Genetics, Anomalies And Syndromes

Front 1

How often do infants with esophageal atresia have VACTERL association?

Back 1

One third of the time.

Front 2

What condition in a neonate presents in a mother with polyhydramnios with frequent need of oropharyngeal suctioning and displays cyanosis when suctioned, pulse ox from 94% to 70% with cyanotic episodes, rales on auscultation, normal heart sounds with no murmurs and no abdominal distention?

Back 2

Tracheoesophageal fistula

Hint 2

The intermittent cyanosis exhibited by the newborn may be due to pooling of oral secretions in the hypopharynx, airway obstruction, aspiration of oral secretions through the larynx into the trachea (because the infant cannot swallow these secretions), pneumonitis, or hypoxia resulting from the reflux of gastric contents via the TEF into the tracheobronchial tree. The maternal history of polyhydramnios is a clue to likely swallowing dysfunction or gastrointestinal tract obstruction. The physical examination and judicious use of diagnostic imaging tools such as plain films and ultrasonography to assess for the presence of vertebral anomalies, anorectal stenosis or atresia, structural heart disease, renal anomalies, and limb anomalies is important in determining if the esophageal atresia or TEF are isolated defects or part of the VACTERL association, which occurs in one third of infants who have esophageal atresia.

TEF and esophageal atresia is a surgical emergency that requires early evaluation for surgical ligation of the TEF to protect the airway. Until surgery is performed, vigilant oropharyngeal suctioning is required, and the newborn's head should be kept elevated. Some newborns may require tracheal intubation and assisted ventilation. Early insertion of a gastrostomy tube for gastrointestinal decompression and subsequent feeding until such time as the esophagus can be used also is common. Surgical anastomosis of the proximal and distal esophagus may be accomplished as a later procedure.

Measuring bedside glucose concentration is important in newborns who have respiratory distress but should follow evaluation of airway obstruction in the newborn in the vignette. Echocardiography can help in the evaluation of the newborn for structural heart disease, but the documented normal room air saturation of 94% indicates no fixed cardiac shunt or cyanotic lesion, making this test less imperative at this time. Renal ultrasonography is indicated if VACTERL association is suspected but requires an initial diagnosis of TEF. An umbilical arterial catheter may or may not be indicated, depending on the degree of respiratory distress.

Front 3

Port wine stains are associated with what syndrome?

Back 3

Sturge-Weber syndrome

Front 4

What syndrome is associated with seizures and meningeal and cerebral cortex abnormalities ipsilateral to the port wine stain and the presence of a port wine stain in the V1 region. Eye involvement, also occurs in 60% of patients.

Back 4

Sturge-Weber syndrome

Front 5

What is the most common eye involvement in Sturge-Weber Syndrome?

Back 5

Glaucoma

Front 6

What syndrome is characterized by a large atypical-appearing hemangioma that actually is a hemangioendothelioma or tufted angioma.

Back 6

Kasabach-Merritt Syndrome

Front 7

What are the characteristic skin findings in neurofibromatosis type 1?

Back 7

cafe au lait macules which may be present at birth and neurofibromas which typically appear during childhood or early adolescence.

Front 8

What is characterized by recurrent epistaxis and cutaneous telangiectases that develop later in life?

Back 8

Osler-Weber-Rendu disease AKA hereditary hemorrhagic telangiectasia

Front 9

What has the characteristic skin findings of hypopigmented macules, adenoma sebaceum, periungual fibromas among others?

Back 9

Tuberous Sclerosis - also has facial plaques and shagreen patches.

Front 10

How are port wine stains treated and which lesions have the best response?

Back 10

Pulsed dye laser. Lesions in the periorbital area and central forehead generally respond better than do lesions in the midface or on the limbs.

Hint 10

PWSs can be treated effectively with pulsed dye laser. Laser treatment may result in complete resolution or significant lightening of the lesion, and the degree of effectiveness is related to the location of the lesion (Item C35D). Results of studies are conflicting, but lesions in the periorbital area and central forehead generally respond better than do lesions in the midface or on the limbs. Other factors associated with improved results include lesion size less than 20 cm and age at onset of therapy. Risks of treatment are small and include atrophy, hypertrophy, and hyperpigmentation of the treated area. PWSs recur in many patients after treatment.

Front 11

What genetic anomaly have features of punched-out scalp lesions, bilateral cleft lip and palate, polydactyly, holoprosencephaly, microcephaly and cardiac defects?

Back 11

Trisomy 13

Hint 11

Trisomy 13 The newborn described in the vignette has a 47,XX+13 karyotype consistent with trisomy 13. Her unusual features of "punched-out" scalp lesions (also known as "aplasia cutis"), bilateral cleft lip and palate, and polydactyly are present in at least 50% of newborns who have this diagnosis. Other common anomalies in affected individuals include holoprosencephaly (incomplete septation of the frontal lobes), microcephaly, and cardiac defects (80%).

Front 12

What congenital anomaly presents with webbed neck with low posterior hairline, broad chest with widely spaced nipples, narrow and hyperconvex nails, and cardiac defects, most commonly bicuspid aortic valve?

Back 12

Turner syndrome

Hint 12

Approximately 50% of individuals who have Turner syndrome have a 45,X karyotype; the remainder have a mosaic karyotype that includes a cell line consistent with Turner syndrome, such as 45,X/47,XXX, or a karyotype with 46 chromosomes wherein one of the X chromosomes is aberrant (eg, ring X, isochromosome Xq). Affected newborns may exhibit dysmorphisms or may appear completely normal. Unusual features include webbed neck with low posterior hairline, broad chest with widely spaced nipples, narrow and hyperconvex nails, and cardiac defects, most commonly bicuspid aortic valve.

Front 13

What congenital anomaly has features including IUGR, prominent occuput, small facial features, clenched hands with overlappy fingers and hypertonia?

Back 13

Trisomy 18

Hint 13

Individuals who have trisomy 18 usually have a 47,XX(or XY)+18 chromosome complement. Characteristic features include intrauterine growth restriction, prominent occiput, small facial features, clenched hands with overlapping of the second finger over the third and the fifth finger over the fourth, and hypertonia. Trisomy 18 has a poor prognosis; approximately 50% of affected individuals die by 2 weeks of age and 90% die by 1 year.

Front 14

What congenital anomaly is characterized by midface hypoplasia with epicanthal folds, upslannting palpebral fissures, small ears with overfolded pinnae, redundant nuchal skin and hypotonia?

Back 14

Trisomy 21

Hint 14

47,XX(or XY)+21 is the most common karyotype seen in individuals who have Down syndrome. Affected newborns typically exhibit midface hypoplasia with epicanthal folds, upslanting palpebral fissures, small ears with overfolded pinnae, redundant nuchal skin, and hypotonia. Many affected individuals have fifth finger clinodactyly (in-curving) (Item C39), and almost 50% have a single transverse palmar crease. Approximately 45% of affected individuals have congenital heart defects.

Front 15

What percentage of infants with Trisomy 21 have congenital heart defects?

Back 15

45%

Front 16

How is the diagnosis of PCOS made?

Back 16

The diagnosis of PCOS, using the 2003 Rotterdam criteria, requires, in addition to exclusion of related conditions, the presence of two of the following three criteria: 1) oligo- or anovulation, 2) clinical or biochemical signs of hyperandrogenism, and 3) polycystic ovaries. Oligo- or anovulation presents as irregular menses, and hyperandrogenism may present as acne, increased body hair, and rarely, clitorimegaly (a transverse clitoral diameter greater than 3 mm).

Front 17

How often is deafness inherited? and what type of inheritance?

Back 17

~50% of cases
-80% AR
-18% AD
-2% X-linked recessive

Front 18

What syndromes are common causes of deafness?

Back 18

ADUCT
Alport, Down, Usher, Crouzon, Treacher-Collins

Front 19

What is the term that refers to a pattern of anomalies that results from a single identifiable event in development?

Back 19

Sequence

Front 20

What can present with disruptive clefts of the face and palate, constriction rings of the limbs and/or digits and amputations?

Back 20

Amniotic Band Sequence

Front 21

What is the most common craniofacial malformation?

Back 21

cleft lip/palate

Front 22

What is the second most common craniofacial malformation?

Back 22

Hemifacial Microsomia

Front 23

What is the association of external ear anomalies llike microtia - smallness of the auricle of the ear with a blind or absent external auditory meatus, anotia, canal atresia, preauricular tags, with maxillary/mandibular hypoplasia?

Back 23

Hemifacial Microsomia

Front 24

What other anomalies commonly occur with hemifacial microsomia?

Back 24

Cervical vertebral anomalies (33%), Cardiac anomalies, and Renal anomalies.

Front 25

What syndrome presents with hemifacial microsomia, epibulbar lipodermoids, vertebral defects, cardiac anomalies, renal anomalies and sometime conductive hearing loss?

Back 25

Goldenhar Syndrome

Front 26

How does the term Goldenhar Syndrome differ from Hemifacial Microsomia?

Back 26

They are considered to be the same disorder, but Goldenhar syndrome is ONLY used if epibulbar dermoids are present.

Front 27

What syndrome presents with branchial cleft fistulas or cysts, preauricular pits, cochlear and tapes malformation, mixed sensory and conductive hearing loss and renal dysplasia/aplasia? (and occasional pulmonary hypoplasia)

Back 27

Branchio-Oto-Renal Syndrome

Front 28

What form of inheritance does Branchio-Oto-Renal (BOR) Syndrome follow?

Back 28

Autosomal Dominance

Front 29

What type of inheritance do ataxia-telangiectasia, Bloom syndrome, Fanconi syndrome and xeroderma pigmentosum share?

Back 29

Chromosomal Instability Syndromes

Front 30

What races have the highest and lowest rates of cleft lip and/or cleft palate?

Back 30

Highest is Native Americans
Lowest are African Americans

Front 31

What is the incidence of cleft lip and/or palate?

Back 31

1/250 to 1/3000 depending on culture and race

Front 32

What is characterized by:
-mandibular hypoplasia
-glossoptosis
-micrognathia
-respiratory distress
-feeding problems
-cleft palate
-interrupted closure of the lateral palantine ridges

Back 32

Pierre-Robin Sequence

Front 33

What syndrome presents with
-mandibular and maxillary hypoplasia
-zygomatic arch clefts
-ear malformations
-down-sloping palpebral fissures
-colobomata of the lower eyelids
-conductive hearing loss

Back 33

Treacher-Collins Syndrome
(Mandibulofacial Dysostosis Type 1)

Front 34

How is Treacher-Collins Syndrome inherited

Back 34

Autosomal Dominance

Front 35

How common is craniosynostosis and how often is it inherited?

Back 35

Sporadically in 1/2000 live births and 1/25,000 cases are hereditary.

Front 36

What is the most common suture involved in craniosynostosis and what follows?

Back 36

Sagittal > Coronal > Metopic > Lamboid

Front 37

What is the term for a cone shaped head caused by early fusion of coronal, sphenofrontal and frontoethmoidal sutures?

Back 37

Turricephaly

Front 38

What is the term for a head shape that is characterized by a keel-shaped forehead and hypotelorism caused by early fusion of metopic sutures?

Back 38

Trigonocephaly

Front 39

What is the term for a head shape with unilateral flattening of the forehead, elevation of the ipsilateral orbit and eyebrow and a prominent ear on the affected side resulting from early fusion of coronal and sphenofrontal sutures?

Back 39

Frontal plagiocephaly

Front 40

What is the term for a long narrow head shape with frontal and occipital prominence resulting from early fusion of sagittal sutures?

Back 40

Scaphocephaly

Front 41

Craniosynostosis is more common in which sex? What is the exception?

Back 41

Males predominate 5:1 but frontal plagiocephal (coronal & sphenofrontal sutures) is more common in girls.

Front 42

What other feature, aside from the head, help distinguish between the different genetic syndroms with craniosynostosis?

Back 42

Particular Hand Malformations

Front 43

How can you differentiate between plagiocephaly and lamboid synostosis?

Back 43

Lamboid synostosis shows sclerosis of the
Lamboid suture on physical exam and head CT.
Lambdiod is RARE
Plagiocephaly is COMMON

Front 44

What is the term for positional flattening of the head caused by positional preference?

Back 44

Plagiocephaly

Front 45

What presents as postnatal head malformation with:
-torticollis
-ipsilateral frontal prominence
-anterior displacement of ipsitalteral ear
-absent contralateral occipitoparietal prominence
-no lambdoid ridge or sub-mastoid prominence
-and stops progressing after seven months of age?

Back 45

Plagiocephaly

Front 46

What is the most common skeletal dysplasia and how often does it occur?

Back 46

Achondroplasia
1/20,000 live births

Front 47

What is characterized by:
-disproportionately short stature -rhizomelic shortening -trident hands -macrocephaly -flat nasal bridge -prominent forehead - midface hypoplasia

Back 47

Achondroplasia

Front 48

What is rhizomelic shortening? What is it associated with?

Back 48

Short lengths of the most proximal segment of upper arms and legs compared to distal segments which is seen in achondroplasia

Front 49

What form of inheritance does achondroplasia have?

Back 49

Autosomal Dominant with most having de novo mutation of FGFR3 (fibroplast growth factor receptor 3) on chromosome 4p16.3

Front 50

What congenital anomaly occurs due to mutation on 4p16.3?

Back 50

Achondroplasia

Front 51

What phenotypic presentation usually presents in achondroplasia?

Back 51

Children with achondroplasia usually do not have other malformations

Front 52

What is the term referring to hands that are short with fingers that are broad and has digits 3 and 4 splayed more distally than proximally?

Back 52

Trident hands (seen in achondroplasia)

Front 53

What are children with achondroplasia at increased risk for?

Back 53

-serous otitis media
-motor milestone delay
-bowing of the legs
-orthodontic problems
-foramen magnum stenosis
-craniocervical junction abnormalities

Front 54

What can foramen magnum stenosis and/or craniocervical junction abnormalities lead to in infants with achondroplasia?

Back 54

Compression of upper spinal cord resulting in apnea, quadriparesis, growth delay and hydrocephalus.

Front 55

What additional vital/measurements are recommended by the AAP
in caring for infants with achondroplasia?

Back 55

Measuring size and shape of the fontanelle
and monthly monitoring of the occipitofrontal circumference

Front 56

What is known to increase the risk of mutation for achondroplasia? (de novo mutations)

Back 56

Advanced PATERNAL Age

Front 57

What are the minor manifestations of Marfan Syndrome?

Back 57

Skeletal (moderate pectus excavatum, joint hypermobility, high arched palate)
Ocular (abnormally flat cornea, hypoplastic iris or cilliary muscle)
Cardiac (MVP, dilation of the main pulmonary artery)
Pulmonary (spontaneous pneumothorax apical blebs)
Skin (striae atrophicae, recurrent or incisional hernias)

Front 58

What is characterized by:
-hypermobile joints
-dystrophic scarring
-hyperexxtensible skin
-easy bruising
-abnormal skin texture (wet chamois)
-skin is also very fragile with skiny thin scarring, gaping "fish-mouth" appearance at the tear

Back 58

Ehlers-Danlos Syndromes

Front 59

What screenings should be done in patients with Ehlers Danlos Syndromes?

Back 59

ECHO, CT or MRI due to high incidence of MVP and proximal aortic dilatation

Front 60

What is treatment of Ehlers Danlos aimed at?

Back 60

Prevention of trauma - shin guards, high boots, knee pads etc and NO CONTACT SPORTS

Front 61

How are Thanatophoric Dysplasias inherited?

Back 61

Autosomal Dominant and almost always due to denovo mutations

Front 62

What is the most common presentation of thanatophoric dysplasias (type 1 and 2)

Back 62

Death either from compression of the cervicomedullary region of the foramen magnum or to pulmonary hypoplasia. They have macrocephaly and very short limbs.

Front 63

What causes death in infants/fetus' with
thanatophoric dysplasias?

Back 63

Death is due to compression of the cervicomedullary region
of the foramen magnum or to pulmonary hypoplasia

Front 64

What type of skull shape is characteristic of thanotophoric dysplasia type 2?

Back 64

Cloverleaf skulls

Front 65

What are the differences between thanatophoric dysplasia type 1 and type 2?

Back 65

Type 1 - bowed femurs

Type 2 - straight femurs and cloverleaf skull

Front 66

What refers to a disorder characterized by
-osseus fragility
-short stature
-skeletal anomalies
-autosomal dominant inheritance
NO RETINAL HEMORRHAGE OR SUBDURAL HEMATOMAS

Back 66

Osteogenesis Imperfecta

Front 67

What type of osteogenesis imperfecta is also known as "brittle bone disease"?

Back 67

Type 1

Front 68

Which is the most common form of osteogenesis imperfecta?

Back 68

Type 1

Front 69

Which is the most severe type of osteogenesis imperfecta?

Back 69

Type 2

Front 70

What are the characteristic xray findings that confirm the diagnosis of achondroplasia?

Back 70

1- squared off iliac wings
2- flat and irregular acetabulum roofs
3- thick femoral necks
4- ice-cream-scoop" shaped femoral heads
5- rhizoelic shortening

Front 71

Which are more comon disorders autosomal recessive or autosomal dominant?

Back 71

Autosomal Dominant

Front 72

How do you calculate the probabilities or population frequencies of various diseases?

Back 72

Incidence x Carrier frequency (F) x Carrier frequency (M)

Front 73

What is the incidence of cystic fibrosis and how is it inherited?

Back 73

Incidence is 1/1600
Inheritance is Autosomal Recessive

Front 74

What type of inheritance causes Hemophilia A?

Back 74

X - linked

Front 75

What presents with progressive muscle weakness, calf hypertrophy, cardiomegaly, cognitive delays and gower sign?

Back 75

Duchenne Muscular Dystrophy

Front 76

What percentage of males with an x-linked recessive allele for a disease will be affected?

Back 76

100%

Front 77

What is it called when females have two populations of cells from their x chromosomes?

Back 77

Soatic mosaicism

Front 78

What type of inheritance has only females that transmit disease, can appear to "skip" a generation, have daughters that are obligate carriers and transmit to 50% of sons.

Back 78

X - linked recessive

Front 79

What presents with severe hypotonia, obesity, small hands and feet and mental retardation?

Back 79

Prader-Willi

Front 80

What presents with normal appearance at birth with development by 6-12 mos of age of seizures, mental retardation, icrocephaly, ataxia, hand-flapping and an abnormal gait?

Back 80

Angelman Syndrome

Front 81

What results from deletion of all maternally active genes from a portion of chromosome 15?

Back 81

Angelman Syndrome

Front 82

What results from deletion of all paternally active genes from a portion of chromosome 15?

Back 82

Prader-Willi Syndrome

Front 83

What accounts for 70% of cases of Prader-Willi and Angelman Syndromes?

Back 83

Genomic Imprinting

Front 84

What type of inheritance occurs if both coppies of a chrosome are from only one parent?

Back 84

Uniparental Disomy

Front 85

What results from uniparental diisomy where a child receives both copies of maternal chromosome 15?

Back 85

It lacks a paternal copy so it has Prader-Willi

Front 86

What causes 22q11.2-
(DiGeorge Syndrome)?

Back 86

Developmental defect of derivatives of the 3rd and 4th pharyngeal pouches associated with agenesis or hypoplasia of the thymus and parathyroid gland, heart defects and branchial arch defects.

Front 87

What is the incidence of abnormalities of X or Y chromosomes in a neonate?

Back 87

1/500

Front 88

How common is Turner Syndrome?

Back 88

1/2500-1/5000 neonate females

Front 89

What is the most common chromosomal anomaly involving the sex chromosomes?

Back 89

Klinefelter Syndrome
47 XXY

Front 90

What syndrome is characterized by
- small testes
- gynecomastia
- delayed secondary sex development
- tall stature
- azoospermia
- infertility

Back 90

Klinefelter Syndrome
46 XXY

Front 91

How doo 47 XYY males present?

Back 91

They are taller than average but no other difference than the general population

Front 92

What affect do increased X chromosomes on the clinical presentation of a person?

Back 92

The more X chromosomes there are, the higher the degree of phenotypic abnormalities and worse neurologic problems

Front 93

What syndrome is characterized by

-posteriorly rotated ears
-short stature
-ovarian failure/gonadal dysgenesis
-lack of secondary sexual characteristics
-increased risk for gonadoblastoma
-cardiovascular anomalies
-fetal cystic hygroma
-lymphedemal of hands/feet
-cubitus valgus

Back 93

Turner (45 XO)

Front 94

What are the comon cardiac anoalies associated with Turner Syndrome?

Back 94

Bicuspid Aortic Valves
Coarctation of the Aorta (15-20%)

Front 95

What percent of fetuses with Turner Syndrome Spontaneously abort?

Back 95

99%

Front 96

What chromosomal anomaly is characterized by
-cleft palate, velopharyngeal incompetence
-thymus agesesis or hypoplasia
-immune deficiencies
-parathyroid gland hypoplasia/agenesis
-hypocalcemia
-hypoplasia of the auricle and external auditory canal
-cardiac abnormalities (TOF>interrupted aortic arch>VSD>truncus arteriosus)
-short stature & behavioral problems

Back 96

22q11.2-
VCF or DiGeorge Syndrome

Front 97

What cardiac anomalies occur in DiGeorge Syndrome (22q11.2-) and which is more common?

Back 97

Tetrology of Fallot
then
Interrupted Aortic Arch
then
VSD
then
Truncus Arteriosus

Front 98

What results ffrom uniparental disomy where a child receives both copies of paternal chromosome 15?

Back 98

It lacks a maternal copy so it has Angelman Syndrome.

Front 99

What type of inheritance
-occurs in more than one sibling
-affects males and females equally
-males and females can each transmit the altered allele
-the risk for 2 heterozygotes to have an affected child is 1/4
-consanguinity increases the risk of having offspring with the disorder

Back 99

Autosomal Recessive

Front 100

What syndromes are caused by 22q11.2- (deletion)?

Back 100

1-DiGeorge Syndrome
2-Shprintzen Syndrome
3-Velocardiofacial (VCF)Syndrome
4-CATCH 22 (Cleft palate, Absent Thymus, Congenital Heart Disease)

Front 101

What disorders are commonly associated with Turner Syndrome in childhood or adulthood?

Back 101

Hashimoto thyroiditis
Alopecia
Carbohydrate intolerance
Vitiligo
GI Disorders

Front 102

If a woman had pyloric stenosis as a child are her boys or her girls more likely to be affected?

Back 102

males/boys

Front 103

How often does pyloric stenosis occur in males?

Back 103

1/300 males

Front 104

How often does pyloric stenosis occur in females?

Back 104

1/1,200 females

Front 105

Whose children are more likely to be affected by pyloric stenosis, the affected father or the affected mother?

Back 105

The mother

Front 106

If the recurrence risk increases with subsequent children who are affected by the disorder, what type of inheritance is involved?

Back 106

Multifactorial

Front 107

How does the recurrence risk change in multifactorial inheritance if the affected individual is a member of the less comonly affected sex?

Back 107

It increases

Front 108

Which sex is more commonly affected by infantile autism and by how much?

Back 108

Males are four times more likely to be affected than girls

Front 109

What factors increase recurrence risk in multifactorial inheritance? What makes it decrease?

Back 109

Increase in number of affected individuals increases in family

Increase if the affected individual is of less comonly affected sex

Increase if affected individual has a more severe form/case

Decrease as the degree of relationship to the affected individual decreases (more distant relative)

Front 110

How is recurrence risk associated with prevalence in the general population in multifactoral inheritance?

Back 110

Multifactorial: recurrence riskcorrelates with the prevalence in the general population

Front 111

How is recurrence risk associated with prevalence in the general population in single gene disorders?

Back 111

Single gene disorders: the recurrence risk is independent of the general population

Front 112

What has folic acid supplementation been proven to do prior to and through early pregnancy? What else is it thought to do?

Back 112

proven to prevent neural tube defects and possibly reduce the risk of other birth defects

Front 113

How much DNA/genes do monozygotic twins share?

Back 113

100%

Front 114

How much DNA/genes do dizygotic twins share?

Back 114

50%

Front 115

How is concordance differ between monozygotic and dizygotic twins in
-autism
-cleft lip/palate
-clubfoot
-spina bifida

Back 115

M vs D
Autism 60% 0%
Clefts 38% 8%
Clubfoot 32% 3%
Spina Bifida 72% 33%

Front 116

What are the indications for chromosomal analysis?

Back 116

Multiple birth defects
MR/DD
Growth abnormalities
Abnormal sexual development
Recurrent miscarriiages

Front 117

How common is Trisomy 21? How is the incidence preterm different than the incidence at birth?

Back 117

1/800 live births
Incidence in conceptions is more than 2x the incidence at birth

Front 118

What percent of those with Down Syndrome have 3 copies of the whole chromosome 21?

Back 118

94%
3% have only part of #21
3% are mosaics

Front 119

What chromosomes are commonly involved in translocations when a child with Down's has only part of the longarm of chromosome 21?

Back 119

Chromosomes 14, 15 or 13

Front 120

What is the ONLY factor shown to increase the risk of having a child with Down Syndrome?

Back 120

Advanced/Increasing Maternal Age

Front 121

Screening in women under the age of 35 can include looking for an abnormal maternal serum screen study consistent of what?

Back 121

-low maternal serum AFP
-low unconjugated estriol
-elevated HCG
-elevated inhibin levels

Front 122

What are the most commonly found phenotypical patterns in Down Syndrome?

Back 122

Hypotonia
Small Ears
Mental Retardation

Front 123

What phenotypic patterns are MOST SPECIFIC to Down Syndrome?

Back 123

Brachydactyly
Absent to very small nipple buds
Central placement of the posterior hair whorl

Front 124

What is it called when a child has short, broad fingers and toes, especially with broad space between 1st and 2nd toes?

Back 124

Brachydactyly

Front 125

What are speckled irises called?

Back 125

Brushfield spots

Front 126

What features are common in Down Syndrom but NONSPECIFIC

Back 126

-microcephaly
-upslanted palpebral fissures
-flat midface
-full cheeks
-epicanthal folds
-single transverse crease
-speckled irises
-high arched palate
-hypoplasia of the middle phalanx of 5th finger

Front 127

What heart defects are common in Down Syndrome and how common are they?

Back 127

50% of Down's Patients have heart defects
1/3 have AV canal defects
1/3 have VSDs
1/3 have ASD 2nd & TOF

Front 128

When do you get an ECHO for a child with Down's or suspected Down's?

Back 128

ALWAYS - ECHO is mandatory for all children/infants with Down's or suspected Downs.

Front 129

What GI defects are most common in infants with Down Syndrome? How common are they?

Back 129

5% have duodenal atresia or Hirschsprung disease

Front 130

How common are occular problems in children with Down's, and what types of defects occur?

Back 130

Eye problems are very common
- strabismus
- refractive errors
- congenital cataracts (5%)

Front 131

What is the mean IQ of children with Down Syndrome?

Back 131

20-50

Front 132

How are infantile spasms treated?

Back 132

Vigabatrin

Front 133

What percent of infants with tuberous sclerosis have cardiac rhabdomyomas?

Back 133

50%

Front 134

What Syndrome is characterized by:
-cancer and benign tumors of eyes, CNS, kidneys, pancreas, adrenal glands and reproductive glands
-is caused by a mutation on chromosome 3
-most classically presents as a cerebellar hemangioblastoma in adolescence or retinal angioma by 10 years of age?

Back 134

Von-Hippel-Lindau (VHL) Syndrome

Front 135

What is the classic presentation of Von Hippel-Lindau Syndrome?

Back 135

Cerebellar hemangioblastoma in adolescence
OR
Retinal angioma by 10 years of age

Front 136

What is the leading cause of mortality of Von Hippel-Lindau Syndrome (VHL)?

Back 136

Renal cell carcinoma (presents in the 40s and occurs in nearly 40% of patients)

Front 137

How is Von Hippel Lindau Syndrome diagnosed?

Back 137

2 or more hemangioblastomas in the CNS or retina
or
Finding 1 single hemangioblastoma with 1 of: pheochromocytoma, endolymphatic sac tumors, cysts in the kidney/pancreas, renal cell carcinoma or pancreas involvement, neuroendocrine tumors
OR
Having a 1st degree relative and any 1 of above

Front 138

What syndrome includes
- Cowden syndrome
- Bannayan-Riley-Ruvalcaba Syndrome
- Proteus Syndrome
- Proteus-like syndrome

Back 138

PTEN harmartoma tumor syndrome (PHTS)

Front 139

What syndrome is a multiple hamartoma syndrome with a high risk of benign and malignant tumors of thyroid, breast and endometrium?

Back 139

Cowden Syndrome

Front 140

What is Nikolsky sign?

Back 140

When minimal friction applied to the skin results in the removal of the superficial layer of epidermis.

Front 141

What is the genetic definition that refers to two different alleles at a locus on a pair of homologous chromosomes?

Back 141

Heterozygous

Front 142

What type of inheritance does Marfan syndrome have?

Back 142

Marfans has pleotropic effects.

Front 143

What is the genetic definition that refers to genes that produce many effects?

Back 143

Pleotropic

Front 144

What type of inheritance does Treacher-Collins Syndrome have?

Back 144

Autosomal dominant with variable expressivity.

Front 145

10% of patients with retinoblastoma who have an autosomal dominant gene mutation causing retinoblastoma do not develop retinoblastoma. Why is that?

Back 145

Because retinoblastoma is autosomal dominant, but only has 90% penetrance.

Front 146

What genetic definition refers to reduced or incomplete genetic expression 100% of the time?

Back 146

Incomplete penetrance

Front 147

What genetic definition refers to the ability of a known disease-causing genotype to be expressed or the exhibit the disease phenotype?

Back 147

Penetrance

Front 148

What genetic definition refers to the observed expression (physical, biochemical and or physionlogical findings? of the genotype or gene mutation.

Back 148

Phenotype

Front 149

What genetic definition refers to the genetic constitution or different forms of a gene (alleles) at a given locus?

Back 149

Genotype

Front 150

What genetic definition refers to conditions that cluster in families and can include nongenetic as well as genetic conditions?

Back 150

Familial

Front 151

What genetic definition refers to conditions that can be transmitted from parent to offspring?

Back 151

Hereditary

Front 152

What genetic definition refers to a condition or anomaly present at birth?

Back 152

Congenital

Front 153

Familial refers to conditions that "cluster" in families and can include genetic and nongentic conditions. T or F?

Back 153

True

Front 154

All hereditary conditions are genetic so all genetic conditions are hereditary? T or F?

Back 154

False

Front 155

All hereditary conditions are familial but not all genetic conditions are familial. T or F?

Back 155

False

Front 156

What type of inheritance does retinoblastoma have?

Back 156

Autosomal dominance with 90% penetrance

Front 157

What genetic definition refers to individuals who have the same genetic condition (and sometimes even the exact genotype) but present with different phenotypes?

Back 157

Variable expressivity

Front 158

How often are children with severe mental retardation going to have cerebral dysgenesis on MRI?

Back 158

10-15%

Front 159

What syndrome is most often associated with bilateral closure of the coronal sutures?

Back 159

Courzon syndrome

Front 160

What syndrome involves premature closure of multiple sutures and syndactyly?

Back 160

Apert Syndrome

Front 161

What syndrome is associated with multiple fusions of cranial sutures, syndactyly, mental retardation, and possible congenital heart disease, orthopedic abnormalities and corneal opacities

Back 161

Carpenter Syndrome

Front 162

What IQ corresponds with mild mental retardation?

Back 162

50-75

Front 163

Mild mental retardation occurs how often?

Back 163

20-30/1000 or 2-3%

Front 164

Is mild mental retardation more common in boys or girls?

Back 164

boys

Front 165

How often is mild mental retardation associated with an identifiable chromosomal abnormality

Back 165

4-8%

Front 166

How often does servere mental retardation occur?

Back 166

1-4/1000

Front 167

Is mental retardation associated with socioeconomic factors?

Back 167

Mild MR is

Severe MR is NOT

Front 168

How often is severe mental retardation due to chromosomal abnormalities?

Back 168

30%

Front 169

What is the most common chromosomal abnormality that causes severe mental retardation?

Back 169

Down Syndrome.

Front 170

How often are CNS injuries responsible for severe mental retardation?

Back 170

15-20%

Front 171

What genetic definition refers to identical alleles at a particular gene locus.

Back 171

Homozygous

Front 172

What genetic definition refers to all chromosomes except the X or chromosome?

Back 172

Autosome

Front 173

What is the genetic definition when there are extra or misssing autosomes or sex chromosomes?

Back 173

aneuploidy

Front 174

What is the genetic term that refers to a structural birth defect or congenital malformations?

Back 174

Anomaly

Front 175

What is the genetic term for anomalies of several different structures that lie together in the same local body region during embryonic development?

Back 175

Complex

Front 176

What genetic definition refers to a recognizable pattern of structural defects, often with a predictable natural history that can be identified amongst several patients.

Back 176

Syndrome

Front 177

Is Pierre-Robin anomaly a
- complex
- phenotype
- syndrome or
- sequence

Back 177

sequence.

Front 178

What is the most common single gene abnormality that lead to clinical disorder?

Back 178

Autosomal Dominant

Front 179

Is Williams anomalies a
- complex
- phenotype
- syndrome or
- sequence

Back 179

A Syndrome

Front 180

Is Pena-Shokeir a
- complex
- phenotype
- syndrome or
- sequence

Back 180

Phenotype

Front 181

I "limb-body wall" anomaly a
- complex
- phenotype
- syndrome or
- sequence

Back 181

Complex

Front 182

What is the genetic definition that refers to a pattern of multiple anomalies that result from a single identifiable event in development?

Back 182

Sequence

Front 183

Is Cornelia de Lange a
- complex
- phenotype
- syndrome or
- sequence

Back 183

syndrome

Front 184

What percentage of a heterozygous parent with an autosomal dominant disorder passing the disorder to his/her child.

Back 184

50%

Front 185

What type of inheritance will have:
- disorders in one or more sibs, but not in other generations
- M & F equally affected
- M & F can each transmit the altered allele
- the risk for 2 heterozygotes to pass on is 1/4 (however they can all be affected or all NOT affected)
- Consanguinity increases the risk of having an offspring with this type of disorder

Back 185

Autosomal Recessive

Front 186

How do you calculate the probability or population frequencies of various diseases? IE) cystic fibrosis

CF 1/1600 = 1/20 x 1/20 x 1/4

Back 186

Frequency for carrier rate for each parent multiplied, then multiply by 1/4 because of autosomal recessive

Front 187

What type of inheritance will have:
- both sexes equally affected
- both sexes can transmit to kids
- no generation is skipped
- every affected person in family has a parent with the disorder (except de novo mutations)
- you will see father to son transmisssion.

Back 187

Autosomal Dominant

Front 188

What is the genetic transmission is neurofibromatosis Type I ?

Back 188

60% are denovo mutations which are then autosomal dominant.

Front 189

Marfan syndrome and achondroplasia have what risk factor in common?

Back 189

Advanced PATERNAL age

(as is true with most AD diseases)

Front 190

What should you suspect when a normal parent has more than one child affected with an autosomal dominant or X-linked condition?

Back 190

Germline mosaicism

Front 191

Which are more common autosomal dominant or autosomal recessive alleles?

Back 191

AR disorders are less common than AD disorders, but heterozygote carriers are much more common in the general population.

Front 192

What hamartoma syndrome presents by the late 20s with macrocephaly, trichilemmomas and papillomatous papules and increases risk of cancers?

Back 192

Cowden Syndrome

Front 193

What is the lifetime risk of developing breast cancer in Cowded Syndrome? and when does it present?

Back 193

25-50% lifetime risk presents between 38 and 46 years.

Front 194

What is the lifetime risk of
- breast cancer
- thyroid cancer
- endometrial cancer
from Cowden Syndrome?

Back 194

25-50% breast
10% thyroid (not medullary)
5-10% endometrial

Front 195

What syndrome is characterized by
-macrocephaly
-intestinal hamartomatous polyposis
- lipomas
- pigmented macules of the glans penis

Back 195

Bannayan-Riley-Ruval caba Syndrome

Front 196

What synddrome is highly variable involving congenital malformations and hamartomatous overgrowth of mult tissues, connective tissue nevis, epidermal nevi and hyperostoses.

Back 196

Proteus Syndrome

PS like is similar but don't meet diagnostic criteria)

Front 197

What are the 3 ways retinoblastoma occurs genetically/two-hit?

Back 197

1) loss of both copies of RB1 gene
2) two somatic mutations in the same cell
3) inherited germline mutation and secondary somatic mutation in same cell.

Front 198

What syndromes do cafe-au-lait spots occur in?

Back 198

Neurofibromatosis and
McCune-Albright Syndrome

Front 199

What is the most appropriate age at which surgical correction of undescended testes take place?

Back 199

1 year of age - some experts recommend months.

Front 200

How frequently do boys who have retractile testes in infancy develop an acquired undescended testes in middle to late childhood?

Back 200

1/3 of the time

Front 201

What is the term that occurs in cyanotic heart conditions that results from right-to-left shunting of blood such that an embolus from systemic venous circulation gains access to cerebral circulation?

Back 201

Paradoxic emboli

Front 202

Which is more common to cause a stroke in a patient with cyanotic heart disease? Polycythemia or Anemia?

Back 202

Anemia

Front 203

What condition presents with poor executive function and emotional lability after a period of normal and cognitive development?

Back 203

Adrenoleukodystrophy

Front 204

What is the mean onset of age of adrenoleukodystrophy?

Back 204

7 years old

Front 205

How does adrenoleukodystrophy progress?

Back 205

More severe visual, cognitive and motor problems involving spasticity and incoordination. A vegatative state and death follows.

Front 206

How is adrenoleukodystrophy inherited?

Back 206

X linked mutation in the ABCD 1 gene (defective oxidation of longchain fatty acids)

Front 207

When does amiotic band sequence cause its damage during gestation?

Back 207

Prior to 12 weeks

Front 208

What is the most frequently documented cause of mental retardation?

Back 208

Fetal Alcohol Syndrome

Front 209

What are the three categories of fetal alcohol syndrome diagnoses in addition to known maternal alcohol use?

Back 209

1) Facial
2) Pre or postnatal growth deficiency
3) Cognitive abnormality

Front 210

What are the facial features associated with fetal alcohol syndrome?

Back 210

-shortened palpebral fissures
-epicanthal folds
-hypoplastic nasal root
-short upturned nose
-hypoplastic or absent philtrum
-thin upper lip
-midface hypoplasia

Front 211

What are the growth features associated with fetal alcohol syndrome?

Back 211

wt < 10th percentile
microcephaly
length/height ratio < 10th percentile

Front 212

What syndrome presents as growth defiiciency, developmental delays, craniofacial anomalies & hypoplastic phalangels/nails

Back 212

Fetall hydantoin syndrome

Front 213

What syndrome is characterized by nasal hypoplasia and stippled epiphyses?

Back 213

Fetal warfarin syndrome

Front 214

What is characterized by:
-blue sclera
-delayed fontanelle closure
-hyperextensible joints
-hearing loss
-stature normal or near normal
-multiple fractures
-osteopenia of long bones
-wormian bones (bones without sutures)
-decreased synthesis of type 1 collagen

Back 214

Osteogenesis Imperfecta Type 1

Front 215

What is characterized by:
-newborns with numerous fractures
-severe short stature
-blue sclera at birth, but lighten with age
-neurologic complications
-hydrocephalus
-basilar skull invagination
-inability to bear weight or ambulate
-mutation of the COL1A1 geneture

Back 215

Osteogenesis Imperfecta Type 3

Front 216

What is characterized by:
-white sclera
-delayed closure of fontanelle
-fractures present at birth
-shorter than average stature
-tibial bowing
-dentinogenisis
-mutation of the COL1A2 gene

Back 216

Osteogenesis Imperfecta Type 4

Front 217

Which form of osteogenesis imperfecta has the most neurologic complications?

Back 217

Type 3

Front 218

Which type of osteogenesis imperfecta has the most tibial bowing?

Back 218

Type 4

Front 219

Which type/types of osteogenesis imperfecta arise from a mutation on the COL1A1 gene?

Back 219

Type 2 & 3

Front 220

Which types of osteogenesis imperfecta have blue sclera? How do they differ?

Back 220

Types 1 & 3

Type 1 stays dark blue
Type 3 lightens with age

Front 221

What is the incidence and inheritance pattern of Marfan Syndrome?

Back 221

Marfan Syndrome affects 1/5000 individuals, is Autosomal Dominant and affects boys and girls equally

Front 222

What is characterized by:
-high arched palate
-dislocated lens
-pectus carinatum or excavatum
-mitral valve prolapse
-cardiac complications
-can affect eyes, circulatory system, skeleton, lungs and dura

Back 222

Marfan Syndrome

Front 223

What causes the most deaths in Marfan Syndrome?

Back 223

Cardiac complications - most commonly aortic root dilatation and rupture

Front 224

What other pathophysiologic entity can appear like Marfan Syndrome and must be ruled out before a diagnosis of Marfans is made?

Back 224

Homocystinuria

Rule out by checking for the absence of homocystine in the urine without pyridoxine supp

Front 225

What are the cardiac guidelines for management of children with Marfan Syndrome?

Back 225

Annual or semiannular ECHO
Beta-blocker
Competitive exercise avoidance
Decrease degree of curvaure and deformity cause by scoliosis with induction of early puberty (in some recommendations)

Front 226

What are the major skeletal manifestations of Marfan Syndrome?

Back 226

-pectus carinatum (pigeon breast)
-pectus excavatum (funnel chest)
-reduced upper and lower segment ratio (arm-span to height ratio)
-wrist sign
-thumb sign
-pes planus
-scoliosis (>20%)

Front 227

How is the diagnosis of Marfan Syndrome made?

Back 227

Clinical diagnosis based on major criteria in at least 2 different organ systems and minor criteria in a 3rd without family history.

With history only one major & one minor manifestation in a second organ system.

Front 228

What chromosomal anomaly is present in individuals with Marfan Syndrome?

Back 228

Presence of a mutation in the gene that encodes fibrillin-1

FBN1

Front 229

Where do pseudotumors commonly occur in patients with Ehlers-Danlos Syndrome?

Back 229

Heels, Elbows, Knees

from abnormal scarring

Front 230

What coagulation test will be abnormal in Ehlers-Danlos Syndrome?

Back 230

Capillary Fragility testing

Front 231

What increases the risk of aortic dilatation/dissection in women with Marfan Syndrome?

Back 231

Pregnancy

Front 232

What disorder is associated with progressive myoclonic epilepsy,
myopathy, dementia and hearing loss?

Back 232

MERRF
Myoclonic Epilepsy and Red-Ragged Fibers

Front 233

What are the major manifestations of Marfans?

Back 233

skeletal (pectus, wrist sign, thumb sign, pes planus, scoliosis, decreased extension of elbows, protrusioacetabuli)
ectopia lentis
dilatation of ascending aorta
dissection of ascending aorta
lumbosacral dural ectasia (dilation)

Front 234

How is MERRF (Myoclonic Epilepsy and Red Ragged Fibers) inherited?

Back 234

Mutation in the mitochondrial genome

Front 235

What is MELAS?

Back 235

Mitochondrial
Encephalopathy with
Stroke-like episodes and
Lactic Acidosis

Front 236

How is MELAS inherited?

Back 236

Mutations in the mitochondrial genome.

Front 237

What syndrome presents with anemia, neutropenia, pancreatic dysfunction and myopathy in infants?

Back 237

Pearson Syndrome

Front 238

How is Pearson Syndrome inherited?

Back 238

Mutations in mitochondrial genome

Front 239

What presents with opthalmoplegia, retinitis pigmentosa, myopathy and cardiac conduction defects?

Back 239

Kearns-Sayre Syndrome

Front 240

How is mitochondrial inheritance unique? What % of a mothers children wll get the mutation? What % of fathers?

Back 240

All comes from Mom.

Mom's kids get it 100% of the time. Dad's never do.

Front 241

What is the term for the variable proportion of mutant and normal mtDNA within a cell or tissue?

Back 241

Heteroplasmy

Front 242

When does MELAS present?

Back 242

Anytime between the age of a toddler to adolescent

Front 243

What presents with basal ganglia defects, hypotonia and optic atrophy in infancy or early childhood?

Back 243

Leigh Disease

Front 244

How is Leigh Disease inherited?

Back 244

Mitochondrial mutation

Front 245

What term refers to the state in which all mt mtDNA are identicle?

Back 245

Homoplasmy

Front 246

What commonly presents with metabolic encephalopathy, cardiac failure, liver failure and/or lactic acidosis?

Back 246

Mitochondrial disorders

Front 247

Although mitochondrial disorders are not common, what major complications do they commonly cause?

Back 247

CVA
Deafness
Diabetes

Front 248

What is the most common inherited mental retardation syndrome and how common is it?

Back 248

Fragile X

occurs in 1/1650 males

Front 249

How is Fragile X inherited?

What makes it unique?

Back 249

X linked inheritance
- 30% of carrier females have similar phenotypes to males
-a normal male can pass to all daughters with 50% of their boys being affected.

Front 250

What is considered Full Mutation, Premutation and Normal in Fragile X?

Back 250

Normal = 6-50 repeats
Premutation 55-200 repeats
Full Mutation >200 repeats

Front 251

What Syndrome is characterized by mental retardation, large head, long face with large ears, large hands and feet, macroorchidism, and hyperextensible joints?

Back 251

Fragile X - full mutation

Front 252

What chromosomal anomaly is characterized by
- bile duct paucity with cholestasis
-pullmonary valve stenosis
-peripheral artery stenosis
-ocular defects (posterior embryotoxon)
-skeletal defects
-butterfly vertebrae
-triangular facies with pointed chin
-long nose with broad nose (midnose)

Back 252

20p12- (deletion)

Alagille syndrome

Front 253

What type of liver involvement occurs in Alagille Syndrome? (20p12-).

Back 253

-presents in 1st 3 mos of life
-cholestasis
-jaundice
-pruritis
-paucity of bile ducts observed (histologically)
-and some develop liver failure

Front 254

What are the most common cardiac manifestations associated with Alagille Syndrome?

Back 254

Peripheral and branch pulmonic stenosis (67% of patients) and Tetrology of Fallot (7-16%)

Front 255

What is posterior embryotoxon associated with and what is it?

Back 255

Associated with Alagille Syndrome and is a developmental abnormality marked by a prominent white right of Schwalbe and iris strands that partially obscure the chamber angles.

Front 256

How is Alagille Syndrome inherited?

Back 256

Autosomal Dominant
(20p12- deletion)

Front 257

When do you need to order thyroid functions in patients with Down Syndrome?

Back 257

birth, 3, 6, and 12 months and then annually.

Front 258

What problems occur in later life in patients with Down Syndrome (30s-40s)

Back 258

Diabetes
Thyroid disorders
Atlanoaxial subluxation
Cataracts
Leukemia
Seizures
Cognitive dysfunction
Dementia or early Alzheimers

Front 259

What are the AAP Guidelines for anticipatory guidance/screenings in children with Down Syndrome?

Back 259

- All routine immunizations
- Cardiac Eval with ECHO as newborn
- Opthalmology eval before 6 mos old
- Hearing eval by 6 mos old
- Thyroid-newborn screen then yearly T4, TSH throughout life
-Vision Screening at age 4

Front 260

If the patient has 3 complete copies of chromosome 21 and the mother is < 35 years of age, what is her risk of having another child with trisomy 21?

Back 260

1%

Front 261

If a patient has 3 complete copies of chromosome 21, and the mother is > 35 years of age, what is the risk of her having another child with Trisomy 21?

Back 261

Similar to the risk for any woman her age.

Front 262

If a mother has a balanced translocation of chromosome 21, what is the recurrence risk of Trisomy 21? (ie, the next chld)

Back 262

10-15%

Front 263

If a father has a balanced translocation of chromosome 21, what is the recurrence risk of Trisomy 21? (ie the next child)

Back 263

1-2%

Front 264

What Syndrome is characterized by - IUGR, MR, high forehead, microcephaly, small face and mouth, short sternum, rocker bottom feet, clufoot, clenched fist overlapping fingers,hypoplastic nails, structural heart defects

Back 264

Edwards Syndrome

Front 265

What is the second most common autosomal trisomy?

Back 265

Edwards Syndrome (Trisomy 18)

Front 266

Of the children born with Edwards Syndrome, what percents have what life expectancies?

Back 266

50% die within the 1 st wk
40% dying by 1 year of age

(most die of central apnea)

Front 267

What is the highest level of functioning that occurs in Edwards Syndrome?

Back 267

the level of a 2 year old

Front 268

What is the ratio of GIRLS to BOYS born with Edwards Syndrome?

Back 268

4:1

Front 269

What percennt of cases of Edwards Syndrome are due to 3 complete copies of chromosome 18%

Back 269

95% with the other 5% due to mosaicism or partial trisomy of the long arm of chromosome 18.

Front 270

What is the third most common autosomal trisomy in humans, and how common is it?

Back 270

Patau Syndrome
(Trisomy 13)

1/20,000 - 1/25,000 live births

Front 271

What is the frequency of Trisomy 18 (Edwards Syndrome)?

Back 271

1/6000

Front 272

What syndrome is characterized by: orofacial cleft, micropthalmia, postaxial polydactyly of limbs, holoprosencephaly, heart malformations, hypoplastic or absent ribs, genital anomalies, abd wall defects, cutis aplasia?

Back 272

Patau Syndrome
(Trisomy 13)

Front 273

What is survival/life expectancy in infants born with Patau Syndrome (Trisomy 13)?

Back 273

Median Survival is 2.5 days
80% dies within the 1st month
Only 5% survive the 1st 6 mos.

Front 274

What problems occur in survivors with Patau Syndrome (Trisomy 13)?

Back 274

Severe MR
Seizures
Failure to Thrive

Front 275

What is relatively the rarest of the trisomies?

Back 275

Mosaic Trisomy 8

Front 276

What is characterized by
- long face
- high forehead
- a thick, everted lower lip
- deep palm and sole creases
- low-set ears

Also bone, joint and renal malformations and increased risk of AML.

Back 276

Mosaic Trisomy 8

Front 277

What chromosomal anomaly is characterized by
- large, low-set ears
- micrognathia
- hypertonia
-downward-slanting palpebral fissures
- skeletal anomalies

Back 277

21q-

(long arm deletion)

Front 278

What chromosomal anomaly is characterized by
-only 20% having severe abnormalities
-80% have only mild retardation and minor anomalies
-the 20% have severe ocular and brain anomalies (holopprosencephaly) cleft lip/palate and mental retardation
- IgA deficiency in majority of cases.

Back 278

18 p-

(short arm deletion)

Front 279

What Syndrome is characterized by:
-Greek helmet facies (ocular hypertelorism, prominent glabella and frontal bossing)
-Growth deficiency
-Microcephaly
-Beaked nose
-Short philtrum
-Hypotonia
-Congenital cardiac anomalies
-Seizures

Back 279

4 p -

(Wolf-Hirschhorn Syndrome)

Front 280

How frequent does (4p- Syndrome) Wolf-Hirschhorn Syndrome occur?

Back 280

1/50,000 births and is the most common in girls

Front 281

What Syndrome is characterized by:
-moon face with telecanthus (widespaced eyes)
-down slanting palpebral fissures
-hypotonia
-short stature
-microcephaly
-high-arched palate
- wide and flat nasal bridge
-mental retardation
-cardiac manifestations.

Back 281

5p -

(Cri-Du-Chat Syndrome)

Front 282

What chromosome is affected in Wolf-Hirschhorn-Syndrome?

Back 282

4 p-

(deletion short arm)

Front 283

What syndrome is caused by 4 p- deletion?

Back 283

Wolf-Hirschhorn-Syndrome

Front 284

What syndrome is caused by 5p- deletion?

Back 284

Cri-Du-Chat Syndrome

Front 285

What chromosome anomaly causes cri-di-chat syndrome?

Back 285

5 p- (deletion short arm)

Front 286

What Syndrome is characterized by
- atretic or narrowed ear canals
-frog-like position of legs (flexed, ext rot and hyperabduction)
-depressed midface
- protruding manible
- deep-set eyes
-Everted lower lip (carp-like mouth)
-mental retardation

Back 286

De Grouchy Syndrome (18 q -)

Front 287

What chromosomal anomaly causes De Grouchy Syndrome?

Back 287

18q- deletion of long arm

Front 288

What syndrome is caused by 18 q- (deletion)?

Back 288

DeGrouchy Syndrome

Front 289

What chromosomal anomaly is characterized by:
-trigonocephaly
-discrete exophalmos
-arched eyebrows
-short neck with pterygium coolli (web)
- bong fingers and toes
-Cardiiac abnormalities

Back 289

9 p-
(deletion of short arm)

Front 290

What chromosomal anomaly is characterized by
-low birthweight
-failure to thrive
-severe mental retardation
-ocular manifestations
-hypoplastic hands
-absent thumbs with syndactyly

Back 290

13 q-

Front 291

What syndrome is caused by 15q11-13 microdeletion?

Back 291

Angelmans if it is maternally derived
Prader-Willi if it is paternally derived

Front 292

What syndrome is characterized by
-jerky ataxic movements
-characteristic gait
-hypotonia
-face hair
-midface hypoplasia
-prognathism (large chin, mandible)
-seizures
-inappropriate bouts of laughter
-severe MR, absent severely delayed speech

Back 292

Angelman Syndrome

Front 293

What chromosomal anomaly is characterized by
-severe hypotonia at birth
-obesity after failure to thrive
-short stature
-small hands and feet
-hypogonadism
-usually mild mental retardation

Back 293

Prader-Willi Syndrome

Front 294

What syndrome is caused by a microdeletion on the long arm of chromosome 7? (7q11.23-)

Back 294

Williams Syndrome

Front 295

What chromosomal anomaly is characterized by
-periorbial fullness with prominent, down-turned lower lip
-friendly (cocktail party) personality
-stellate pattern of the iris
-strabismus
-supravalvular aortic stenosis
-mental retardation
-hypercalcemia

Back 295

Williams Syndrome (7q11.23-)

Front 296

What chromosomal anomaly causes Williams Syndrome?

Back 296

7q11.23-

In 95% they are missing the elastin gene from one of their two copies of chromosome number 7

Front 297

What chromosomal anomaly is characterized by GU malformations, mental retardation, aniridia and Wilm's tumor?

Back 297

11p13-

(WAGR Syndrome)

Front 298

What causes WAGR Syndrome?

Back 298

11p13- deletion

Occurs due to absence of two possible genes PAX6 and WilmsTumor1(WT1)

Front 299

What are the characteristics of WAGR Syndrome?

Back 299

-Wilms Tumor (up to 50% of cases, usuall by age 3)
-Aniridia
-Male genital hypoplasia (hypospadias, cryptochidism, small penis, hypoplastic scrotum)
-MR (IQ <35 to nl)
-Gonadoblastoma
-Long face
-Upward-slanting palpebral fissures
-Ptosis
-Beaked nose
-Poorly formed ears

Front 300

What syndrome is characterized by
poorly formed ears
beaked nose
ptosis
upward slanting palpebral fissures
long face
gonadoblastoma
mental retardation
male genital hypoplasia
aniridia
Wilm's tumor

Back 300

WAGR Syndrome (11p13-)

Front 301

What syndrome has autosomal dominant inheritance inheritance and is caused by mutation in the JAG1 gene?

Back 301

Alagille Syndrome
(20p12-)

Front 302

What is characterized by 3 distinct disorders:

Mild cognitive/behavioral deficits
-premature ovarian failure
-neurodegenerative disorder of older adult carrier with associated tremor/ataxia

Back 302

Premutation carriers of Fragile X (55-200 CGG repeats)

Front 303

What is FXTAS?

Back 303

Fragile X associated tremor/ataxia syndrome (55-200 CGG repeats)

Front 304

What is characterized in females by increased emotional problems (anxiety/dep), premature ovarian failure (~20%), ovarian dysfunction (~20%), and mild decrease in FMR1 protein

Back 304

Females in premutation range of Fragile X (>100CGG repeats)

Front 305

How common is FXTAS in carriers of Fragile X?

Back 305

-mostly in male carriers
-usually >50 years of age
->30%of male carriers develop symptoms
-significant variability in progression of symptoms
-clinical criteria:intention tremor and gait ataxia, parkinsonism

Front 306

How is myotonic dystrophy inherited?

Back 306

It is autosomal dominant with variable age of onset and variable severity

Front 307

What is characteized by
-autosomal dominant inheritance
-myotonia with progressive weakness and wasting-facial muscles and grip
-other involved organs (eye, endocrine, premature balding & mental retardation)

Back 307

myotonic dystrophy

Front 308

What is characterized by
-marked hypotonia
-mental retardation in 60-70%
-neonatal respiratory distress
-feeding difficulties
-talipes
-possible neonatal death?

Back 308

Congenital myotonic dystrophy

Front 309

What mutation causes myotonic dystropy?

Back 309

CTG mutation - repeat in the 3' untranslated region of myotonin kinase gene on chromosome 19

Front 310

What chromosome is associated with myotonic dystrophy?

Back 310

Chromosome 19

Front 311

What number of CTG repeats is normal on chromosome 19, and what number is associated with myotonic dystrophy?

Back 311

Normal 5-35 repeats

Myotonic Dystrophy 50-several thousand repeats

Front 312

What infants are most affected by myotonic dystrophy?

Back 312

Those that inherit their trinucleotide repeat expansion from their mother.

Front 313

What can cause
-cataracts
-testicular atrophy
-diabetes mellitus
-mental retardation
-premature balding in males

Back 313

Myotonic Dystrophy

Front 314

What causes most genetic disorders?

Back 314

multiple genetic and environmental factors

Front 315

What is the most common cause of isolated major anomalies observed in the newborn?

Back 315

Multifactorial inheritance

Front 316

Examples of what type of inheritance include neural tube defects, heart defects, schitzophrenia, hyperlipidemia, cleft palat and clubfoot?

Back 316

Multifactorial inheritance

Front 317

What are the clinical criteria for neurofibromatosis type 1? (2 of 7 criteria)

Back 317

1st degree relative with type 1
>5 cafe au lait spots >0.5 cm in pre-puberal and 1.5 cm in post-pubertal
>1 neurofibromas of any type or aplexiform neurofibroma
Frecklin in axillary or inquinal areas
Optic glioma
>1 lisch nodules

Front 318

What are benign, peripheral nerve sheath tumors that are a collection of schwann-like cells, fibroblasts and extracellular matrices?

Back 318

Neurofibromas

Front 319

How are 60% of cases of neurofibromatosis type 1 inherited andhow are the remainder inherited?

Back 319

60% are de novo AD mutations, the rest have AD inheritance

Front 320

What type of neurofibromatosis is more common type 1 or 2?

Back 320

Type 1 is more common

Front 321

How is neurofibromatosis type 2 inherited?

Back 321

Autosomal Dominant

Front 322

How old are kids at presentation of neurofibromatosis type 1 and type 2?

Back 322

type 1 - most dx by age 10

type 2 - mean age 30 years

Front 323

What is a lethal sequelae of Rett Syndrome?

Back 323

Cardiac arrythmia (secondary to autonomic dysfunction)

Front 324

What is the genetic definition that refers to 2 different alleles at a locus on a pair of homologous chromosomes?

Back 324

Heterozygous

Front 325

What type of inheritance does Marfan syndrome have?

Back 325

Pleiotropic effects

Front 326

What is the genetic definition that refers to genes that produce many effects?

Back 326

Pleiotropic

Front 327

What type of inheritance does Treacher-Collins Syndrome have?

Back 327

Autosomal dominant with variable expressivity

Front 328

What genetic definition refers to reduced or incomplete genetic expression 100% of the time?

Back 328

Incomplete penetrance

Front 329

What genetic definition refers to the ability of a known disease-causing genotype to be expressed or to exhibit the disease phenotype.

Back 329

Penetrance

Front 330

What genetic definition refers to the observed expression (physical, biochemical, or physiological findings) of the genotype or gene mutation?

Back 330

Phenotype

Front 331

10% of patients with retinoblastoma who have an autosomal dominant gene mutation causing retinoblastoma do not develop retinoblastoma. Why is that?

Back 331

Because retinoblastoma is autosomal dominant, but only has 90% penetrance.

Front 332

What genetic definition refers to the genetic constitution or different forms of a gene (alleles) at a given locus?

Back 332

Genotype

Front 333

What genetic definition refers to conditions that cluster in families and can include nongenetic as well as genetic conditions?

Back 333

Familial

Front 334

What genetic definition refers to conditions that can be transmitted from parent to offspring?

Back 334

Hereditary

Front 335

What genetic definition refers to a condition or anomaly present at birth?

Back 335

Congenital

Front 336

True or False
Familial refers to conditions that "cluster" in families and can include genetic an nongenetic conditions

Back 336

True

Front 337

True or False
All hereditary conditions are genetic so all genetic conditions are hereditary?

Back 337

False

Front 338

True or False
All hereditary conditions are familial, but not all genetic conditions are familial.

Back 338

False

Front 339

What type of inheritance does retinoblastoma have?

Back 339

Autosomal dominant with 90% penetrance

Front 340

What genetic definition refers to individuals who have the same genetic condition (and sometimes even the exact genotype), but present with different phenotypes?

Back 340

Variable expressivity

Front 341

How often are children with severe mental retardation going to have cerebral dysgenesis on MRI?

Back 341

10-15%

Front 342

What syndrome is most often associated with bilateral closure of the coronal sutures?

Back 342

Crouzon syndrome

Front 343

What syndrome involves premature closure of multiple sutures and syndactyly?

Back 343

Apert Syndrome

Front 344

What syndrome is associated with multiple fusions of cranial sutures, syndactyly, mental retardation and possible congenital heart disease, orthopedic abnormalities and corneal opacities?

Back 344

Carpenter Syndrome

Front 345

What IQ corresponds with mild mental retardation?

Back 345

50-75

Front 346

Mild mental retardation occurs how often?

Back 346

20-30/1000

Front 347

Is mild mental retardation more common in boys or girls?

Back 347

boys

Front 348

How often is mild mental retardation associated with an identifiable chromosomal abnormality?

Back 348

4-8%

Front 349

How often does severe mental retardation occur?

Back 349

1-4/1000

Front 350

Is mental retardation associated with socioeconomic factors?

Back 350

Mild MR is

Severe MR is NOT

Front 351

How often is severe mental retardation due to chromosomal abnormalities?

Back 351

30%

Front 352

What is the most common chromosomal abnormality that causes severe mental retardation?

Back 352

Down Syndrome

Front 353

How often are CNS injuries responsible for severe mental retardation?

Back 353

15-20%

Front 354

What genetic definition refers to identical alleles at a particular gene locus?

Back 354

Homozygous

Front 355

What genetic definition refers to all chromosomes except the X or Y chromosome?

Back 355

Autosome

Front 356

What is the genetic definition when there are extra or missing autosomes or sex chromosomes?

Back 356

Aneuploidy

Front 357

What is the genetic term that refers to a structural birth defect or congenital malformation?

Back 357

Anomaly

Front 358

What is the genetic term for anomalies of several different structures that lie together in the same local body region during embryonic development?

Back 358

Complex

Front 359

What genetic definition refers to a recognizable pattern of structural defects, often with a predictable natural history that can be identified amongst several patients?

Back 359

Syndrome

Front 360

Is Pierre-Robin anomaly a
-complex
-phenotype
-syndrome or
-sequence?

Back 360

Sequence

Front 361

What is the most common single gene abnormality THAT LEADS to clinical disorder? (type of inheritance)

Back 361

Autosomal dominant

Front 362

Is Williams anomaly a
-complex
-phenotype
-syndrome or
-sequence?

Back 362

Syndrome

Front 363

Is Pena-Shokeir a
-complex
-phenotype
-syndrome or
-sequence?

Back 363

Phenotype

Front 364

Is "limb-body wall" anomaly a
-complex
-phenotype
-syndrome or
-sequence?

Back 364

Complex

Front 365

What is the genetic definition that refers to a pattern of multiple anomalies that result from a single identifiable event in development?

Back 365

Sequence

Front 366

Is Cornelia de Lange a
-complex
-phenotype
-syndrome or
-sequence?

Back 366

Syndrome

Front 367

What percentage of a heterozygous parent with an autosomal dominant disorder will pass the disorder on to his/her child?

Back 367

50%

Front 368

What type of inheritance with have:
-disorders in one or mor sibs, but not in other generations
-M & F are equally affected
-M & F can each transmit the altered allele
-the risk for 2 heterozygotes to pass on is 1/4
-Consanguinity increase the risk of having an offspring with this type of disorder

Back 368

Autosomal recessive

Front 369

How do you calculate the probability or population frequencies of various diseases when there is a high carrier frequency in the population?

Back 369

Multiply the frequency for each parent then multiply by 1/4 because the mode of inheritance is autosomal recessive.

Front 370

What types of inheritance will have
-both sexes equally affected
-both sexes can transmit to kids
-no generation is skipped
-every affected person in family has a parent with the disorder (except de novo mutations)
-You will see Father to Son transmission?

Back 370

Autosomal Dominant

Front 371

What is the genetic transmission of neurofibromatosis Type I?

Back 371

60% are de novo mutations which are then passed on by autosomal dominant inheritance

Front 372

Marfan syndrome and achondroplasia have what risk factor in common?

Back 372

Advanced PATERNAL age

(as is true with most AD diseases)

Front 373

What should you suspect when a "normal" parent has more than one child affected with an autosomal dominant or X-linked condition?

Back 373

Germline mosaicism

Front 374

Which are more common, autosomal dominant or autosomal recessive alleles?

Back 374

Autosomal recessive

While AR disorders are less common than AD disorders, there are many more heterozygote carriers of AR genes in the general population.

Front 375

What hamartoma syndrome presents by the late 20s with macrocephaly, trichilemmomas and papillomatous papules and increases risk of cancers?

Back 375

Cowden Syndrome

Front 376

What is the lifetime risk of developing breast cancer
in Cowden Syndrome and when does it present?

Back 376

25-50% lifetime risk

Presents between 38 and 46 years of age

Front 377

What is the lifetime risk of developing thyroid cancer in Cowden Syndrome?

Back 377

10%

Thyroid cancer IS NOT medullary

Front 378

What is the lifetime risk of developing endometrial cancer in Cowden Syndrome?

Back 378

5-10%

Front 379

What syndrome is characterized by
-macrocephaly
-intestinal hamartomatous polyposis
-lipomas
-pigmented macules of the glans penis?

Back 379

Bannayan-Riley-Ruval caba Syndrome

Front 380

What syndrome is highly variable involving congenital malformations and hamartomatous overgrowth of multiple tissues, connective tissue nevi, epidermal nevi and hyperostoses?

Back 380

Proteus Syndrome

(PS-like is similar, but doesn't meet full diagnostic criteria for PS)

Front 381

What are the 3 ways retinoblastoma occurs genetically/two-hit?

Back 381

1- loss of both copies of RB1 gene
2- two somatic mutations in the same cell
3- inherited germline mutation and secondary somatic mutation in the same cell

Front 382

What syndromes do cafe-au-lait spots occur in?

Back 382

Neurofibromatosis

McCune-Albright Syndrome

Front 383

What is the most appropriate age at which surgical correction
of undescended testes take place?

Back 383

1 year of age


some experts recommend 6 months

Front 384

How frequently do boys who have retractile testes in infancy defelop an acquired undescended teste in middle to late childhood?

Back 384

1/3 of the time

Front 385

What is the term that occurs in cyanotic heart conditions that result from right-to-left shunting of blood such that an embolus from systemic venous cirulation gains access to cerebral circulation

Back 385

Paradoxic emboli

Front 386

Which is more common to cause a stroke in a patient with cyanotic heart disease - polycythemia or anemia?

Back 386

Anemia

Front 387

What condition presents with poor executive function and emotional lability after a period of normal motor and cognitive development?

Back 387

Adrenoleukodystrophy

Front 388

What is the mean onset of age of adrenoleukodystrophy?

Back 388

7 years old

Front 389

How does adrenoleukodystrophy progress

Back 389

More severe visual cognitibe and motor problems involving spasticity and incoordination. A vegetative state and death follows.

Front 390

How is adrenoleukodystrophy inherited?

Back 390

X-linked mutation in the ABCD 1 gene (defective oxidation of long-chain fatty acids)

Front 391

When does amniotic band sequence cause its damage during gestation?

Back 391

Prior to 12 weeks

Front 392

What is the most frequently documented cause of mental retardation?

Back 392

Fetal Alcohol Syndrome

Front 393

What are the three criteria in addition to known maternal alcohol use that are used to diagnose fetal alcohol syndrome?

Back 393

1 - facial
2 - pre or postnatal growth deficiency
3 - cognitive abnormality

Front 394

What are the facial features associated with fetal alcohol syndrome?

Back 394

1- shortened palpebral fissures
2 - epicanthal folds
3 - hypoplastic nasal root
4 - short upturned nose
5 - hypoplastic or absent philtrum
6 - thin upper lip
7 - midface hypoplasia

Front 395

What are growth features associated with fetal alcohol syndrome?

Back 395

wt < 10th percentile
microcephaly
length/height ratio <10 th percentile

Front 396

What syndrome presents as growth deficiency, deelopmenal delays, craniofacial anomalies and hypoplastic phalanges/nails

Back 396

Fetal hydantoin syndrome

Front 397

What syndrome is characterized by nasal hypoplasia and stippled epiphyses?

Back 397

Fetal warfarin syndrome

Front 398

What are the six classic findings of tuberous sclerosis?

Back 398

1- Ash leaf hypopigmented macules (90%)
2 - Shagreen patches
3- facial angiomas
4- forehead plagues
5- ungual (nail) and gingival fibromas
6 - polycystic kidney disease (TSC2)

Front 399

What is characterized by
- blue sclera
- delayed fontanelle closure
- hyperextensible joints
- hearing loss
- stature normal or near normal
- multiple fractures
- osteopenia of long bones
- wormian bones (bones without suture)
- decreased synthesis of Type 1 collagen

Back 399

Osteogenesis Imperfecta Type 1

Front 400

What is characterized by
- newborns with numerous fractures
- severe short stature
- blue sclera at birth but lighten with age
- neurologic complications
- hydrocephalus
- basilar skull invagination
- inability to bear weight or ambulate
- mutation of the COLA1 gene

Back 400

Ostenogenesis Imperfecta
Type 3

Front 401

What is characterized by
- white sclera
- delayed closure of fontanelle
- fractures present at birth
- shorter than average stature
- tibial bowing
- dentinogenesis
- mutation of the COLA2 gene

Back 401

Ostenogenesis Imperfecta
Type 4

Front 402

Which form of osteogenesis imperfecta has the most neurologic complications?

Back 402

Type 3

Front 403

Which type of osteogenesis imperfecta has the most tibial bowing?

Back 403

Type 4

Front 404

Which type/types of Osteogenesis imperfecta arise from a mutation on the COLA1 gene?

Back 404

Types 2 & 3

Front 405

Which types of osteogenesis imperfecta have blue sclera? How do they differ?

Back 405

Types 1 and 3

Type 1 stays dark blue
Type 3 lightens with age

Front 406

What is the incidence and inheritance pattern of Marfan Syndrome?

Back 406

Marfan Syndrome affects 1/5000 individuals, is Autosomal Dominant and affects boys and girls equally

Front 407

What is characterized by
- high arched palate
- dislocated lens
- pectus carinatum or excavatum
- mitral valve prolapse
- cardiac complications
- can affect eyes, circulatory system, skeleton, lungs and dura.

Back 407

Marfan Syndrome

Front 408

What causes the most deaths in Marfan Syndrome?

Back 408

Cardiac complications - most commonly aortic root dilatation and rupture

Front 409

What other pathopysiologic entity can appear like Marfan Syndrome and must be ruled out before a diagnosis of Marfans is made?

Back 409

Homocystinuria (Rule out by checking for the absence of homocystine in the urine without pyridoxine supplementation)

Front 410

What are the cardiac guidelines for management of children with Marfan Syndrome?

Back 410

A - Annual or semiannular ECHO
B - beta-blocker
C - competitive exercise avoidance
D - decrease degree of curvature & deformity cause by scoliosis with induction of early puberty (in some recommendations)

Front 411

What are the major skeletal manifestations of Marfan Syndrome?

Back 411

- pectus carinatum (pigeon breast)
- pectus excavatum (funnel chest)
- reduced upper and lower segment ratio (arm-span-to-height-ratio)
- wrist sign
- thumb sign
- pes planus
- scoliosis (>20%)

Front 412

How is the diagnosis of Marfan Syndrome made?

Back 412

Clinical diagnosis based on major criteria in at least 2 different organ systems and minor criteria in a 3rd without family history

With family history just one major and one minor (2nd organ system)

Front 413

What chromosomal anomaly is present in individuals with Marfan Syndrome?

Back 413

Presence of a mutation in the gene that encodes fibrillin - 1

FBN1

Front 414

Where do pseudotumors commonly occur in patients with Ehlers-Danlos Syndrome?

Back 414

Heels
Elbow > from abnormal scarring

Knees

Front 415

What coagulation test will be abnormal in Ehlers-Danlos Syndrome?

Back 415

Capillary Fragility testing

Front 416

What increases the risk of aortic dilatation/dissection in women in Marfan Syndrome?

Back 416

Pregnancy

Front 417

What disorder is associated with progressive myoclonic epilepsy, myopathy, demetia hearing loss?

Back 417

MERRF
-myoclonic
-epilepsy
-red-ragged
-fibers

Front 418

What are the major manifestions of Marfans
- skeletal (pectus, decreased arm span to height ratio, wrist sign, thumb sign, pes planus, scoliosis, decreased extension of elbows protrsioacetabuli)
-ectopia lentis
-dilatation of ascending aorta
-dissection of ascending aorta
- lumbosacral dural ectasia (dilation)

Back 418

Major Manifestations 2 are required with a 3rd minor if no family history. If history then 1 major and 1 minor

Front 419

What is the mathematical equation for sesitivity?

Back 419

TP/TP + FN

TP = true positivities
FN= false negatives.

Front 420

What is the mathematical equation for specificity?

Back 420

TN/FP + TN

TN = true negatives
FP = false positives

Front 421

What is the mathematical equation for positive predictive value?

Back 421

TP/TP = FP

TP = true positives
FP = false positives

Front 422

What is this mathematical equation for negative predictive value?

Back 422

total with disease/total

Front 423

What happens to sensitivity and specificity when you increase the threshold for normal?

Back 423

Increased threshold for normal causes more negative tests both true& false and therefore decreases sensitivity and increases specificity

Front 424

What happens to sensitivity and specificity when you decrease the threshhold for hormal?

Back 424

increase number of positives (true and false)
decrease number of negatives (true and false)
So decrease in specificity and increase in sensitivity

Front 425

What p-value is considered statistically significant?

Back 425

P-value of less than or equal 0.05 is considered statistically significant.

Front 426

What type of error occurs from concluding there is a difference when there is no difference (rejecting null hypothesis)?

Back 426

Type 1

Front 427

What type of error occurs from concluding there is no difference (fail to reject null hypothesis) when one exists.

Back 427

Type 2

Front 428

What is the retrospective analysis of many studies concerned with the same thing or topic?

Back 428

Meta-analysis

Front 429

What p-value is equivalent to a confidence interval of 99%?

Back 429

p < 0.01

Front 430

What is the classic presentation of McCune Albright in girls?

Back 430

Isolated vaginal bleeding

Front 431

What Syndrome affects endocrine skin and skeletal:
-due to missense mutation affecting cAMP
-affects TSH, LH, FSH, ACTH receptors
-expresses very differently in different people
-can cause precocious puberty, hyperthyroidism, cushing syndrome, giantism, acromegaly, phosphauria, ricets, osteomalacia, cardiac and liver damage.

Back 431

McCune Albright Syndrome

Front 432

What is a rare autosomal dominant disorder that appears between the ages of two and three and is NOT due to GnRH stimulation but a missense mutatio of the LH receptor activating Leydig cells.

Back 432

Familial Male
Gonadotropin- independent Precocious puberty

Front 433

What presents in infants with multiple pituitary defects like hypoglycemia, jaundice, micropenis and midline facial anomalies?

Back 433

Deficiency of TRH with deficiency of TSH

Occurs in 1/30,000 infants
Detected in 1/3 by neonatal screening

Front 434

How you treat familial male gonadotropin independent precocious puberty?

Back 434

Ketoconazole which inhibits 17,20-lyase and testosterone synthesis

Front 435

What skeletal findings are seen with congenital hypothyroidism?

Back 435

1-enlarged posterior fontanel
2-delayed bone maturation
3-absent distal femoral epipysis
4-malformed thoracic vertebrae (or 1st or 2nd lumbar)
5-large sutures seen on Xray

Front 436

What is the pseudohypertrophy associated with congenital hypothyroidism called?

Back 436

Kocher-Debre-Semelargne Syndrome

Front 437

How is muscle tone in infants with congenital hypothyroidism?

Back 437

Usually hypotonic but a few have pseudohypertrophy

Front 438

What presents with physical findings of enlarged posterior fontanelles, enlarged tongue (thick) edema of eyelids and hands?

Back 438

Congenital Hypothyroidism

Front 439

When is the full clinical picture of congenital hypothroidism present?

Back 439

3-6 mos of age - try to treat by 2 weeks of age to prevent problems

Front 440

What clinically presents during the first month of life with:
-feeding problems
-sluggishness
-lack of interest
-choking spells when nursing
-somnolence
-respiratory difficulty
-enlarged tongue
-edema, bradycardia
-cardiomegalyroi

Back 440

Congenital Hypothyroidism

Front 441

What is Schmidt syndromes?

Back 441

Autoimmune thyroiditis
Diabetes mellitus with or without adrenal cortical insufficiency.

Front 442

What syndrome presents as right quadrant pain from inflammation of the liver capsule from ascending pelvic infection?

Back 442

Fitz-Hugh-Curtis
(perihepatitis)

Front 443

What component of neurofibromatosis can cause hearing loss, tinnitus, imbalance and facial weakness?

Back 443

Vestibular Schwannomas

Front 444

What is characterized by
-numerous fractures
-severe bone deformity
-soft skull
-limb which are short and bowed
-ribs that are "beaded"
-"crumpled appearance" on Xray
-mutation of COLA1 gene which disrupts collagen formation.

Back 444

Osteogenesis Imperfecta