ataxia)

Front 526

Alzheimer, Parkinson, and ALS all have a ___ component in their pathology similar to Friedreich ataxia.

Back 526

mitochondrial

Front 527

ocular myopathy without systemic disease, adult onset, mutations in ANT-1 and C10orf2 in mtDNA

Back 527

progressive external opthalmoplegia (PEO)

Front 528

mitochondrial neurogastrointestinal encephalomyopathy, disorder of inter-genomic communication, AR mutations in thymidine phosphorylase in ECGF1, ANT1 and POLG; adult onset, GI disease including diarrhea and pseudoobstruction

Back 528

MGNIE

Front 529

very low mtDNA copy number per cell, infantile neuromuscular and/or hepatic failure a result, disorder of inter-genomic communication, mutations in POLG and C10orf2, ECGF1, SUCLA2, MPV17; antiretroviral drugs can help

Back 529

mtDNA depletion

Front 530

gene that replicates and proofreads mtDNA; mutations associated with AR PEO with or without PD, AR PEO with or without parkinsonism, Alpers syndrome, SANDO, male subfertility, premature menopause, and cataracts

Back 530

POLG

Front 531

sensory ataxia, neuropathy, dysarthria, opthalmoplegia

Back 531

SANDO

Front 532

psychomotor regression with hepatic cirrhosis, usually with infantile onset

Back 532

Alpers syndrome

Front 533

3243 A>G mutation associated with what mitochondrial condition?

Back 533

MELAS

Front 534

8344A>G associated with what mitochondrial condition?

Back 534

MERRF

Front 535

8993G>T or G>C mutations associated with which 2 mitochondrial conditions

Back 535

NARP, maternally inherited Leigh Syndrome

Front 536

neuropathy, ataxia, retinitis pigmentosa

Back 536

NARP

Front 537

1555A>G mutations associated with that mitochondrial condition?

Back 537

maternally inherited deafness

Front 538

what general category of condition would you think of with symptoms that are multiple, functional, transient or intermittent, cluster into "episodes", present during viral illness or fasting

Back 538

mitochondrial

Front 539

clinical manifestations of mitochondrial conditions in general

Back 539

idiopathic disease, 2+ neuromuscular/endocrine/renal tubular disease manifestations, transient/intermittent, complicated migraine/stroke/seizures/dysautonomia/myopathy/loss of milestones/ataxia/tremor/HL/retinal disease, LD, psychiatric disease, SIDS

Front 540

Lactate for metabolic diagnostic testing has ___ sensitivity and specificity

Back 540

low

Front 541

urine organic acids for metabolic diagnostic testing has ___ sensitivity on ___ samples

Back 541

good, stress/ill samples

Front 542

frontal bossing, high arched palate, prognathism, pointed chin, large ears, overgrowth (return to normal in adulthood), DD, deletion of NSD1 gene

Back 542

Sotos

Front 543

submicroscopic deletion ~500kb in size, associated with inversion polymorphism, MAPT gene involved, phenotype: MR, hypotonia, friendly behavior, brain anomalies, distinct facial features, low birthweight, poor feeding in neonatal period

Back 543

del(17)(q21.31)

Front 544

most common microdeletion syndrome

Back 544

DiGeorge Syndrome

Front 545

severity of phenotype ____ correlate with size of deletion or position of breakpoints

Back 545

does NOT

Front 546

Most of 22q11.2 deletions are ___ with __ recurrence risk

Back 546

94%, very low (<1%)

Front 547

3 neuropsychiatric disease picked up by array?

Back 547

Alzheimer disease, PD, schizophrenia

Front 548

detection rate in patients with ID, ASD, or DD with conventional cytogenetics? FISH? oligo or SNP whole genome array?

Back 548

5-10%, 0.5-7%, 15-20%

Front 549

BLM helicase interacts with what protein?

Back 549

topoisomerase III

Front 550

FV Leiden is a ___ of function mutation

Back 550

gain

Front 551

a loss of function mutation in the factor V causes ___

Back 551

hemorrhagic disease

Front 552

G1691A mutation causes ____

Back 552

FVL

Front 553

CAG expansion is seen in what conditions?

Back 553

SCA, Machado-Joseph, HD, DRP atrophy, spinal and bulbar atrophy (Kennedy disease)

Front 554

recombination rate within DMD

Back 554

12% (5x normal)

Front 555

difference between Duchenne v. Becker mutations

Back 555

Duchenne has out-of-frame deletions and Becker has in-frame deletions leading to some production of proteins just shortened

Front 556

DMD mutation rate

Back 556

1/10,000 eggs and sperm

Front 557

which proteins interact with dystrophin and thus can cause muscular dystrophy

Back 557

laminin (AR congenital muscular dystrophy + white matter) and sarcoglycans (4+, AR, clinically like BMD and DMD)

Front 558

what abnormalities in dystrophin are seen in DMD v. Becker

Back 558

DMD: dystrophin absent, Becker: smaller molecular weight/reduced in quantity

Front 559

if proband's mom is deletion positive for DMD, then ___% chance mom is a carrier of DMD

Back 559

100%

Front 560

if proband is deletion positive for DMD and mom is deletion negative then ___% chance mom is a carrier and recurrence risk is ____

Back 560

0%, >0% d/t gonadal mosaicism

Front 561

if proband is deletion positive and mom is not a carrier, ___% recurrence risk to an at-risk X? to next pregnancy? to next male pregnancy?

Back 561

20%, 5%, 10%

Front 562

if proband's mom for DMD has 2 consistent high CK's, she has a carrier risk of ____

Back 562

close to 100%

Front 563

normal CK's can reduce a proband's mom for DMD by ___ but only if mom's risk is ambiguous

Back 563

1/2

Front 564

BMD clinically overlaps with ____

Back 564

other limb-girdle dystrophies

Front 565

mutation in achondroplasia

Back 565

FGFR3

Front 566

achondroplasia is a ____ of function mutation

Back 566

gain

Front 567

Knockout mice for FGFR3 show ___ (phenotype)

Back 567

gigantism

Front 568

FGFR1/2 mutations cause ___ and are ___ of function mutations

Back 568

craniosynostoses, GOF

Front 569

FGFR1,2,and 3 mutations all show CpG ____as a mechanism of mutation

Back 569

deamination

Front 570

mutation in the PAX2 gene cause _____ and is a ____ of function mutation

Back 570

Waardenburg, loss of function

Front 571

waardenburg is a ____ disorder

Back 571

haploinsufficiency

Front 572

cirrhosis of liver, fatigue, endocrine failure, diabetes, loss of libido and impotence, leads to liver disease and malignancy if not treated, heart disease, AR inheritance

Back 572

hemochromatosis

Front 573

gen pop carrier risk of hemochromatosis?

Back 573

1:8-1:10

Front 574

hemochromatosis is associated with HLA-___ allele

Back 574

A3

Front 575

HLA-H gene is expressed in highest amounts in the ___ and ___ and is associated with transferring receptor in ____ gene

Back 575

gut and liver, C282Y

Front 576

motor neuron disease, anterior horn cells, muscular atrophy, most AR, many types

Back 576

SMA

Front 577

carrier frequency for SMA in Caucasians

Back 577

1:50

Front 578

most common fatal disorder of infancy and second most common childhood neuromuscular disease after DMD

Back 578

SMA

Front 579

SMA type I phenotype

Back 579

Werdnig-Hoffman, neonatal death

Front 580

SMA type II phenotype

Back 580

intermediate, onset in early childhood,early impairment in walking

Front 581

SMA type III

Back 581

Kugelberg-Welander, onset in late childhood, variable

Front 582

The SMA types are numbered due to ____

Back 582

the severity (1 most severe and more than that less severe)

Front 583

a phenotype of SMA requires homozygous deletions of exons 7 and/or 8 in ____ and is modified by ___ gene (having more will decrease severity)

Back 583

SMN1, SMN2

Front 584

carrier frequency of SMA

Back 584

1:40-1:60

Front 585

HD, bulbospinal muscular atrophy, spinocerebellar ataxias are all examples of ____ syndromes

Back 585

polyglutamine toxicity

Front 586

Expansions of polyglutamine toxicity syndromes usually occur through ___ germline

Back 586

paternal

Front 587

congenital myotonia or in later age with low set ears, myotonia, distal wasting, endocrine issues, personality differences; expands through mom

Back 587

myotonic dystrophy

Front 588

Fragile X is a ___ of function condition

Back 588

loss

Front 589

most common mutation in GJB2 gene in whites

Back 589

35delG

Front 590

disease mechanism in GJB2 mutations

Back 590

loss of gap junction prevents recycling of toxic ions and metabolites away from hair cells leading to their death

Front 591

protein controlling stability of nuclear envelope and maintenance of transcriptional programs

Back 591

lamin A/C disorders

Front 592

3 dominant lamin A/C disorders

Back 592

Emery-Dreifus muscular dystrophy and lipodystrophy, peripheral neuropathy

Front 593

recessive disorder of lamin A/C

Back 593

Hutchinson-Gilford Progeria Syndrome

Front 594

growth failure, loss of body fat and hair, aged-looking skin, stiffness of joints, hip dislocation, generalized atherosclerosis, heart disease and stroke, death by 13yo, weight <<<height, head large for face, prominent scalp veins, delayed and crowded teeth, delayed fontanelle closure, pear shaped thorax, small chin, thin limbs, tight joints, wide based shuffling gait, sclerodermatour skin changes over lower abdomen and thighs, LMNA mutation, AD

Back 594

Hutchinson-Gilford Progeria

Front 595

progressive weakness/wasting, cardiac conduction defect, need pacemaker by 20yo

Back 595

Emery-Dreifuss muscular dystrophy

Front 596

condition with Conotruncal heart defects, typical face (prominent full nasal tip, short philtrum, small inverted v-shaped mouth, abnormal ears, cleft palate), velopalatine dysfunction, increased incidence of hypocalcemia/thymic hypoagenesis, increased frequency MR and schizophrenia, AD inheritance

Back 596

22q11.2

Front 597

imperforate-stenotic anus, triphalangeal/hypoplasia/broad/polydactylous thumb, ear abnormalities, HL, increased incidence of cardiac anomalies, renal defects; variable penetrance, SALL1 gene, AD inheritance

Back 597

townes-brocks

Front 598

condition with supravalvular aortic stenosis, hypocalcemia, lateral supraorbital edema, blue sclera, stellate irides, epicanthal folds, high-set nose with flat bridge, large everted lower lip, small teeth, short stature, mild/mod MR, hyperacoustis, coarse voice, extrovert personality, occasional savant skills, AD microdeletion in elastin gene

Back 598

Williams Syndrome

Front 599

broad thumbs/halluces (possibly deviated), downslanted eyes, high nasal bridge, beak nose, high narrow palate, hypertrichosis, short stature, moderate MR, heart defects, keloids, happy personality, sleep apnea, strabismus, ptosis, tumors (meningioma, pilomatrixoma, leukemia), cryptorchidism, growth delay, behavior problems, almost all sporadic, AD inheritance, mutation in CREBBP gene

Back 599

rubinstein-taybi syndrome

Front 600

Primary craniofacial disorder with mild/severe malar hypoplasia, lower eyelid colobomas, high nasal bridge, micrognathia, high arched narrow palate, diagonal preauricular hair tufts of lateral forehead/face, microtia with mixed deafness, CP, normal mentation, AD inheritance, mutation in TCOF1 gene, normal IQ

Back 600

treacher collins

Front 601

gene mutation causing Townes-Brocks gene

Back 601

SALL1

Front 602

gene mutation causing Williams syndrome

Back 602

ELN

Front 603

gene mutation causing Rubinstein-Taybi syndrome

Back 603

CREBBP

Front 604

gene mutation causing Treacher Collins

Back 604

TCOF1

Front 605

pre-/postnatal growth retardation with MR, frequent microcephaly, synophrys, eyebrow-lash hypertrichosis, high-set nose, thin upper lip, downturned mouth corners, coarse voice, body hypertrichosis, variable limb deficiencies, heart defects, reflux, diaphragmatic hernias, cutis marmorata, mutation in NIPBL gene

Back 605

Cornelia de Lange Syndrome

Front 606

mutation in cornelia de lange

Back 606

NIPBL

Front 607

mutation in COL2A1, achondrogenesis II, SED congenital, Kniest dysplasia, hypochondrogenesis, more severe and non-ocular form, myopia with retinal detachment, flat midface, CP with Pierre Robin features, cataracts, sensorineural deafness, epiphyseal dysplasia, arthritis

Back 607

stickler syndrome

Front 608

mutation in DHCR7 gene, MR, microcephaly, hypotonia, postnatal growth retardation, 2-3 toe syndactyly, hypospadias in males, polydactyly, low-set ears, ptosis, holoprosencephaly, cholesterol problem, repeated self-injury and violent outbursts/tantrums, hyperactivity, malformations of heart/lungs/kidneys/GI tract/genitalia,

Back 608

smith-lemli-opitz

Front 609

mutation in stickler syndrome

Back 609

COL2A1

Front 610

mutation in smith-lemli opitz

Back 610

DHCR7

Front 611

defect of peroxisomal biogenesis, increased VLCFA, severe neonatal hypotonia, MR, early demise, large anterior fontanel, increased lateral and anterior neck fat, narrow palpebral fissures, prominent upslanted eyes, cataracts, club feet, stippled epiphyses

Back 611

Zellweger syndrome

Front 612

proportionate pre-/postnatal growth deficiency with low to normal head circumference, triangular face, thin upper lip with downturned mouth corners, clinodactyly, asymmetry of limbs, infancy excessive sweating, IQ normal, increased risk of urogenital anomalies

Back 612

Russell-Silver syndrome

Front 613

mutation in NSD1 gene, prenatal/postnatal overgrowth with macrocephaly, mild-mod MR, poor coordination, large triangular face, downslanted eyes, open mouth, large hands/feet, increased risk of malignancy (Wilms, sacral teratoma), similar to Weaver syndrome

Back 613

Sotos syndrome

Front 614

chromosome involved in Russell-Silver

Back 614

7

Front 615

gene mutation in Sotos

Back 615

NSD1

Front 616

EDA1 mutation, anhidrosis, hypohidrosis, hypotrichosis of scalp/eyebrows/eyelashes, conical teeth (hypodontia), oligodontia, flat nasal bridge, rosy red lips, periorbital hyperpigmentation, reduced sweat pores, at birth peeling skin and perioral hyperpigmentation

Back 616

X-linked hypohidrotic ectodermal dysplasia

Front 617

GNAS mutations (imprinted too), maternal transmission leads to this condition with hypocalcemia, increased PTH and PO4, obesity, MR, decreased HT, brachydactyly, SC calcifications

Back 617

pseudohypoparathyroidism

Front 618

GNAS mutations (imprinted too), paternal transmission leads to this condition with

Back 618

pseudo-/pseudohypoparathyroidism

Front 619

mutation in MLL2, Long palpebral fissures, arched eyebrows, lower eyelid eversion, flat nasal bridge, short nasal septum, prominent abnormal ears, large fingertip pads, short 5th fingers, MR, microcephaly, mixed growth problems, FTT, reflux, heart defects, long eyelashes, hypoglycemia, hypotonia, lagophthalmos, immune problems, late obesity

Back 619

Kabuke syndrome

Front 620

mutation in X-linked hypohidrotic ectodermal dysplasia

Back 620

EDA1

Front 621

mutation/imprinting in Albright Hereditary Osteodystrophy

Back 621

GNAS

Front 622

mutation in PAX3 gene leading to marked hypopigmentation and limb deficiency, white forelock, heterochromia irides, deafness, hypertelorism, dystopia canthorum, thick medial eyebrows, flat nasal bridge, prominent nasal tip with age

Back 622

Waardenburg Syndrome, type I (AD)

Front 623

Another type of Waardenburg syndrome but lacking dystopia canthorum

Back 623

type II WS

Front 624

another type of Waardenburg syndrome but associated with HIrschsprung disease, pigmentary abnormalities, SN deafness, neurological problems

Back 624

Waardenburg-Shah

Front 625

genes involved in type II/IV Waardenburg

Back 625

SOX10, EDNBR, EDN3

Front 626

mutation involved in type I Waardenburg syndrome

Back 626

PAX3

Front 627

scarcity of bile ducts (cholestasis), heart defects (PS, PPS), vertebral anomalies with characteristic facial features (deep-set eyes, posterior embryotoxin, high triangular shaped nasal bridge, full nasal tip, mild MR may occur, JAGGED1 gene mutation, DD, growth failure, butterfly vertebra

Back 627

Alagille

Front 628

gene mutations in Alagille Syndrome

Back 628

JAG1 or NOTCH2

Front 629

condition lethal in males, seizures, severe MR, agenesis corpus callosum, little/no speech, retinal lacunae (choroid showing through), vertebral defects, rib anomalies, polydactyly, face normal

Back 629

Aicardi Syndrome

Front 630

only type I (XLD) and others mostly AR inheritance, mixed polydactyly and tongue hamartomas, MR, clefting, hypertelorism, agenesis corpus callosum, Dandy-walker cyst

Back 630

oral-facial digital syndromes

Front 631

aortica dilatation/dissection, tall/thin, arachnodactyly, pectus, large wing span, triangular face, malar hypoplasia, high narrow palate, myopia, ectopic/unstable lens, scoliosis, dural ectasia, hernias, striae, pneumothoraces, 4,5 finger contractures, neonatal form is lethal

Back 631

marfan syndrome

Front 632

gene mutation in marfan syndrome

Back 632

FBN1

Front 633

CP, hypertelorism, conductive deafness, mild MR, tree frog digits with short and broad thumbs/hallices, bowed limbs, type II tibiae/fibulae, omphalocele, filamin A defect

Back 633

oto-palato-digital syndrome

Front 634

gene mutation in oto-palatal-digital syndrome

Back 634

filamin A defect

Front 635

high risk of basal cell carcinoma, increased risk of medulloblastoma and ovarian tumors, macrocephaly, high prominent forehead, hypertelorism, flat nasal bridge, jaw cysts, calcified falx, palm pits, polydactyly, pectus, bifid ribs, CL/P, PTCH gene defect

Back 635

Gorlin syndrome

Front 636

gene defect in Gorlin syndrome

Back 636

PTCH

Front 637

pulmonary stenosis, low frequency of HCM, high nasal bridge, downslanting eyes/ptosis, light color irides, malar flatness, thick low-set ears, curly hair, short stature, web neck, pectus excavatum, cryptorchidism, mild MR in 50%, PTPN11 gene mutation

Back 637

Noonan syndrome

Front 638

gene defect in Noonan Syndrome

Back 638

PTPN11

Front 639

macrocephaly, frontal bossing, hypertelorism, polydactyly (broad thumbs/hallices), agenesis CC, syndactyly, pre- and postaxial polydactyly, hypothalamic hamartomas, postaxial polydactyly, caused by GLI3 mutation

Back 639

Greig Cephalopolysyndactyly

Front 640

gene in Greig Cephalopolysyndactyly

Back 640

GLI3

Front 641

mutation in P63 gene, absence of one or more central digits of hand or foot ("lobster claw hand"), syndactyly,, ectodermal dysplasia (dry/scale-like skin, absent sweat glands, etc), CP clefting, vesicoureteral reflux, recurrent UTI's, decreased pigment of hair and skin, missing/abnormal teeth, enamel hypoplasia, absent punctae in lower eyelids, photophobia, cognitive impairment and kidney anomalies and conductive HL

Back 641

ectrodactyly-ectodermal-clefting (also known as split hand-foot syndrome)

Front 642

gene mutation in split hand foot syndrome

Back 642

P63

Front 643

coarctation of aorta seen in primarily what condition?

Back 643

Turner Syndrome

Front 644

supravalvular aortic stenosis seen in primarily what condition?

Back 644

Williams Syndrome

Front 645

which condition includes ASD or VSD and cardiac conduction issues?

Back 645

Holt-Oram syndrome

Front 646

which condition includes VSD, ASD, and tetrology of Fallot and less commonly truncus arteriosus, transposition of the great arteries?

Back 646

VACTERL

Front 647

___% of Sudden Cardiac death have underlying CAD including congenital coronary anomalies but not inherited arrhythmias

Back 647

70-90%

Front 648

risk factors for CAD

Back 648

smoking, HTN, DM, elevated LDL, fam Hx of heart disease, sedentary lifestyle, previous MI, heart failure from other causes, arrhythmia of unknown cause, episodes of fainting of unknown cause, low ejection fraction (EF)

Front 649

pitfalls of polar body biopsy

Back 649

failure of amplification, crossing over, technically difficult

Front 650

risk of abnormal phenotype in a balanced Robertsonian translocation is ___% above background risk of 3%

Back 650

less than 1%

Front 651

risk of abnormal phenotype in a balanced reciprocal translocation is __%

Back 651

6%

Front 652

Consider ___ testing in a balanced Robertsonian translocation carrier with an abnormal phenotype

Back 652

UPD

Front 653

consider ___ testing in a balanced reciprocal translocation carrier with an abnormal phenotype

Back 653

microarray

Front 654

largest risk of abnormal phenotype in ___ carriers with de novo balanced rearrangements

Back 654

inversion (then reciprocal translocations then robersonian translocations)

Front 655

which condition is seen in mosaic nature only with mostly normal phenotype; mosaicism seen in bladder, kidney, and intestine cells

Back 655

trisomy 20

Front 656

IUGR and preeclampsia seen in ____ mosaicism

Back 656

trisomy 16

Front 657

HCM is an inherited disease of ____

Back 657

sarcomeres

Front 658

hallmark feature of HCM is ___

Back 658

thickening of wall of heart muscle (L ventricular hypertrophy)

Front 659

If the walls get too thick in HCM, it can cause _____

Back 659

block flow of blood out of heart (outflow obstruction

Front 660

2/3 of HCM cases have ___ wall thickening

Back 660

asymmetric

Front 661

Most people with HCM have onset between ___ years old

Back 661

15-35

Front 662

clinical presentation of HCM

Back 662

fainting/passing out, exercise intolerance, fatigue, orthostatic hypotension, arrhythmias, SCD (10-20%)

Front 663

DX tests for HCM

Back 663

ECHO and/or cardiac MRI showing LVH and ECG with prominent Q waves in inferior/lateral leads and T-wave inversions

Front 664

___% of HCM is genetic and ___% is not

Back 664

60-70%, 30-40%

Front 665

MYH7, MYBCP3, TNNT2, MYL2, MYL3, ACTC, TNNI3, TPM1, TNNC1, and TTN are all genes involved in what condition?

Back 665

HCM

Front 666

gene most associated with genetic HCM?

Back 666

MYH7 (40%) followed by MYBCP3 (30%)

Front 667

heart failure, HCM, cardiac transplantation, unexplained sudden death, unexplained cardiac conduction system disease and/or arrhythmia, unexplained stroke or other thromboembolic disease are all indicators of ___ in the family,

Back 667

HCM

Front 668

gene associated with HCM with Wolf Parkinson White

Back 668

PRKAG2

Front 669

inheritance of HCM with WPW

Back 669

AD

Front 670

skeletal myopathy and opthalmologic manifestations including retinal distrophy, mutation in LAMP2 gene, X-linked

Back 670

Dannon syndrome

Front 671

gene involved in Dannon Syndrome

Back 671

LAMP2

Front 672

gene involved in Fabry disease

Back 672

GLA

Front 673

inheritance of Fabry disease

Back 673

X-linked

Front 674

MT-TK, MT-TG, MT-TI, MT-TQ are all mitochondrial genes involved in ___ condition

Back 674

HCM

Front 675

in a family with MYH7 gene mutation, HCM would be expected to appear around what age in life?

Back 675

2nd decade

Front 676

Which mutation in the MYH7 gene increases risk of SCD?

Back 676

R403Q

Front 677

What onset and phenotype is expected for someone with a MYBPC3 mutation?

Back 677

4th/5th decade onset, more severe prognosis with higher risk of SCD

Front 678

what phenotype is expected for someone with a TNNT2 mutation?

Back 678

mild LVH and increased risk of SCD in families

Front 679

medical management for HCM

Back 679

beta blockers, calcium channel blockers, antiarrhythmics, catheter based ablation, surgical myectomy, pacemaker placement, ICD placement, 12-18yo ECG and echo annually and >18-21 echo and ECG every 3-5 yrs

Front 680

in someone with an HCM mutation, avoid what activities?

Back 680

competitive endurance training, burst activities, dehydration, hypovolemia (severe blood loss), certain meds

Front 681

Left ventricle enlargement and systolic dysfunction leading to edema, orthopnea, paroxysmal dyspnea, fatigue, dyspnea on exertion, arrhythmias, thromboembolic disease seen in what condition?

Back 681

Dilated Cardiomyopathy (DCM)

Front 682

Penetrance of DCM

Back 682

40-80%

Front 683

age of onset average for DCM

Back 683

40yo

Front 684

acquired causes of DCM

Back 684

ischemic injury resulting from MI or CAD, valvular and congenital heart disease, toxins like anthryacyclines, thyroid disease, inflammatory conditions, myocarditis, severe long-standing HTN, radiation, iron overload (hemochromatosis)

Front 685

DCM is inherited in ___% of people

Back 685

20-50%

Front 686

inheritance for 80-90% of DCM cases that are genetic

Back 686

AD

Front 687

X-linked causes of DCM (4)

Back 687

DMD, BMD, Emery-Dreifuss MD, Barth Syndrome

Front 688

AR cause of DCM (1)

Back 688

Alstrom syndrome

Front 689

mitochondrial causes of DCM (3)

Back 689

MERF, MELAS, isolated DCM

Front 690

75% of DCM caused by ___ genes and small amount from ACTC1, DES, LMNA, MYH7, TNNT1, AXN5A, PSEN1, and PSEN2

Back 690

unknown

Front 691

medical management of DCM

Back 691

restriction of alcohol, salt/fluid intake, daily endurance exercise for 30 mins, ICD, pacemaker, ACE inhibitors/beta blockers/diuretics/digoxin, cardiac transplant, ecg and ECHo every 1-2 or 3 yrs depending on situation

Front 692

inherited disorder affecting dilation of R or L ventricle of heart, dilation of R ventricle causing poor contractions of heart, fatty infiltration of either ventricle, loss of muscle leading to thinning of ventricle walls, heart palpitations, ventricular tachycardia, ventricular fibrillation, syncope, chest pain, SOB, intolerance to exercise, heart failure

Back 692

arrythmogenic R ventricular Dysplasia/CM

Front 693

which gender is more frequently affected with arrythmogenic R ventricular dysplasia/CM

Back 693

males

Front 694

average age of onset of arrythmogenic R ventricular dysplasia/CM

Back 694

31yo

Front 695

arrythmogenic R ventricular dysplasia/CM seen more commonly in what populations? (2)

Back 695

Italy and Greece

Front 696

Dx criteria for arrythmogenic R ventricular dysplasia/CM

Back 696

ECG, exercise stress test, MRI, Bx

Front 697

DSP, PKP2, DSG2, TMEM43, JUP, RYR2 all associated genes with what condition?

Back 697

arrythmogenic R ventricular dysplasia/CM

Front 698

inheritance of arrythmogenic R ventricular dysplasia/CM

Back 698

AD

Front 699

penetrance of arrythmogenic R ventricular dysplasia/CM in mutation carriers?

Back 699

50-80%

Front 700

__% of arrythmogenic R ventricular dysplasia/CM is inherited?

Back 700

30-50%

Front 701

medical management for arrythmogenic R ventricular dysplasia/CM

Back 701

beta blockers, ICD, surgical ablation, heart transplant, avoid vigorous athletic activity and stimulants, ECHO, ECG, MRI, and electrophysiology studies annually from 12yo

Front 702

condition that is a form of arrythmogenic R ventricular dysplasia/CM and includes wooly hair, palmo-plantar keratoderma (blisters on hands and feet), mutations in JUP gene, and AR inheritance

Back 702

Naxos disease

Front 703

Naxos disease gene

Back 703

JUP

Front 704

result of abnormal heart development at 5-8 weeks gestation where spongy material making up myocardium does not compact and diseappear leaving behind trabeculations; leads to thromboembolic events, a fib, ventricular tachycardia, heart failure

Back 704

non-compaction CM

Front 705

__% of left ventricular non-compaction is inherited

Back 705

70%

Front 706

adult onset of left ventricular non-compaction has an average onset of ___yo whereas the congenital form onset is ___yo

Back 706

40, 6

Front 707

inheritance of left-ventricular non-compaction

Back 707

AD

Front 708

penetrance of left-ventricular non-compaction

Back 708

50-100%

Front 709

gene associated with left-ventricular non-compaction, DCM, X-linked infantile CM, and Barth Syndrome

Back 709

TAZ

Front 710

LDB3, LMNA, MYH7, MYBPC3, TNNT2, ACTC, and TAZ are all genes associated with what condition?

Back 710

left-ventricular non-compaction

Front 711

medical management of left-ventricular non-compaction

Back 711

no guidelines, ICD, oral anticoagulants, heart transplant, beta blockers, calcium channel blockers

Front 712

disorder of heart muscle in which walls of ventricles become stiff but not thickened so resist normal filling with blood. leads to SOB at first with exercise and later with rest, fatigue, inability to exercise, edema, weight gain, nausea/bloating/poor appetite, palpitations

Back 712

restrictive CM

Front 713

least common cardiomyopathy

Back 713

restrictive CM

Front 714

CM with highest SCD risk

Back 714

restrictive CM

Front 715

metabolic disorders associated with restrictive cardiomyopathy?

Back 715

Gaucher, MPS, Fabry, carcinoid syndrome

Front 716

causes of restrictive CM besides genetic

Back 716

endomyocardial fibrosis, previous XRT therapy, infiltrative disorders like amyloidosis/sarcoidosis/hemachromatosis

Front 717

penetrance of restrictive CM with mutation

Back 717

40%

Front 718

MYH7, TNNI3*, ACTC1, TNNT2, and DES are all genes associated with what condition?

Back 718

restrictive CM

Front 719

inheritance of restrictive CM

Back 719

AD

Front 720

heritable electrical disorder in heart, irregular heart beat, prolonged T-wave, variable severeity, onset in childhood and adolescence, causes syncope, tachycardia, v fib, seizures, cardiac arrest; deafness in certain forms

Back 720

Long QT syndrome

Front 721

greater risk in Long QT syndrome in which gender?

Back 721

women

Front 722

factors affecting baseline QT interval

Back 722

genetics, age and gender, CNS disorders, electrolyte alterations, certain meds

Front 723

condition with mutation in KCNQ1,KCNH2,SCN5, KCNE2 genes (LQT1,2,3,5,6)

Back 723

Romano-Ward Syndrome

Front 724

condition with mutations in homozygous LQT1 or 2 in KCNQ1, KCNH2

Back 724

Jervell-Lange-Nielsen Syndrome

Front 725

condition with mutation in LQT7 gene

Back 725

Andersen-Tawil Syndrome

Front 726

condition with mutation in LQT8 gene

Back 726

Timothy Syndrome

Front 727

penetrance of Long QT syndrome?

Back 727

~70%

Front 728

inheritance of Long QT syndrome

Back 728

AD and AR

Front 729

there are ____ subtypes of Long QT syndrome

Back 729

13

Front 730

medical management for long QT syndrome

Back 730

beta blockers, electrical cardioversion, external defib, ICD, ECG and eval by electrophysiologist

Front 731

Which subtypes of long QT syndrome benefit most from beta blockers

Back 731

1 and 2

Front 732

pacemakers most useful in patients with what subtype of long QT syndrome?

Back 732

3

Front 733

heritable disorder of electrical system of heart, short QT on EKG and tall, peaked T waves, increased risk for SCD and a fib

Back 733

Short QT syndrome

Front 734

inheritance of short QT syndrome

Back 734

AD

Front 735

KCNH2, KCNQ1, and KCNJ2 gene are associated with what condition?

Back 735

short QT syndrome

Front 736

abnormal ECG pattern and increased risk for syncope and SCD (responsible for 4-12% of all SCD and up to 50% of sudden deaths with strucurally normal hearts); ST elevation on ECG and broadened QRS, mean age of death 40yo but may present as SIDS, SCN5A mutation

Back 736

Brugada syndrome

Front 737

medical management of Brugada Syndrome

Back 737

no ICD in asymptomatic patients, antiarrhythmic meds may be helpful, beta blockers COUNTERindicated; avoid high fever, anesthetics, antidepressants, antipsychotics

Front 738

SCN5A*, GPD1L, SCN1B, CACNA1C, CACNB2, SCN3B, KCNE3 genes are associated with what condition?

Back 738

Brugada syndrome

Front 739

inheritance of Brugada Syndrome

Back 739

AD

Front 740

episodic syncope during exercise or acute emotion, family history of SCD <40yo, may be associated with SIDS, mean age of onset 7-9yo; causes exercise induced polymorphic ventricular arrhythmia, bidirectional VT, irregular polymorphic VT without stable QRS vector, resting ECG normal, history of exercise or emotion-related palpitations and dizziness, absence of structural cardiac abnormalities

Back 740

catecholaminergic polymorphic ventricular tachycardia (CPVT)

Front 741

gene most associated with catecholaminergic polymorphic ventricular tachycardia

Back 741

RYR2 gene

Front 742

penetrance of RYR2 gene in catecholaminergic polymorphic ventricular tachycardia

Back 742

83%

Front 743

CASQ2 is the gene associated with ___ inheritance in catecholaminergic polymorphic ventricular tachycardia

Back 743

AR

Front 744

medical management for catecholaminergic polymorphic ventricular tachycardia

Back 744

beta blockers, ICD; monitor with ECG, holter monitor, exercise stress test

Front 745

drastic increase in pressure in pulmonary artery, increase in pressure causes right side of heart to work harder to pump blood causing right side of heart to become much more muscular causing heart failure; causes SOB, fatigue, syncope, chest pain, palpitations, leg edema, Reynaud's phenomenon

Back 745

pulmonary artery hypertension

Front 746

___ pulmonary hypertension is the type due to underlying medical cause

Back 746

secondary

Front 747

pulmonary hypertension is twice as common in which gender?

Back 747

females

Front 748

causes of pulmonary hypertension besides genetics

Back 748

lung disorders, loss of long tissue, chronic liver disease, obesity, drugs/toxins, low O2 levels, heart failure, HIV, genetics

Front 749

60-70% of people with hereditary pulmonary artery hypertension have mutations in what gene?

Back 749

BMPR2

Front 750

penetrance of pulmonary artery htn with hereditary form?

Back 750

20%

Front 751

medical management for pulmonary artery hypertension

Back 751

ECG, X-ray, ECHO, avoid heavy and strenuous exercise, discuss all medication use with MD, caution when considering pregnancy, vasodilators, endothelin receptor blockers, diuretics, anticoagulants, oxygen, lung transplant

Front 752

an inherited condition characterized by slowly pregressive peripheral sensorimotor neuropathy and autonomic neuropathy, CM, vitreous opacities, CNS amyloidosis, onset 3-7th decades

Back 752

TTR-associated amyloidosis

Front 753

deposit of abnormal amyloid in heart tissue which may affect electrical signals

Back 753

cardiac amyloidosis

Front 754

protein deposit exhibiting beta sheet structure

Back 754

amyloid

Front 755

disease with buildup of amyloid in body tissue and organs

Back 755

amyloidosis

Front 756

3 types of TTR amyloidosis

Back 756

TTR amyloid neuropathy, cardiac amyloidosis, leptomeningeal/CNS amyloidosis

Front 757

gene involved in amyloidosis

Back 757

transthyretin gene

Front 758

transthyretin transports __ and ___ throughout the body

Back 758

retinol and thyroxine

Front 759

De novo rate of TTR-amyloidosis

Back 759

66%

Front 760

2 common mutations seen in amyloidosis

Back 760

V30M (Portuguese, Swedish, and Japanese) and V122I (Af. American population)

Front 761

treatment for amyloidosis

Back 761

salt and/or fluid restrictions, diuretics, pacemaker, heart transplant, liver transplant

Front 762

same or similar phenotype due to mutation in single genes (ex: achondroplasia, thanatophoric dysplasia)

Back 762

single gene syndrome families

Front 763

same or similar phenotype due to mutation in different genes (ex: FA, Bardet-Biedl)

Back 763

multiple gene syndrome families

Front 764

Multiple gene families are ___ common than single gene families

Back 764

less

Front 765

Noonan and RAF1 disorders are both ___ of function mutations, but Leopard and SHOC 2 are ___ of function mutation

Back 765

gain, loss

Front 766

PTPN11 gene associated with Noonan has also been found mutated in patients with ___ syndrome

Back 766

multiple lentigenes (Leopard)

Front 767

Some PTPN11 negative Leopard syndrome patients have ___ mutations, not the common 12q24.1 mutation

Back 767

RAF 1

Front 768

multiple lentigenes, electrocardiographic conduction defects, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth, deafness (sensorineural), hypertrophic CM

Back 768

leopard syndrome

Front 769

gene mutation causing 13% of Noonan cases, Noonan-like facies, stature/IQ normal, pulmonary stenosis more common, ectodermal defects common, mutation is GOF

Back 769

SOS1

Front 770

gene mutation causing 5-10% of Noonan syndrome, 80-95% have HCM, less consistent Noonan facies, can cause Noonan and Leopard syndrome, GOF mutation

Back 770

RAF1

Front 771

gene mutation causing 25% of Noonan where PTPN11 is neg, LOF mutation, Noonan-like face and short stature, web neck, pectus, heart defects, DD, high wide forehead hypertelorism, ptosis, downslanted eyes, low-set posteriorly rotated ears, macrocephaly, loose Anagen hair resulting in sparse hair, increased skin pigmentation, mitral valve dysplasia w/ or w/out PS, HCM or septal defects

Back 771

SHOC2

Front 772

BRAF, KRAS, MEK1, MEK2 are all associated with ___ syndrome and are ___ of function mutations

Back 772

cardio-facio-cutaneous syndrome, gain

Front 773

HRAS is a gene association with which syndrome?

Back 773

Costello

Front 774

curly sparse scalp hair, sparse eyebrows/lashes, relative macrocephaly, poor growth, DD, ectodermal problems like dry skin/icthyosis/eczema, hyperkeratosis, nevi, Noonan-like facies with full nose, PS, HCM, septal defects; 4 genes associated with this in the MAPK pathway

Back 774

cardio-facio-cutaneous syndrome

Front 775

tumor predisposition for rhabdomyosarcoma, neuroblastoma and bladder cancer; postnatal growth deficiency preceded by LGA, short stature, diffuse hypotonia and joint laxity, ulnar deviation of wrist/fingers, MR< relative macrocephaly, coarse face with large lips/curly hair/flat nasal bridge/nasal papillomata/macroglossia, skin thick but soft hands and feet have deep palm and sole creases, hypertrophy and congenital heart defects

Back 775

costello syndrome

Front 776

which form of FA is X-linked recessive and causes a vacteral/hydrocephalus phenotype?

Back 776

FANC B

Front 777

short stature, macrocephaly, rounded prominent forehead, thumb/radial hypoplasia, skin pigmentary abnormalities, eye abnormalities, 3-5% have duodenal atresia, imperforate anus, TE fistula/esophageal atresia, pancytopenia w/ onset 3-7yo with progressive BM failure, significant increased risk of neoplasia including leukemias (carriers increased risk of this too), increased spontaneous chromosome breakage, abnormal pigmentation, radial, GU, ear, heart GI or CNS malformation, HL, hypogonadism, DD, solid tumors of head/neck/esophagus/cervix/vulva/liver

Back 777

Fanconi anemia

Front 778

defects in multiple genes, ciliary dysfunction, obesity, polydactyly, RP, hypogenitalism (males), renal abnormalities, MR, cognitive impairment, complex female GU malformations, night blindness by 7-8yo and legally blind by 15.5yo, LD, AR inheritance

Back 778

Bardet-Biedl Syndrome

Front 779

genes associated with Bardet-Biedl

Back 779

BBS1-13

Front 780

choanal atresia, severe proptosis, hypertelorism, beak nose, malar-maxillary hypoplasia, mitten syndactyly of hands and feet, AD inheritance

Back 780

Apert

Front 781

gene associated with Apert and Crouzon

Back 781

FGFR2

Front 782

proptosis, hypertelorism, beak nose, malar-maxillary hypoplasia, no non-craniofacial features, AD inheritance

Back 782

Crouzon

Front 783

3 types: FGFR1 is milder and causes osteoglophonic dwarfism and AD Kallman syndrome; FGFR2 mutation is more severe with MR and Kleeblattschadel (cloverleaf skull)

Back 783

Pfeiffer syndrome

Front 784

mutation in Saethre-Chotzen

Back 784

TWIST1

Front 785

similar to achondroplasia but more mild with short stature, stocky build, rhizo- or mesomelia, limited elbow extension, brachydactyly, mild joint laxity, macrocephaly, sciolosis, genu varum, lumbar lordosis, mild-mod MR, LD, adult onset osteoarthritis, FGFR3 mutation

Back 785

hypochondroplasia

Front 786

lethal condition, more severe x-ray features than achondroplasia, type II associated with cloverleaf skull (kleeblattschadel)

Back 786

thanatophoric dysplasia

Front 787

achondroplasia, hypochondroplasia, and thanatophoric dysplasia are all due to mutations in what gene?

Back 787

FGFR3

Front 788

hitchhiker thumbs, cystic ears, bowed limbs, club feet, clinodactyly, knee contractures, spondylometaphyseal dysplasia with short first metacarpals and irregularly contoured proximal phalanges, small chest, large joint contractures, cleft palate, cystic ear swelling, ulnar deviation of fingers, clubfoot, low tone, normal IQ, mutation in SLC26A2

Back 788

diastrophic dysplasia

Front 789

mutation in which gene leads to diastrophic dysplasia, achondrogenesis 1B, atelosteogenesis type 2, and AR MED

Back 789

SLC26A2

Front 790

mesomelia with Madelung deformity, isolated short stature, mutation on X-chromosome and can cause either haploinsufficiency or homozygous mutations

Back 790

Dyschondrosteosis/Langer Mesomelia; Leri-Will with haploinsufficiency of SHOX and Langer Mesomelia if homozygous mutations

Front 791

gene associated with dyschondrosteosis and Langer Mesomelia

Back 791

SHOX

Front 792

Greig Cephalosyndactyly and Pallister-Hall syndrome are both caused by mutations in this gene

Back 792

GLI3

Front 793

hypothalamic hamartomas and postaxial polydactyly, nail dysplasia, imperforate anus, tracheal/laryngeal defects, GLI3 mutation, can be neonate lethal, pituitary insufficiency, renal abnormalities

Back 793

Pallister-Hall syndrome

Front 794

Mutation in which gene can cause Hutchinson-Gilford, mandibuloacral dysplasia, restrictive dermopathy CMT 2B, AR Emery-Dreifuss MD

Back 794

lamin A/C

Front 795

gene mutation causing popliteal pterygium/lip pit syndrome?

Back 795

IRF6

Front 796

gene mutation leading to EEC, Hay-Wells, Rapp-Hodgkin, limb mammary syndrome, adult syndactyly, and split hand/foot typ 4 syndrome

Back 796

P63

Front 797

CL and or CP, conical teeth, hypodontia to anodontia, ankylblepharon, skin hyperpigmentation, absent or dystrophic nails, sparse to absent scalp hair, AD inheritance, mutation in P63 gene, congenital adhesions of the eyelids, ectodermal dysplasia, chronic inflammatory dermatitis of scalp

Back 797

Hay-Wells Ectodermal dysplasia

Front 798

gene mutation causing Melnick-Needles, frontometaphyseal dysplasia, XL pericentricular nodular heterotopias, and oto-palato-digital syndrome

Back 798

filamin A

Front 799

inheritance of oto-palato-digital syndrome

Back 799

XLD

Front 800

EDS types I and II are considered the ___ form and involve mutations in collagen type ____

Back 800

classic, 5A1 and 5A2

Front 801

EDS type III is the ___ form

Back 801

hypermobile

Front 802

EDS type IV is the __ form and involves mutations in collagen type ___

Back 802

vascular, 3A1

Front 803

EDS type VI is the ___ form of EDS

Back 803

kyphoscoliosis

Front 804

EDS type VII is the ____ type

Back 804

arthrochalasia

Front 805

which type of Stickler syndrome has more severe HL?

Back 805

2

Front 806

which type of stickler syndrome is the non-ocular form with COL11A1 and COL11A2 mutations?

Back 806

3

Front 807

which type of stickler syndrome has myopia with retinal detachment, flat midface, CP with Pierre Robin features, cataracts and SNHL, epiphyseal dysplasia, secondary arthritis and hip/spine problems?

Back 807

1

Front 808

___ mutations lead to Stickler and deafness

Back 808

COL11A1

Front 809

____ mutations lead to non-ocular Stickler, OSMED/AR W-Z, Weissenbacker-Zweymuller, and Marshall syndrome

Back 809

COL11A2

Front 810

Most frequent gene associated with Stickler Syndrome

Back 810

COL2A1

Front 811

Besides Marfan, ____ phenotype can also be caused by FBN1 mutations?

Back 811

MASS: mitral valve prolapse, aortic root diameter, skin stretch marks and skeletal features of Marfan

Front 812

congenital contractural arachnodactyly gene mutation?

Back 812

FBN2

Front 813

proptosis, craniosynostosis, CP, blue sclera, micrognathia and camptodactyly in type I; type 2 has milder facial features and prominent forehead, skin manifestations; both cause vessel tortuosity and aneurysms

Back 813

Loeys-Dietz

Front 814

gene mutations in Loeys-Dietz or rarely Marfan Syndrome

Back 814

TGFBR1 and 2

Front 815

gene mutation causing Renpenning syndrome, Sutherland-Haan, Golabi-Ito-Hall, Cerebropalatocardiac Syndrome, Porteous Syndrome and additional XLMR families

Back 815

PQBP1 gene (Xp11)

Front 816

gene causing XLMR (syndromic, non-syndromic), West syndrome (XL infantile spasms), XLAG (ambiguous genitalia, ACC, lissencephaly), XL lissencephaly, Partington syndrome (MR, hand dystonia)

Back 816

ARX (aristaless gene) on Xp22

Front 817

gene causing ATR-X syndrome, Juberg-Marsidi, Carpenter-Waziri, Holmes-Gang, Smith-Fineman-Myers, XLMR/spastic paraplegia, Chudley-Lowry syndromes

Back 817

ATR-X gene on Xq13.3

Front 818

mutation causing Xl hydrocephalus, MASA syndrome, XL agenesis CC, and CRASH syndrome (corpus, retardation, adducted thumbs, spastic paraplegia, hydrocephalus)

Back 818

L1CAM on Xq28

Front 819

2 genes causing congenital deafness in recessive form and progressive childhood deafness in dominant form which can include skin findings (palmarplantar keratoderma, KID syndrome)

Back 819

GJB2 (Cx26) and GJB6 (Cx30)

Front 820

keratitis, icthyosis, deafness

Back 820

KID syndrome

Front 821

DFNA inheritance is ____, DFNB is ____, DFN is ____

Back 821

AD, AR, X-linked

Front 822

oculocutaneous albanism, bleeding diathesis, hypopigmentation of skin and hair, nystagmus, reduced iris pigment, reduced retinal pigment, foveal hypoplasia, increased crossing of optic nerve fibers, can develop skin cancer/pulmonary fibrosis/colitis

Back 822

Hermansky-Pudlak syndrome

Front 823

HPS1, HPS3-8, AP3B1 genes are involved in what condition

Back 823

Hermansky-Pudlak syndrome

Front 824

bilateral severe SNHL, temporal bone abnormalities, vestibular abnormalities, goiter in 75% though only 10% have abnormal thyroid function

Back 824

Pendred syndrome

Front 825

SLC26A4 gene associated with what condition?

Back 825

Pendred syndrome

Front 826

inheritance of Pendred

Back 826

AR

Front 827

episodic abdominal pain, cramping and diarreah, occasional hematochezia (blood in stool), may involve any part of intestinal tract, transmural ulceration and granulomas of GI tract, fistulas, patchy involvement of terminal ileum and ascending colon, extraintestinal manifestations including inflammation of joints/eyes/skin

Back 827

Crohn disease

Front 828

NOD2/CARD15 is the gene increasing one's risk of what condition?

Back 828

Crohn Disease

Front 829

polyuria, polydipsia, polyphagia, hyperglycemia, ketosis, wasting

Back 829

IDDM

Front 830

IVS8+G>A mutation is common in what gene/condition?

Back 830

SLC26A4/Pendred

Front 831

95% of white patients with IDDM express a ___ or ___ allele or both

Back 831

DR3 or DR4

Front 832

hyperglycemia, relative insulin deficiency, insulin resistance, obesity, acanthosis nigricans

Back 832

NIDDM

Front 833

TCF7L2 and PPARG may be associated with an increased risk of ____

Back 833

NIDDM

Front 834

CBFA2/RUNX1 mutations may increase one's chance of ____

Back 834

AML

Front 835

QT prolongation and T-wave abnormalities, ventricular tachycardia causing syncope during exercise and high emotion; sometimes results in v fib, aborted cardiac arrest, sudden death, 1-2 syncopal episodes in pre-teens to 20's

Back 835

Romano-Ward Syndrome

Front 836

nosebleeds, mucocutaneous telangiectaseias, visceral AV malformation (pulmonary, cerebral, hepatic, spinal, GI)

Back 836

HHT

Front 837

ACVRL1 and ENG are mutations seen in what condition?

Back 837

HHT

Front 838

malformation of carpals and radial and/or thenar bones, CHD (ASD or VSD) and arrythmyia, TBX5 mutation

Back 838

Holt-Oram Syndrome

Front 839

TBX5 mutation associated with what condition?

Back 839

Holt-Oram Syndrome

Front 840

Noonan Syndrome can be caused by which gene mutations?

Back 840

PTPN11, SOS1, KRAS

Front 841

congenital severe-profound bilateral SNHL and prolonged QT interval, arrhythmia, syncope and sudden death

Back 841

Jervell and Lange-Nielsen

Front 842

condition associated with KCNQ1 and KCNE1 mutations?

Back 842

Jervell and Lange-Nielsen

Front 843

>99% lost in first trimester, dysplastic calvaria with large posterior fontanelle, 3/4 finger syndactyly, ASD, VSD, hydrocephalus, holoprosencephaly, parent of origin effect

Back 843

triploidy

Front 844

If ____ triploidy, have small placenta, severe asymmetric IUGR with large head

Back 844

digynic

Front 845

if __ triploidy, have hydropic large placenta, well grown to mod symmetric IUGR, normal or microcephalic head

Back 845

diandric

Front 846

low birth weight, craniofacial malformations, eye abnormalities, hand/foot defects (aplastic thumb), genital malformations in males, DD, some cases of Rb

Back 846

13q- syndrome

Front 847

leukodystrophy with hypotonia, poor reflexes, tremor, CNS changes on MRI, short stature, craniofacial dysmorphism (deep-set eyes, carp-shaped mouth, microcephaly, prominent ears, midface hypoplasia), limb anomalies (clubfoot, short thumbs), CL/P, GI anomalies, heart anomalies, immunological deficiencies (IgA), eye movement disorders, HL, genital hypoplasia, IQ <70, autism, behavioral problems and seizures

Back 847

18q- syndrome

Front 848

growth and DD, hypotonia, limb anomalies, heart defects, 6-7% spontaneously abort usually early in pregnancy, less than 10 reported liveborns and most die <1yr, caused by dup of chromosomes and failure of cell division in one daughter cell of first post-fertilization cell division or chimerism

Back 848

tetraploidy (92,XXXX or 92,XXYY)

Front 849

BLM is gene mutation in what condition?

Back 849

Bloom Syndrome

Front 850

marfinoid appearance, long slender fingers and toes, crumpled ears, major joint contractures, muscle hypoplasia, kyphosis/scoliosis, severe/lethal, aortic dilation, ASD, VSD, IAA, duodenal or esophageal atresia, malrotation

Back 850

congenital contractural arachnodactyly or Beals Syndrome

Front 851

skin hyperextensibility, widened atrophic scars, joint hypermobility, smooth velvety skin, molluscoid pseudotumors (heaped scar-like over pressure points), subcutaneous spheroids (cyst-like lesions, feel like grains of rice, over bony prominences of legs and arms, fibrosed and calcified fat globules), joint sprains/dislocations/subluxations, hypotonia, easy bruising, hernia, chronic pain, aortic root dilation

Back 851

EDS type I and II (classic)

Front 852

joint hypermobility, soft or velvety skin with normal or slightly increased elasticity, absence of skin or soft tissue fragility, recurrent joint dislocation/subluxation, chronic joint or limb pain, easy bruising, high narrow palate, dental crowding, and low bone density. kids less than 5yo are very flexible and hard to assess. reported instances of aortic root dilation and MVP

Back 852

EDS type III (hypermobility)

Front 853

arterial rupture, intestinal rupture, uterine rupture during pregnancy, FH of vascular EDS. Thin translucent skin, easy bruising, thin lips and philtrum, small chin, thin nose, large eyes, aged hands, small joint hypermobility, tendon/muscle rupture, varicose veins, AV carotid-cavernous sinus fistula, pneumothorax, CHD, clubfoot, gum recession

Back 853

EDS Type IV (vascular)

Front 854

major: friable hyperextensible skin, thin scars, easy bruising, generalized joint laxity, severe muscle hypotonia, progressive scoliosis, scleral fragility and rupture of globe. Minor: widened atrophic scars, marfanoid habitus, rupture of med sized arteries, mild-mod delay of attainment of gross motor milestones

Back 854

EDS Type VI (kyphoscoliotic type)

Front 855

COL3A1 associated with what condition?

Back 855

EDS Type IV

Front 856

PLOD1 associated with what condition?

Back 856

EDS type VI

Front 857

progressive mineralization of skin, eyes, blood vessels and less commonly GI tract. Papules on neck, underarms and joint areas, changes in retina, angioid streaks called Bruch's membrane and bleeding and scarring of retina, arteriosclerosis or claudication (cramping/pain during exercise)

Back 857

pseudoxanthoma elasticum

Front 858

ABCC6 gene mutation associated with what condition?

Back 858

pseudoxanthoma elasticrum

Front 859

COL2A1, COL9A1, COL11A1, COL11A2 all associated with what condition?

Back 859

stickler syndrome

Front 860

___ syndrome is a related syndrome to Stickler and includes short stature

Back 860

Marshall

Front 861

facial asymmetry d/t maxillary and/or mandibular hypoplasia, preauricular or facial tags, ears: microtia (hypoplasia of external ear), anotia, aural atresia (absence of external ear canal), HL, severity range: subtle facial asymmetry with pre-auricular tag to bilat involvement, microtia/anotia w/ atresia of the ear canals, micropthalmia, and respiratory compromise from severe mandibular hypoplasia. other: CL/P, vertebral, cardiac, and limb malformations seen

Back 861

craniofacial microsomia (oculo-auriculo-vertebral) and Goldenhar syndrome

Front 862

Goldenhar syndrome is an issue with development of the ___ and ___ branchial arches

Back 862

1st and 2nd

Front 863

malformed thickened, small nails, hypotrichosis (partial or total alopecia), palmoplantar hyperkeratosis, sometimes HL

Back 863

hidrotic ectodermal dysplasia

Front 864

GJB6 gene mutated in which conditions?

Back 864

nonsyndrome HL and hidrotic ectodermal dysplasia (also called Clouston syndrome)

Front 865

Major: erythema->blister->hyperpigmented streaks->atrophic skin patches. Minor: hypo/andontia, small or malformed teeth, alopecia, woolly hair, nail ridging or pitting, retinal neovascularization causing retinal detachment. MR rare

Back 865

IP (incontentia pigmenti)

Front 866

inheritance of IP?

Back 866

XLD

Front 867

IKBKG/NEMO associated with what condition?

Back 867

IP

Front 868

3 types: 1 (no melanin)- nystagmus, dec iris pigment, foveal hypoplasia, dec visual acuity, strabismus, white hair and skin, translucent iris. 2(some melanin)- milder eye and skin manifestation. 3- ocular problems same as OCA1 but better vision, range of skin and eye pigment from minimal to near normal

Back 868

oculocutaneous albinism

Front 869

TYR and OCA1a/1b/2 associated with what condition?

Back 869

oculocutaneous albinism

Front 870

virilized female, precocious puberty or adrenarche, childhood virilization in males, infant with Na+ losing crisis at birth. Nonclassic form: mod enzyme deficiciency with variable postnatal virilization, no salt wasting, rare cortisol def

Back 870

21-hydroxylase-deficient CAH

Front 871

CYP21A2 gene associated with what condition?

Back 871

21-hydroxylase-deficient CAH

Front 872

affects male sexual development and sex organs. Female external genitalia or ambiguous genitalia or hypospadias/micropenis. Develop some male secondary characteristics, don't develop much facial or body hair, most are infertile. Many raised as girls and about 1/2 adopt a male gender role in adolescence/early adulthood

Back 872

5-alpha-reductase deficiency

Front 873

SRD5A2 associated with what condition?

Back 873

5-alpha-reductase deficiency

Front 874

inheritance of androgen insensitivity syndrome

Back 874

XLR

Front 875

congenital nephropathy, kidney failure by 3yo, Wilms tumor (2yo), gonadal dysgenesis, ambiguous genitalia, high risk for malignancy in gonadal tissues, death d/t renal failure

Back 875

Denys-Drash Syndrome

Front 876

XY individuals with undermasculanized external genitalia, streak gonads, small uterus and fallopian tubes, focal segmental glomeruloscerlosis, gonadoblastoma

Back 876

Frasier syndrome

Front 877

type 1 and 2: hypogonadtropic hypogonadism and anosmia, delayed puberty, mirror hand movement, ataxia, GU anomaly, high palate, pes cavus. type 2: MR, CL/CP, cryptorchidism, choanal atresia, CHD, SNHL

Back 877

Kallman Syndrome Type 1 and 2

Front 878

Klinefelters is caused by _____ meiotic division nondisjunction of either parent, though ___ is > ___ origin

Back 878

1st or second, maternal > paternal

Front 879

inheritance of Lesch-Nyhan

Back 879

XLR

Front 880

HPRT1 is gene associated with what condition?

Back 880

Lesch-Nyhan

Front 881

KAL and FGFR1 are genes associated with what condition?

Back 881

Kallman

Front 882

polyostotic fibrous dysplasia, pathologic Fx, cranial foramina thickening->deafness and blindness, large irregular CAL (coast of Maine pattern), precocious puberty, hyperthyroidism, inc GH, PRL, or PTH, ovarian cysts

Back 882

McCune-Albright Syndrome

Front 883

GNAS associated with what conditions

Back 883

AHO and McCune-Albright Syndrome

Front 884

acute onset adrenal insufficiency (hyperkalemia, acidosis, hypoglycemia, shock), cryptorchidism, delayed puberty. Carrier females: may have adrenal insufficiency or hypogonadotropic hypogonadism

Back 884

X-linked adrenal hypoplasia congenita

Front 885

NROB1 gene associated with what condition?

Back 885

X-linked adrenal hypoplasia congenita

Front 886

HMBS associated with what condition?

Back 886

acute intermittent porphyria

Front 887

thrombocytopenia with intermittent mucosal bleeding, bloody diarrhea, intermittent or chronic petechiae and purpura, eczema, recurrent bacterial/viral infections (esp. ear). If survive infancy, 40% develop 1+ autoimmune disorder. Risk of lymphoma, esp. with exposure to EBV and esp. in rare sites (brain, lung, GI tract), absent or decreased production of WAS protein, XLR inheritance

Back 887

Wiskott-Aldrich Syndrome

Front 888

thrombocytopenia with small platelets but other complications of WAS are mild or absent, some affected individuals have near-normal amounts of WAS protein production, XLR inheritance

Back 888

X-linked thrombocytopenia (XLT)

Front 889

recurrent bacterial infections, persistent neutropenia, and arrested development of bone marrow in absence of other clinical findings of WAS , XLR inheritance

Back 889

X-linked congenital neutropenia (XLN)

Front 890

Type 1: recurrent febrile episodes with peritonitis, synovitis, pleuritis, recurrent erysipelas-like erythema, AA type amyloidosis, favorable response to continuous colchicine treatment, at risk ethnic groups: Armenian, Turkish, Arab, N. African Jewish, Iraqi Jewish, AJ). Type 2: amyloidosis as first clinical presentation

Back 890

familial mediterranean fever

Front 891

MR- mild, immune deficiency, hypertelorism, low-set ears, epicanthal folds, macroglossia, flat nasal bridge; caused by centromeric instability of chromosomes 1,9,16 and rarely 2

Back 891

ICF syndrome

Front 892

DNMT38 associated with what condition?

Back 892

ICF Syndrome

Front 893

recurrent OM, pneumonia, sinusitis <5yrs, sepsis, meningitis, cellulitis, paucity of lymphoid tissue, XLR condition

Back 893

X-linked aggamaglobulinemia

Front 894

BTK associated with what condition?

Back 894

X-linked aggamaglobulinemia

Front 895

inheritance of ICF syndrome

Back 895

AR

Front 896

newborns: feeding difficulties, vomiting, diarrhea, lethargy, hypotonia. If untreated: DD, seizures, coma, incomplete penetrance, AR inheritance

Back 896

3-MCC deficiency

Front 897

often asymptomatic; pigmented sclera, skin darkened in sun-exposed area/around sweat glands, sweat colored brown or urine if exposed to air, ear wax turns red or black, kidney stones and prostate stones in men common, cartilage damage in back/hip/shoulder, valvular heart disease (esp. calcification)

Back 897

alkaptonuria

Front 898

HGD gene associated with what condition?

Back 898

alkaptonuria

Front 899

appear healthy until 2-3mo's when loss of milestones, hypotonia, seizures, FTT occur. Changes of hair (short, sparse, coarse, twisted, lightly pigmented. Temp instability and hypoglycemia may be present in neonatal period. Death by 3yo, XLR condition

Back 899

Menkes

Front 900

type of ATP7A copper transport disorder causing distinctive wedge-shaped calcifications (occipital horns) at sites of attachment of trapezius muscle and sternocleidomastoid muscle to occipital bone. both can have lax skin/joints, bladder diverticula, inguinal hernias, vascular tortuosity, normal intellect.

Back 900

occipital horn syndrome

Front 901

3 clinical forms: lethal neonatal, severe infantile hepatomuscular, myopathic (mild, onset up to adulthood). First 2 severe multisystem dz involving liver failure with hypoketotic hypoglycemia, CM, seizures, early death. Last involves exercise-induced muscle pain and weakness, sometimes with myoglobinuria

Back 901

CPT II deficiency

Front 902

CPT II 2x more likely in which gender?

Back 902

Males

Front 903

gene associated with copper transport disorders

Back 903

ATP7A

Front 904

classic: occurs in males with <1% enzyme activity, period crises of severe pain in extremities, appearance of vascular cutaneous lesons (angiokeratomas), hypohidrosis, corneal and lenticular opacitieis, proteinuria, gradual deterioration of renal function>ESRD, cardiovascular and/or cerebrovascular dz in middle age. variant: males with >1% enzyme activity may have cardiac phenotype (60-70's) w/ L ventricular hypertrophy, mitral insufficiency and/or CM, proteinuria but without ESRD OR renal phenotype (ESRD without skin lesions or pain). Het females have milder symptoms with later onset but may also be asymptomatic or severe, X-linked inheritance, GLA gene

Back 904

Fabry disease

Front 905

GLA gene mutation in what condition?

Back 905

Fabry disease

Front 906

Untreated hets have a 100% risk for development of CAD by age 70yo If male and 75% for females; atherosclerosis, xanthomas, arcus cornae; environmental modifiers and founder effects; hypercholesterolemia at birth ' plasma cholesterole >95th percentile; homozygous FH lethal by 30yo if untreated (600-1000mg/dL LDL)

Back 906

familial hypercholesterolemia

Front 907

LDLR gene mutation associated with what condition?

Back 907

familial hypercholesterolemia

Front 908

benign condition, fructose not broken down and excreted in urine

Back 908

essential fructosuria

Front 909

vomiting, coma, apathy, liver dysfunction, hypoglycemia, hepatosplenomegaly, renal tubular dysfunction when exposed to fructose, FTT<aversion to fruit

Back 909

hereditary fructose intolerance

Front 910

severe hypoglycemia and metabolic acidosis, liver and renal dysfunction in presence of fructose

Back 910

fructose-1,6-BP deficiency

Front 911

ALDOB and FBP1 mutations are associated with what type of conditions?

Back 911

fructose metabolism errors

Front 912

feeding problems, FTT, hepatocellular damage, bleeding sepsis, MR (can be resolved/avoided with early Rx), increased risk for DD, speech problems, motor problems. Females have increased risk of POF.

Back 912

galactosemia

Front 913

GALT associated with what condition?

Back 913

Galactosemia

Front 914

Type 1: clinical/radiographic evidence of bone dz (osteopenia, focal lytic or sclerotic lesions, osteonecrosis), hepatosplenomegaly, anemia and thrombocytopenia, lunc dz, no CNS dz. Type 2: primary neurologic dz, onset before 2yo, limited psychomotor development, rapid progression by 2-4yo. Type 3: same as type 2, but often slower progressive course and may live to 30's-40's. Perinatal Lethal: Icthosiform/collodion skin abnormalities, nonimmune hydrops fetalis. cardiovascular form: calcification of aortic and mitral valve, mild splenomegaly, corneal opacities, supanuclear opthalmoplegia (cardiopulmonary complications seen in all subtypes)

Back 914

Gaucher

Front 915

GBA is associated with what condition?

Back 915

Gaucher

Front 916

hemolytic anemia, neonatal jaundice usually triggered by infection/toxins/drugs; heterozygote advantage to malaria; severity depends on mutation (thus more common in places with malaria like Africa, Mediterranean, Asia), XLR inheritance

Back 916

Glucose-6-P dehydrogenase deficiency

Front 917

inheritance of glucose-6-P dehydrogenase deficiency

Back 917

XLR

Front 918

Classic: Infantile-onset, Presentation: hypotonia, generalized muscle, cardiomegaly, HCM, feeding difficulties, FTT, respiratory distress, and hearing. With ERT, results in death in 1yo from progressive L ventricular outflow obstruction. Non-classical Variant: presents within first year of life with motor delays and/or slowly progressive muscle weakness, typically resulting in death from ventilator failure in early childhood. cardiomegaly can be seen but heart dz not a major source of morbidity. Late-onset: childhood/juvenile/adult-onset. characterized by proximal muscle weakness and respiratory insufficiency without cardiac involvement.

Back 918

GSD II (Pompe)

Front 919

GAA gene associated with what condition?

Back 919

Pompe disease

Front 920

mutation in glycogen debrancher enzyme, hypoglycemia, hepatomegaly, hyperlipidemia, muscle weakness, death by 2yo, heart failure

Back 920

Type III GSD (Cori's Dz/Forbes Dz)

Front 921

glycogen brancher enzyme mutation, hepatosplenomegaly, cirrhosis, FTT, death by 5yo

Back 921

type IV GSD (Andersen disease)

Front 922

muscle glycogen phosphorylase mutation, exercise-induced muscle cramps and weakness, rhabdo, growth retardation, hemolytic anemia

Back 922

Type V GSD (McArdle disease)

Front 923

phosphorylase kinase mutation, hyperlipidemia, delayed motor development, growth retardation

Back 923

Type IX GSD

Front 924

glucose transport GLUT2 mutation, hypoglycemia, hepatomegaly

Back 924

type XI GSD (Fanconi-Bickel syndrome)

Front 925

aldolase A defect, exercise intolerance, cramps

Back 925

type XII GSD (red cell aldolase deficiency)

Front 926

beta-enolase defect, exercise intolerance, cramps

Back 926

GSD type XIII

Front 927

glycogen synthase defect, occasional muscle cramping, does not result in issues with liver

Back 927

type 0 GSD

Front 928

All GSD's are what inheritance?

Back 928

AR

Front 929

affects visceral P/A/C nervous systems, more common in women, abdominal pain sign of acute attack (N/V, constipation/diarrhea, abdominal distention, ileus, urinary retention, incontinence, dysuria. Peripheral neuropathy can cause weakness in arms/legs; motor neuropathy may involve cranial nerves. permanent quadriplegia may occur after a severe attack; psychiatric (insomnia, delirium, somnolence, coma), death may occur from paralysis of resp muscles or cardiovascular failure, risk factors for crises: fasting, stress, infection, strenuous exercise, hormone fluctuations, exposures

Back 929

hydroxymethylbilane synthase deficiency (HMBS)

Front 930

inhertance of HMBS?

Back 930

AD

Front 931

hypoketotic hypoglycemia, vomiting, lethargy, seizures, coma, death, hepatomegaly, liver disease, 3-24 mo's presentation

Back 931

MCAD

Front 932

most asymptomatic, can have FTT, metabolic acidosis ketotic hypoglycemia, DD, seizures, neuromuscular symptoms

Back 932

SCAD

Front 933

accumulation of heparan sulfate, DD, hyperactivity, spasticity, motor dysfunction, death by 2nd decade, severe neurological symptoms

Back 933

MPS III (Sanfilippo syndrome)

Front 934

accumulation of keratin sulfate and chondroiten 6-sulfate, severe skeletal dysplasia, short stature, motor dysfunction, normal IQ

Back 934

MPS IV (morquio syndrome)

Front 935

accumulation of dermatan sulfate, severe skeletal dysplasia, short stature, motor dysfunction, kyphosis, heart defects, normal IQ

Back 935

MPS type VI (Maroteaux-Lamy Syndrome)

Front 936

accumulation of heparin, dermatan and chondroitin 6-sulfate, hepatomegaly, skeletal dysplasia, short stature, corneal clouding and DD

Back 936

MPS VII (Sly Syndrome)

Front 937

accumulation of hyaluronic acid, soft-tissue masses around joints with swelling, mild facial changes, short stature, normal joint movement, normal IQ

Back 937

MPS IX (Natowicz Syndrome)

Front 938

types of abnormalities caused by accumulation of hyaluronate?

Back 938

synovial fluid, articular cartilage, skin, vitreous humor, ECM of loose connective tissue

Front 939

types of abnormalities caused by accumulation of chondroitin sulfate?

Back 939

cartilage, bone, heart valves

Front 940

types of abnormalities caused by accumulation of heparan sulfate?

Back 940

basement membranes, components of cell surface

Front 941

types of abnormalities caused by accumulation of heparin?

Back 941

component in mast cells, lining of arteries of lungs, liver and skin

Front 942

types of abnormalities caused by accumulation of dermatan sulfate?

Back 942

skin, blood vessels, heart valves, tendons, lungs

Front 943

types of abnormalities caused by accumulation of keratan sulfate?

Back 943

cornea, bone, cartilage aggregated with chondroitin sulfates

Front 944

maple syrup odor of urine within 12-24 hrs of birth, increased plasma concentrations of branched chain AA (leu, isoleu, val), ketonuria, irritability, poor feeding, progressive encephalopathy (lehtargy, stereotyped movements, coma, death), inc risk for ADHD, depression, anxiety in adolescents and adults

Back 944

MSUD

Front 945

BCKDHA associated with what condition?

Back 945

MSUD

Front 946

slowly progressive, fatal in early childhood. Postnatal growth limited and ceases at 2yo, contractures, thickened skin, coarse facial features, hypertrophic gingival, orthopedic abnormalities (thoracic deformity, kyphosis, clubfeet, deformed long bones, dislocation of hips) cardiac (thickening and insufficiency of mitral valve and less commonly aortic valve), mucosal thickening narrows airways, stiffening of thoracic cage leading to death, XLR condition

Back 946

mucolipidosis II (I-Cell disease)

Front 947

GNPTAB gene associated with what conditions?

Back 947

I-cell disease and mucolipidosis type III

Front 948

slow growth rate, mild to mod dysostosis multiplex, joint stiffness and pain initially in shoulders/hips/fingers, gradual coarsening of facial features (normal to mildly impaired), organomegaly is mild, pain from osteoporosis in childhood becomes more severe with age, cardiorespiratory complications (restrictive lung dz, thickening/insufficiency of mitral and aortic valves, left ventricular hypertrophy) are common causes of death in early to mid-adulthood

Back 948

mucolipidosis type III

Front 949

3 types.C: Lipid storage disease (present in infants, children or adults), ascites, severe liver dz, respiratory failure or hypotonia and DD, ataxia, gaze palsy, dementia, dystonia and seizures, dysarthria and dysphage, death 2nd/3rd decade. A: neuronopathic with death <3yo d/t frequent resp. infections and failure, hepatosplenomegaly, psychomotor development stops at 12mo's, classic cherry red spot of macula of retina. B: Non-neuronopathic, later onset and mild, hepatosplenomegaly with progressive hypersplenism, stable liver dysfunction, deterioration of lung function and atherogenic lipid profile, survival to adulthood

Back 949

Niemann-Pick

Front 950

general category of disease involving secretion of non-aa's in urine. A few days after birth: toxic encephalopathy (vomit, poor feeding, seizures, abnormal tone, lethargy, coma), biochemical features: acidosis, ketosis, inc ammonia, dec glucose, neutropenia, abnl liver fx

Back 950

organic acidemia symptoms

Front 951

without dietary restriction of phenylalanine, impaired brain development (microcephaly, seizures, MR, behavioral problems)

Back 951

PKU

Front 952

type 1 (more common in French canadian pop): most severe, sx appear in first few months, FTT, diarrhea, vomiting, jaundice, cabbage-like odor, increased tendency to bleed, leads to liver/kidney failure, CNS problems, inc risk of liver cancer. Type 2: affects eyes, skin, mental development, sx begin early childhood, excess tearing, photophobia, eye pain and rednesss, painful skin lesions on palms and soles, 50% have ID. type 3: ID, seizures, periodic loss of balance and coordination

Back 952

tyrosinemia

Front 953

general category of disease involving appearing normal at first but then rapid development of cerebral edema, lethargy, anorexia, hyper/hypo-ventilation, hypothermia, seizures, coma. Initial symptoms include feeding problems, low core temp, somnolence. In milder or partial defects, sx may develop later and be more subtle, occurring when under stress. CPSI and OTC more severe. 15% of carrier females develop herpammonemia during their lifetime. ARG is more subtle dz with neurologic involvement and growth affected

Back 953

urea cycle disorders

Front 954

All urea cycle disorders are ___ inheritance except for ____

Back 954

AR, OTC (X-linked)

Front 955

scaling of skin, esp. on neck, trunk, lower extremities, 4mm scales and can be dark brown or gray, may subside in summer, variable onset from a few hours after birth to up to a year in milder cases, corneal opacities may be present but don't affect vision, cryptorchidism present in some affected individuals (probably d/t deletion of nearby genes), larger dels that include SHOX gene can result in short stature and dels including KAL1 gene can lead to hypogonadotrophic hypogonadism (Kallman Syndrome). female carriers may have difficulty during childbirth since defective protein expressed in placenta

Back 955

X-linked icthyosis/steroid sulfatase deficiency (STS)

Front 956

inheritance of STS

Back 956

XLR

Front 957

3-12mo's onset often following a viral infection. Decompensation w/ lactic acidosis during illness associated with psychomotor retardation or regression (75% by 2-3yo,usually d/t respiratory or cardiac failure), hypotonia, spasticity, chorea, cerebellar ataxia, peripheral neuropathy, hypertrophic CM, mitochondrial inheritance

Back 957

Leigh Syndrome

Front 958

proximal neurogenic muscle weakness with sensory neuropathy, ataxia, pigmentary retinopathy. onset (ataxia, LD) in early childhoood. can be stable then suffer episode deterioration with viral illness, mitochondrial

Back 958

NARP

Front 959

early psychomotor development normal but short stature common, 2-10yo first symptoms, tonic-clonic seizures, recurrent headaches, anorexia, recurrent vomiting, may be exercise intolerance or proximal limb weakness, seizures associated with stroke-like episodes of transietn hemiparesis or cortical blindness, may be associated with altered consciousness and may be recurrent. SNHL is common. , mitochondrial

Back 959

MELAS

Front 960

A3243G common mutation associated with what mitochondrial condition?

Back 960

MELAS

Front 961

multisystem disorder defined by onset <20yrs and pigmentary retinopathy and progressive external opthalmoplegia, cardiac conduction block, elevated CSF protein, concentration or cerebellar ataxia in infancy, due to mitochondrial deletion

Back 961

Kearns-Sayre Syndrome (KSS)

Front 962

sideroblastic anemia and exocrine pancreas dysfunction, usually lethal in infancy, mitochondrial deletion

Back 962

Pearson syndrome

Front 963

ptosis, paralysis of extraocular muscles, variably severe proximal limb weakness and relatively benign, mitochondrial

Back 963

progressive external opthalmoplegia (PEO)

Front 964

progressive GI dysmotility and cachexia manifesting as early satiety, nausea, dysphagia, GI reflux, postprandial emesis, episodic abdominal pain and/or distention and diarrhea. HL, ptosis/opthalmoplegia or opthalmoparesis, demyelinating peripheral neuropathy manifesting as paresthesias (tingling, numbness, pain), symmetric and distal weakness

Back 964

MNGIE

Front 965

myopathy, dementia, myoclonic seizures, ataxia, deafness, abnormal brainstem evoked responses, SNHL, ataxia, renal dysfunction, diabetes, CM; course can be slowly progressive or rapidly downhill

Back 965

MERRF

Front 966

A1555G mutation is associated with what condition?

Back 966

predisposition to aminoglycoside ototoxicity

Front 967

A7443G/A7444G/A7445G are mutations associated with what condition?

Back 967

childhood onset of SNHL and palmoplantar keratodermia in some families

Front 968

with CL/P, which side of the face is affected 2x more if unilateral?

Back 968

left

Front 969

type of spina bifida without symptoms with only a dimple or tuft of hair

Back 969

occulta

Front 970

type of spina bifida with protruding meninges and CSD with spinal cord and roots in normal position

Back 970

cystic with meningocele

Front 971

type of spina bidida with protruding meninges, CSF, spinal cord and/or nerve roots, more severe and often results in neurological deficits, secondary hydrocephalus, poor prognosis with Arnold-Chiari malformations

Back 971

meningomyelocele

Front 972

lack of fetal movement in utero, lack of muscular development and growth in newborn with contracture and deformity at most joints, immobility of one or more joints of limbs (generally asymmetric) and dating from intrauterine life. 2/3 able to walk with or without braces and attend school, normal IQ

Back 972

amyoplasia congenita/arthrogyposis multiplex congenita

Front 973

cause of arthrogyposis multiplex congenita

Back 973

lack of amniotic fluid or bicornuate uterus or maternal fever or virus during pregnancy

Front 974

corpus callosum missing, colboma, MR, micropthalmia, seizures, retinal lesions, affects only girls

Back 974

Aicardi Syndrome

Front 975

progressive loss of cognitive function, agitation, social withdrawal, hallucinations, seizures, myoclonus, parkinsonian features; death from malnutrition, infection, or heart disease, multifactorial inheritance

Back 975

Alzheimer disease

Front 976

severe DD or MR, severe speech impairment, gait ataxia and/or tremulousness of limbs, inappropriate happy demeanor that includes frequent laughing, smiling, excitability, microcephaly, seizures, love water

Back 976

Angelman syndrome

Front 977

UBE3A associated with what condition?

Back 977

Angelman Syndrome

Front 978

general symptoms of this condition include vision problems, seizures, personality and behavior changes, slow learning, clumsiness, stumbling, mental impairment, worsening seizures, progressive loss of sight and motor skills and die by teens/20's, caused by buildup of lipofuscins

Back 978

Batten Syndrome/neuronal ceroid lipofuscinosis

Front 979

inheritance of Batten syndrome

Back 979

AR

Front 980

Stroke-like episodes before age 60, cognitive disturbances, behavioral abnormalities, migraine with aura, AD condition, mutation in NOTCH3

Back 980

CADASIL (cerebral AD arteriopathy with subcortical infarcts and leukoencephalopathy)

Front 981

NOTCH3 mutation associated with what condition?

Back 981

CADASIL

Front 982

macrocephaly, lack of head control, DD by 3-5 mo, severe hypotonia, never sit, walk or speak. Hypotonia evolves to spasticity; life expectancy to teens

Back 982

canavan disease

Front 983

ASPA gene associated with what condition?

Back 983

canavan disease

Front 984

progressive, Gi dysfunction, vomiting crises, recurrent pneumonia, altered sensitivity to pain and temp, CV instability, autonomic crises, hypotonia, broad based ataxia gate deteriorates, decreased life expectancy, Dec taste and absence of fungiform papillae of tongue, dec or absent DTR's, absence of overflow tears with crying, mutation in IKBKAP gene

Back 984

familial dysautonomia

Front 985

IKBKAP gene associated with what condition?

Back 985

familial dysautonomia

Front 986

infantile form: irritability to sensory stimuli, muscle hypertonicity, progressive neurologic deterioration, peripheral neuropathy, white matter disease, elevated CSF protein. Later onset: weakness, vision loss, IQ regression, mutation in GALC gene

Back 986

Krabbe disease

Front 987

GALC mutation associated with what condition?

Back 987

Krabbe disease

Front 988

bradykinesia, rigidity, tremor, asymmetric limb involvement. Juvenile onset: AR PARK2 mutations, typical features, onset 20-40yo

Back 988

Parkinson disease

Front 989

PARK2 associated with what condition?

Back 989

Parkinson's

Front 990

inheritance of PD?

Back 990

AD, AR, multifactorial

Front 991

abnormal development of optic disk, pituitary deficiencies, agenesis of septum pallucidum (separates anterior horns or lateral ventricles of brain), blindness in one or both eyes, pupil dilation with light, hypotonia, hormonal problems, seizures, jaundice at birth, ID or normal IQ

Back 991

septo-optic dysplasia (de Mortsier's syndrome)

Front 992

HESX1, OTX2, and SOX genes associated with what condition?

Back 992

septo-optic dysplasia

Front 993

liver disease: jaundice, self-limited hepatitis-like illness, autoimmune hep, hepatic failure, chronic liver disease. Neurological: movement disorder, disorganziation of personality, Keyser Fleischer rings

Back 993

Wilson disease

Front 994

childhood cerebral: ADHD->total disability within 2 yrs; adrenomyeloneuropathy: late 20's progressive paraparesis, sphincter disturbance, adrenocortical dysfunction; adrenocortical insufficiency only: majority by age 7.5 (seen in 20% of carrier females)

Back 994

X-linked adrenoleukodystrophy

Front 995

ABCD1 gene associated with what condition?

Back 995

X-linked adrenoleukodystrophy

Front 996

port-twin stain on face usually, seizures, paralysis or hemihypotonia, LD

Back 996

Sturge-Weber

Front 997

UMN: hyperreflexia, extensor plantar response, inc muscle tone, weakness. LMN: weakness, muscle wasting, hyporeflexia, muscle cramps, fasciculations. Frontotemporal dimentia, mutations in SOD1 mostly, AD inheritance

Back 997

ALS

Front 998

SOD1 associated with what condition?

Back 998

ALS

Front 999

genetic heterogeneity; progressive distal weakness, distal muscle wasting, hyporeflexia, abnormal gait, dropped foot, foot deformities (hammer toes, pes cavus), loss of balance, weakness of hand muscles, clawhand deformity, decreased or absent reflexes

Back 999

CMT1A

Front 1000

PMP22 associated with what 2 neurological conditions?

Back 1000

CMT1A (dup or other mutation), HNPP (deletion)

Front 1001

adult with recurrent focal pressure palsies, mild polyneuropathy, absent ankle reflexes, reduced DTR's, mild-mod pes cavus deformity, PMP22 deletion

Back 1001

HNPP

Front 1002

proximal limb weakness, difficulty running and walking, calf hypertrophy, onset 3-15yo (68% childhood, 10% adult), different types but most AR

Back 1002

limb-girdle muscular dystrophy

Front 1003

DMPK gene associated with what condition?

Back 1003

myotonic dystrophy type I

Front 1004

weakness, hypotonia, depressed or absent DTR's, weakness usually in face most, neck flexors, proximal limb muscles, many times of onset, AR or AD, disorder of thin filament anchoring proteins

Back 1004

Nemalin myopathy

Front 1005

gradually progressive neuromuscular disorder d/t degeneration of LMN, results in proximal muscle weakness, muscle atrophy, fasciculation, gynecomastia, testicular atrophy, reduced fertility d/t mild androgen insensitivity, XLR inheritance, androgen receptor gene mutation

Back 1005

spinal and bulbar muscular atrophy

Front 1006

androgen receptor (AR) gene associated with what condition?

Back 1006

spinal and bulbar muscular atrophy

Front 1007

many types based on onset, muscle weakness, tongue fasciculations, absent deep tendon reflexes, hypotonia, frequent falls, SMN1 and 2 gene mutations with modifier SMN2

Back 1007

SMA

Front 1008

slowly progressive incoordination of gait, poor coordination of hands, speech, and eye movement, atrophy of cerebellum, 28 subtypes based on inheritance and causative gene, most subtypes CAG repeat expansions, AD inheritance

Back 1008

spinocerebellar ataxias

Front 1009

inheritance of SMA

Back 1009

AR

Front 1010

inheritance of spinal and bulbar muscular atrophies

Back 1010

XLR

Front 1011

inheritance of spinocerebellar ataxia

Back 1011

AD with trinucleotide repeats

Front 1012

skeletal muscle issues and poor reactions to meds, RYR1 gene mutation

Back 1012

multicore and central core myopathies

Front 1013

pain during exercise and difficulty walking, error in gene involved in vesicle movement through cell (DNM2 gene)

Back 1013

myotubular myopathy

Front 1014

myopathy d/t fiber size variation causing weakness in shoulder, upper arms, thighs and hips, type 1 fibers (slow twitch) smaller than type 2 (fast twitch)

Back 1014

congenital fiber type disproportion

Front 1015

most severe form of congenital muscular dystrophy with most children dying before 3yo, generalized hypotonia, muscle weakness, DD with MR and occasional seizures, type II cobblestone lissencephaly, hydrocephalus, cerebellar malformation, eye abnormalities and congenital muscular dystrophy with hypoglycosylation of alpha-dystroglycan, AR inheritance

Back 1015

Walker-Warburg

Front 1016

POMT1 and 2, FKRP genes associated with what condition?

Back 1016

Walker-Warburg

Front 1017

progressive degenerative disease of macula, region of retina responsible for central vision; drusen (protein accumulation) and retinal dtachment seen (d/t bleeding under retina or neovascularization), complement factor H mutations

Back 1017

age-related macular degeneration

Front 1018

visual condition associated with loss of central vision, mutation in ABC4 gene

Back 1018

Stargardt's

Front 1019

prenatal and postnatal overgrowth; macroglossia, omphalocele, viseromegaly, embryonal tumor in childhood, hemihyperplasia, renal abnormalities, adrenocortical cytomegaly, neonatal hypoglycemia; 20% mortality

Back 1019

beckwith-wiedemann syndrome

Front 1020

classic: macrocephaly, pointed chin, tall stature and increased body mass, delayed motor kills, delayed cognitive, verbal, and social development, advanced BA. Less common: phobias, aggression, OCD, ADD, abnormal EEG and seizure, chronic OM and constipation, congenital heart defects, strabismus, hyper/hypothyroidism, possible increased risk of tumors (saccrococcygeal teratoma and neuroblastoma)

Back 1020

Sotos syndrome

Front 1021

NSD1 associated with what condition?

Back 1021

Sotos Syndrome

Front 1022

distinctive craniofacies (macrocephaly, ocular HTN, macrostoma, macroglossia, palatal abnormalities), variable: supernumary nipples, diastasis recti/umbilical hernia, congenital heart defects, renal defects (nephromegaly, multicystic kidneys, hydronephrosis, hydroureter, duplicated ureters) and GI anomalies (pyloric ring, Meckel's diverticulum, intestinal malrotation, hepatosplenomegaly, polysplenia), skeletal (vertebral fusion, scoliosis, pectus, rib abnormalities, winged scapula, congenital hip dislocation), hands (large, broad thumbs, brachydactyly, syndactyly, clinodactyly, postaxial polydactyly), tumor frequeny=10% (Wilms tumor, hepatoblastoma, adrenal neuroblastoma, gonadoblastoma, hepatocellular carc), XLR condition, GPC3 mutation

Back 1022

Simpson-Golabi-Behmel Syndrome

Front 1023

GPC3 gene associated with what 2 conditions?

Back 1023

Simpson-Golabi-Behmel Syndrome and Weaver Syndrome

Front 1024

macrocephaly, dysmorphic facial features (prominent forehead, flat occiput, broad forehead with frontal bossing, hypertelorism, broad flat nasal bridge, long and accentuated philtrum, micrognathia, large and dysplastic ears), accelerated skeletal maturation, limb anomalies and skeletal anomalies, DD, and predisposition for tumors, cardiovascular anomalies, hypotonia or hypertonia, DD, tumors, large hands with broad thumbs and prominent finger pads, camptodactyly, clinodactyly, nails thin. Normal life span, AD

Back 1024

Weaver syndrome

Front 1025

inheritance of Simpson-Golabi-Behmel Syndrome?

Back 1025

XLR

Front 1026

manifestations precipitated by certain volatile anesthetics which release calcium stores causing skeletal muscle contracture, glycogenolysis, increased cell mtabolism, excess heat and lactate production, acidosis, hypercapnia, tachycardia, hypoxemia, rhabdomyolysis, increased serum CK, risk of cardiac arrhythmia/arrest, myoglobinuria with risk of renal failure. first symptoms occur in OR or postop, but may result from exercise or exposure to hot environments. death results without prompt treatment.

Back 1026

malignant hyperthermia susceptibility

Front 1027

RYR1 and CACNA1s mutations lead to what condition?

Back 1027

malignant hyperthermia susceptibility

Front 1028

meyelosuppression, increased risk of brain tumor in TPMT-deficient patients with acute lymphoblastic leukemia receiving brain irradiation

Back 1028

thiopurine S-methyltransferase deficiency

Front 1029

slowly progressive cerebellar ataxia, f/b oculomotor apraxia and severe primary motor peripheral axonal motor neuropathy. Oculomotor apraxia progresses to external opthalmoplegia, AR, more in Portugal and Japan, APTX and SETX gene mutations

Back 1029

ataxia with oculomotor apraxia type 1 and 2

Front 1030

APTX and SETX genes associated with what condition?

Back 1030

ataxia with oculomoter apraxia type 1 and 2

Front 1031

Type 1: normal prenatal growth, severe FTT in first 2 yrs, progressive deterioration of vision, hearing, CNS, PNS. Type II: growth failure at birth, little or no postnatal neurological development, kyphosis, scoliosis, joint contracture. Type III: normal growth and development or late onset. XP-CS: facial freckling, early skin cancer, MR, spasticity, short stature, hypogonadism (no demyelination). Death in 1st-2nd decade Type I, 7yo Type II. , d/t abnormal transcription-coupled nucleotide excision repair, ERCC6 and ERCC8 mutations, AR inheritance

Back 1031

Cockayne Syndrome

Front 1032

ERCC6 and ERCC* associated with what condition?

Back 1032

cockayne syndrome

Front 1033

grow normally until puberty then stop growing and have short stature, graying and loss of hair, hoarse voice, thin/hardened skin, bird-like facial appearance, thin arms and legs and thick trunk due to abnormal fat deposition (all this in 20's). Then get cataracts, skin ulcers, type 2 DM, diminished fertility, atherosclerosis, osteoporosis, cancer. Die 40's/50's., AR inheritance, seen more in Japan

Back 1033

Werner syndrome

Front 1034

inheritance of Hutchinson-Gilford progeria syndrome

Back 1034

AD, all de novo

Front 1035

WRN gene associated with what condition?

Back 1035

Werner syndrome

Front 1036

variable expressivity or tissue-specific expression of mutations; progressive pulmonary disease, exocrine pancreatic insufficiency, obstructive azoospermia (d/t CBAVD), elevated sweat chloride concentration, growth failure, meconium ileus

Back 1036

CF

Front 1037

spectrum from progressive renal disease with cochlea and ocular abnormalities (Alport) to isolated hematuria with benign course (thin BM nephropathy). ESRD: 60% by 30yo and 90% by 40yo and deafness: 80-90% SN deafness by age 40 in males, later in females with XL Alport. Renal progression and deafness is slower in AD alport and ocular lesions uncommon. Juvenile onset HL

Back 1037

aplort syndrom and thin BM nephropathy

Front 1038

inheritance of alport's

Back 1038

XLR, AR

Front 1039

COL4A3-5 associated with what condition

Back 1039

Alport condition

Front 1040

enlarged echogenic kidneys, 45% liver abnormalities, hepatomegaly, dilated intrahepatic biliary ducts, increased echogenicity, pulmonary hypoplasia from oligohydramnios, 30% neonates die from resp. insufficinecy, 50% have ESRD in 1st decade of life, 15-yr survival rate 67-79%, AR, PKHD1 gene mutation

Back 1040

AR polycystic kidney disease

Front 1041

PKHD1 associated with what condition

Back 1041

polycystic kidney disease (AR)

Front 1042

progressive renal failure, renal and hepatic cysts, intracranial saccular aneurysms (5-10%), mitral valve prolapse (25%), colonic diverticula (common); HTN as secondary effect, ESRD by 60yo (50%), recurrent UTI's, other cysts (pancreatic, hepatic, ovarian, splenic). some mutations show later onset and slower rate of progression. AD

Back 1042

polycystic kidney disease

Front 1043

multiple joint contractures in whole body ; lack of fetal movement causes extra connective tissue to develop around joint resulting in fixation of joint limiting movement and aggravating joint contracture; more severe when Dx'd early in pregnancy. 50% with limb involvement and CNS dysfunction die in first year of life, numerous inheritance types

Back 1043

arthrogyposis or arthrogyposis multiplex congenita

Front 1044

abnormalities of skeletal and reproductive systems: skeletal- bowing of long bones, short legs, dislocated hips, underdeveloped shoulder blades, 11 rib pairs (not 12), club feet, neck abnormalities, ambiguous genitalia (75% of those XY have ambiguous genitalia or normal female genitalia), internal organs can be both, facies: micrognathia, prominent eyes, flat face, relative microcephaly, Pierre-Robin sequence (cleft palate, glossoptosis, micrognathia), weakened cartilate in URT (laryngotracheomalacia), blocks airways, difficulty breathing. few survive past infancy, abnormality of SOX9 gene, AD inheritance

Back 1044

camptomelic dysplasia

Front 1045

the type of camptomelic dysplasia without bowed limbs is called what?

Back 1045

acamptomelic camptomelic dysplasia

Front 1046

delayed closure of cranial sutures, hypoplastic or aplastic clavicles, multiple dental abnormalities. Abnormally large wide open anterior fontanel, midface hypoplasia, brachydactyly, recurrent OM, HL, normal intellect, RUNX2 gene mutation, AD inheritance

Back 1046

cleidocranial dysplasia

Front 1047

RUNX2 gene associated with what condition?

Back 1047

cleidocranial dysplasia

Front 1048

In terms of FGFR-related craniosynostoses, all but ___and ______are associated with bicoronal craniosynostosis or cloverleaf skull, distinctive facial features, variable hand/foot anomalies (broad and/or syndactylous). DD/MR, HL, and visual impairment common

Back 1048

Muenke and FGFR2-related isolated coronal craniosynostoses

Front 1049

abnormal joining (fusion) of 2 or more cervical vertebrae which leads to a short neck, limited ROM in neck, low hairline at back of head. Can develop spinal stenosis over time, osteoarthritis, scoliosis, hearing difficulties, GU abnormalities like malformed kidneys, NTD, cleft palate, hart abnormalities, underdeveloped shoulder blades that sit abnormally high on back (Sprengel deformity), GFD6 and 3 mutations, AD

Back 1049

Klippel-Fiel

Front 1050

GFD3 and 6 are associated with what condition?

Back 1050

Klippel-Fiel

Front 1051

Exostoses (benign cartilate-capped bony growths) arising from growth plate of long bones or from surface of flat bones (scapula). Limb length inequity and bowed long bones can develop. Short metacarpals. Can have mass effect compression of nerves and blood vessels. growth ceases after skeletal maturation and 0.5-2% degenerate to chondrosarcoma

Back 1051

multiple exostoses syndrome

Front 1052

ExT1 and 2 mutations are associated with what condition?

Back 1052

multiple exostoses syndrome

Front 1053

inheritance of multiple exostoses syndrome?

Back 1053

AD

Front 1054

coronal synostosis, facial asymmetry, ptosis, 2/3 hand syndactyly, mild-mod DD in a minority, short stature, parietal foramina, vertebral fusions, radioulnar synostosis, cleft palate, maxillary hypoplasia, congenital heart defect, TWIST1 mutation, AD inheritance

Back 1054

Saethre-Chotzen Syndrome

Front 1055

IUGR, growth retardation, microcephaly with MR, facial features (large eyes, beak-like nose, narrow face, receding lower jaw), chromosome breakage (25%), AR inheritance

Back 1055

Seckel Syndrome or microcephalic primordial dwarfism

Front 1056

SCKL1,2,3 are associated with what condition?

Back 1056

Seckel syndrome

Front 1057

inheritance of Seckel Syndrome

Back 1057

AR

Front 1058

hypertelorism, shawl scrotum, brachydactyly, short stature, cryptorchidism, cervical vertebral abnormalities, MR (30%), milder manifestations in females, XLR inheritance, FGD1 gene mutation

Back 1058

AARSKOG syndrome

Front 1059

inheritance of AARSKOG syndrome

Back 1059

XLR

Front 1060

FGD1 associated with what condition?

Back 1060

AARSKOG syndrome

Front 1061

ambiguous genitalia, enlarged cystic ovaries, poor masculinization in males, maternal virilization during pregnancy with affected fetus, craniosynostosis, choanal stenosis or atresia, stenotic external auditory canals, hydrocephalus, neonatal fractures, bowing of long bones, joint contracture, renal malformations, AR inheritance, POR gene, caused by steroid and cholesterol synthesis issue

Back 1061

Antley-Bixler Syndrome

Front 1062

inheritance of Antley-Bixler syndrome

Back 1062

AR

Front 1063

POR is gene associated with what condition?

Back 1063

Antley-Bixler

Front 1064

EYA1 and SIX1 are associated with what condition?

Back 1064

branchiootorenal syndrome (BOR)

Front 1065

ocular coloboma (bilat), anomalies of heart/kidneys/anus, preauricular tags/pits, downward PF, hypertelorism, MR mild, prenatal growth delays

Back 1065

Cat Eye Syndrome

Front 1066

Cat Eye syndrome is a trisomy or tetrasomy of what chromosome?

Back 1066

22q11

Front 1067

pleiotropy; Coloboma of iris/retina/optic disc/optic nerve; Heart defect; Atresia of choanae; Retardation of growth and development; Genital abnormalities; ear anomalies; Facial Palsy; Cleft lip; Tracheoesophageal fistula; perinatal and infant mortality 50%, CHD7 gene, AD inhertiance, helicase DNA-binding issues

Back 1067

CHARGE syndrome

Front 1068

CHD7 gene associated with what condition?

Back 1068

CHARGE syndrome

Front 1069

severe to profound MR in males, short, soft, fleshy hands, tapering fingers with small terminal phalanges, males <3% in height, microcephaly, stimulus induced drop episodes, kyphoscoliosis, characteristic facial features in older males (prominent forehead, widely spaced and downward-slanting eyes, short nose with wide tip, wide mouth and full lips), normal to profound Mr in females, RPS6KA3 gene mutation, XLD inheritance

Back 1069

Coffin-Lowry Syndrome

Front 1070

inheritance of Coffin-Lowry Syndrome?

Back 1070

XLD

Front 1071

RPS6KA3 associated with what condition?

Back 1071

Coffin-Lowry Syndrome

Front 1072

DD, ID, microcephaly, hypotonia, myopia, retinal dystrophy, hypermobility, distinctive facial features (thick hair and eyebrows, long eyelashes, down-slanting and wave-shaped eyes, bulbous nasal typ, smooth philtrum, prominent upper central teeth), neutropenia, overly friendly, obesity in torso, narrow hands and feet, slender fingers, AR inheritance

Back 1072

Cohen Syndrome

Front 1073

COH1 and VPS13B associated with what condition?

Back 1073

Cohen Syndrome

Front 1074

Cohen Syndrome has what inheritance?

Back 1074

AR

Front 1075

pre/postnatal growth retardation, low anterior hairline and synophrys, diaphragmatic hernia, upper limb anomalies- hypoplastic middle phalanx of index finger and hypoplatic thenar eminense), ptosis, nystagmus, mod-severe MR, pulmonary valve stenosis and/or VSD, NIPBL mutations, AD and XLR inheritance

Back 1075

Cornelia de Lange Syndrome

Front 1076

NIPBL and SMC1L1 gene associated with what condition?

Back 1076

Cornelia de Lange Syndrome

Front 1077

inheritance of Cornelia de Lange Syndrome

Back 1077

AD or XLR

Front 1078

LGA, coarse face, CL/CP, diaphragmatic defect, distal digital hypoplasia, MR in survivors, agensis of CC, optic and olfactory tract hypoplasia, GU malformation; majority stillborn or die in early neonatal period and 14% survive, AR inheritance

Back 1078

Fryns Syndrome

Front 1079

macrocephaly, ocular hypertelorism, preaxial polydactyly, cutaneous syndactyly, DD, MR, seizures (<10%) and more common with large deletions. Allelic with Pallister-Hall syndrome (GLI3 frame-shifting mutation), AD

Back 1079

Greig Cephalopolysyndactyly

Front 1080

ventral forebrain maldevelopment (alobar-63% and severe- or semilobar -28%-and lobar-9% and more mild), facial dysmorphism (cyclopia to normal and reflects severity of CNS malformations; microcephaly or macrocephaly, anopthalmia, microphthalmia, hypotelorism or hypertelorism, dysmorphic nose, palatal anomalies, bifid uvula, single central incisor, absence of superior labial frenulum), DD (also reflective of CNS malformation), associated with SHH mutations, AD inheritance

Back 1080

holoprosencephaly (nonsyndromic)

Front 1081

SHH associated with what condition?

Back 1081

holoprosencephaly (nonsyndromic)

Front 1082

TS18, triploidy, maternal UPD for chromosome 7 or 14, TS 21; haploinsufficiency of the short arm of chromosome 4 (p15.1p15.32) associated with this phenotype____?

Back 1082

IUGR

Front 1083

hypotonia in infancy leading to ataxia later, DD/MR, alternating tachypnea and/or apnea, pigmentary retinopathy, oculomotor apraxia or difficulty in smooth visual pursuits and jerkiness in gaze tracking. M:F, 2:1. renal disease seen in those with retinal involvement. rarely hepatic fibrosis., AR inheritance

Back 1083

Joubert syndrome

Front 1084

distinctive facial features (arched eyebrows, long eyelashes, long palpebral fissues with lower lids everted, flat broad tip of nose, large earlobes), DD, ID mild to severe, seizures, microcephaly, hypotonia, nystagmus, strabismus, short stature, scoliosis, short 5th fingers, problems with hip/knee joints, cleft palate, dental problems, fetal finger pads, heart abnormalities, otitis media, HL, early puberty, MLL2 mutation, AD

Back 1084

Kabuki syndrome

Front 1085

MLL2 associated with what condition?

Back 1085

Kabuki

Front 1086

renal cystic dysplasias (95-100%), large polycystic kidneys, CNS malformations (encephalocele (60-80%), post-axial polydactyly, hepatic development defects/fibrosis, limb bowing, limb shortening, clefting, other CNS malformations, pulmonary hypoplasia, MKS1-6 mutations, AR inheritance

Back 1086

Meckel-Gruber syndrome

Front 1087

MKS1-6 associated with what condition?

Back 1087

Meckel-Gruber

Front 1088

LIS1 gene associated with what condition?

Back 1088

Miller-Dieker syndrome

Front 1089

hypotonia, DD, growth retardation, obesity, microcephaly, orofacial clefting, typical facial features (frontal bossing, small and pointed chin, flat nose, low-set small ears, deep set eyes, thickened ear helices, midface hypoplasia, small mouth with down-turned corners, short/narrow and slating palpebral fissues, orofacial clefting). Minor cardiac malformations, CM, seizures, ventricular dilation, SNHL, usually maternally derived

Back 1089

monosomy 1p36

Front 1090

underdevelopment or absence of pectoralis muscles on one side of the body and webbing of fingers (cutaneous syndactyly) of hand on same side (ipsilateral). Usually on R side of body and more in males than females (3:1). Can also have abnormal GI tract, brachydactyly, dextrocardia, diaphragmatic hernia, absent humerus, biliary tract anomalies, maternal DM, oligodactyly, radius absent, rhizomelic micromelia, ulna absent, upper limb asymmetry, abnormal rib, simian crease on affected side, hypoplasic absent nipples, scapula anomaly, kidney anomaly, encephalocele, microcephaly, ureter anomalies, vertebral anomaly, etc. Rarely NHL, leukemia. some can be associated with Mobius syndrome and Klippel-Fiel Syndrome. caused by interruption of embryonic blood supply to arteries lying under collarbone

Back 1090

Poland Syndrome/Sequence

Front 1091

congenital bilateral facial paralysis with inability to abduct eyes

Back 1091

Mobius syndrome

Front 1092

IUGR, MR, heart, kidney, genital defects, limb malformations (upper limb>lower), craniofacial (CL/P, premaxillary protrusion, micrognathia, microbrachycephaly, malar hypoplasia), facies: downturned palpebral fissures, hypertelorism, exophthalmos, corneal clouding, beaked nose, ear malformations, sparse silvery-blond hair. mildly affected may live into adulthood, ESCO2 mutation, AR inheritance

Back 1092

Roberts Syndrome

Front 1093

ESCO2 associated with what condition?

Back 1093

Roberts Syndrome

Front 1094

inheritance of Roberts Syndrome

Back 1094

AR

Front 1095

distinctive craniofacial features (macrocephaly, broad prominent forehead, low-set ears, ocular hypertelorism, prominent eyes, midface hypoplasia, short upturned nose with depressed nasal bridge and flared nostrils, large and triangular mouth with exposed incisors and upper gums, gum hypetrophy, misaligned teeth, ankyloglossia, micrognathia), skeletal abnormalities (short stature, mesomelic or acromesomelic limb shortening, hemivertabrae with fusion of thoracic vertebrae, brachydactyly). Also: micropenis, reduced clitoral size and hypoplasia of labia majora, renal tract anomalies, nail hypoplasia, dystrophy, seen most in Omani and Turk consanguinous couples, AR, ROR2 mutation

Back 1095

Robinow sequence

Front 1096

ROR2 associated with what condition?

Back 1096

Robinow Sequence

Front 1097

mild-mod infantile hypotonia, feeding problems and FTT, short stature, brachydactyly, opthalmologic and ORL abnormalities, early speech delay w/without heating loss, peripheral neuropathy, sleep problems, stereotypic maladaptive behaviors (self-injurious, inattention, hyperactivity, impulsivity, disobedience, self-hug and lick and flip page turning motion, mild-mod MR, coarsening face over time, synophrys, RAI1 mutation, AD inheritance

Back 1097

Smith-Magenis Syndrome

Front 1098

RAI1 mutation associated with what condition?

Back 1098

SMith-Magenis Syndrome

Front 1099

inheritance of Smith-Magenis Syndrome

Back 1099

AD

Front 1100

absence of radius in both forearm, deficiency of platelets (thrombocytopenia) in infancy and becomes more severe; easy bruising and frequent nosebleeds, hemorrhages in brain and other organs (esp. in 1st year of life), DO have thumbs, unusual facial features (micrognathia, prominent forehead, low-set ears), 50% have allergic reaction to cow's milk, RBM8A mutation, AR inheritance

Back 1100

Thrombocytopenia-absent radius syndrome (TAR)

Front 1101

RBM8A mutation associated with what condition?

Back 1101

TAR syndrome

Front 1102

inheritance of TAR syndrome?

Back 1102

AR

Front 1103

Vertebral anomalies, Anal atresia, Cardiac malformations (VSD< PDA, TOF, TOV), Tracheoesophageal fistula, Esophagela atresia, Renal anomalies, Limb anomalies (polydactyly, humeral hypoplasia, radial aplasia, proximally placed thumb). Diagnosis requires 3/7 features. may have hydrocephalus as a variant, usually isolated

Back 1103

VATER/VACTERL association

Front 1104

What does WAGR stand for?

Back 1104

Wilms tumor (30-60%), aniridia, genital anomalies (cryptorchidism, streak ovaries, bicornate uterus, hypospadias, ambiguous genitalia), MR (70%), epilepsy, obesity common, renal failure, proteinuria, asthma, infections, apnea, dental malocclusion, ADHD, autism, scoliosis/kyphosis, pancreatiti

Front 1105

WT1 and PAX6 associated with what condition?

Back 1105

WAGR

Front 1106

inheritance of WAGR?

Back 1106

AD

Front 1107

"greek warrior helmet appearance", microcephaly, prea and postnatal growth deficiency, MR of variable degree, seizures, facial asymmetry, ptosis, igA deficiency, structural brain abnormalities, CL/P, CHD (ASD>PVS>VSD>PDA>AI>TOF), renal U/S, 4p del, most de novo

Back 1107

Wolf-Hirschorn syndrome

Front 1108

4p deletion leads to what condition?

Back 1108

Wolf-Hirschorn Syndrome

Front 1109

port-wine stain and varicosities of extremity associated with hypertrophy of affected limb's bony and soft tissue, caused by intrauterine damage to sympathetic ganglia or intermediolateral tract leading to dilated microscopic A/V anastamoses, AGGF1 and KTS mutations

Back 1109

Klippel-Trenaunay-Weber Syndrome

Front 1110

What does BPES stand for?

Back 1110

blepharophimosis, ptosis, epicanthus inversus, and telecanthus. BPES type 1: includes above features and POF. Type 2: only 4 major features and also lacrimal duct anomalies, amblyopia, strabismus, refractive errors. Minor features: broad nasal bridge, low-set ears, short philtrum

Front 1111

FOXL2 mutation associated with what condition?

Back 1111

BPES

Front 1112

inheritance of BPES?

Back 1112

AD

Front 1113

blurred or clouded vision progressing to degeneration of retinal nerve and then optic atrophy. Fundus: vascular tortuosity of central retinal vessels, circumpapillary telangiectatic macroangiopathy, swelling of retinal nerve fibers, MTND1,4,5,6 mutations, mitochondrial

Back 1113

Leber Hereditary Optic Neuropathy

Front 1114

dense congenital cataracts in all, infantile glaucoma in 50%, all have impaired vision, hypotonia, absent DTR's, motor delay, MR, proximal renal tubular dysfunction, glomerulosclerosis resulting in slowly progressive renal failure, ESRD after 10-20yo, OCRL gene mutation, X-linked

Back 1114

Lowe Syndrome

Front 1115

INheritance of Lowe Syndrome

Back 1115

X-linked

Front 1116

OCRL associated with what condition?

Back 1116

Lowe Syndrome

Front 1117

leukocoria, strabismus, visual deterioration, conjunctivitis; unilateral (70%) or bilateral (30%) retinoblastoma; risk of secondary neoplasms d/t radiotherapy treatment (osteosarcomas, soft tissue sarcomas, melanomas), many inheritance patterns

Back 1117

Retinoblastoma

Front 1118

Type I: congenital profound HL, congenital balance problems, RP onset pre-puberty. Type II: congenital mild-severe HL, normal balance, RP onset teens-20's. Type III: progressive later onset HL, progressive balance problems, variable onset RP, 11 genes, AR inheritance

Back 1118

Usher Syndrome

Front 1119

inheritance of Usher Syndrome

Back 1119

AR