Mca, Derm & Neuromuscular: 100 Genetic Syndromes

Front 1

AARSKOG SYNDROME
Type, Gene, Inheritance

Back 1

MCA syndrome
FGD1 gene;
XLR (some AR,AD cases)

Front 2

ANTLEY-BIXLER SYNDROME
Type, Gene, Inheritance

Back 2

MCA Syndrome
POR gene; 7q11.2; NOTE: some say FGFR2
AR

Front 3

BARDET-BIEDL SYNDROME

Back 3

MCA Syndrome
BBS1, BBS10 (+11 genes); 11q13, 12q21.2, AR
AR (10% triallelic)
Features: cone-rod dystrophy, truncal obesity, postaxial polydactyly, MR, genital malformations (hypo), and renal dysfunction. Legally blind by age 15.5 yrs. Most learning difficulties, only a minority have severe impairment. Renal disease is a major cause of morbidity and mortality.
Clinical Tests: atypical pigmentary retinal dystrophy with early macular involvement, renal anomalies on US
Molecular Tests: Targeted mutation analysis: p.M390R BBS1 (18%-32% of BBS) and C91fsX95 BBS10 (10% of BBS).

Front 4

BRANCHIOOTORENAL SYNDROME

Back 4

MCA Syndrome
EYA1, SIX1 genes, 8q13.3, 14q23;
AD
Features: Ear and Kidney
malformations of the outer, middle, and inner ear associated with conductive, sensorineural, or mixed hearing impairment; branchial fistulae and cysts; and renal malformations, ranging from mild renal hypoplasia to bilateral renal agenesis
Clinical Tests: Temporal bone CT, hearing, renal US
Molecular Tests: Mutation scanning (30%), Dupl/del testing (10%)

Front 5

CHARGE SYNDROME

Back 5

MCA Syndrome
CHD7 gene; 8q12.1;
AD
Features: 4/7: eye Coloboma, Heart anomaly (conotruncal defects, arch abnormalities), choanal Atresia, growth and mental Retardation, Genitourinary malformations (microphallus), Ear anomalies (ossicular malformations, Mondini defect of the cochlea) and/or deafness. Facial palsy, cleft palate, TE fistula, and dysphagia are commonly associated. 20-25% mortality in the first year
Molecular Tests: CHD7 sequencing (60-65%)
Disease Mechanism: HAPLOINSUFFICIENCY (non-, mis-, del)

Front 6

COFFIN-LOWRY SYNDROME

Back 6

MCA Syndrome
RPS6KA3 gene; Xp22.2-p22.1; 70-80% new mutation
X-Linked Dominant
Features: ID, SS, Drop ep., kyphoscoliosis
severe to profound ID 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, normal to profound ID in females.

Front 7

CORNELIA DE LANGE SYNDROME: Type, Gene, Inheritance

Back 7

MCA Syndrome
NIPBL, SMC1L1
AD, XLR

Front 8

CRI DU CHAT

Back 8

MCA Syndrome (5p- Syndrome)
RPS14?, microRNA 145 and 146a?; 5p15.2
85% sporadic de novo deletions (80% are on the paternal chromosome); 12% unequal seg. of translocation or recombination of pericentric inversion in one parent,
Features: Cat-like cry (abnormal laryngeal development), slow growth, microcephaly, ID, hypotonia, strabismus, characteristic facial features.

Front 9

FRYNS SYNDROME

Back 9

MCA Syndrome
gene and chromosome UNKOWN
AR
Features:LGA, coarse face, CL/CP, diaphragmatic defect, distal digital hypoplasia, ID in survivors, agenesis of the CC, optic and olfactory tract
hypoplasia, GU malformation
Clin Test: symptomatic
Mol Test: none
most stillborn/early death. 14% live

Front 10

GREIG CEPHALOPOLYSYNDACTYLY

Back 10

MCA Syndrome
GLI3 gene; 7p13; (Zinc finger protein GLI3)
Inheritance: AD
Major findings: macrocephaly, ocular hypertelorism, preaxial polydactyly, cutaneous syndactyly. Developmental delay, ID, or seizures (<10%)- more common in those with large (>300 kb) dele including GLI3. Allelic with Pallister-Hall syndrome (caused by GLI3 frame shifting mutations).
Clinical Tests: 500-600 band karyotype 7p13 translocation or interstitial deletion (5-10%)
Molecular Tests: GLI3 sequence analysis (70%)
HAPLOINSUFFICIENCY

Front 11

JOUBERT SYNDROME

Back 11

MCA Syndrome
NPHP1, AHI1, CEP290, TMEM67; 2q13, 6q23.3, 12q21.32, 8q21.1-q22.1
AR
Features: Hypotonia infancy/ataxia later, DD/ID, alt 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.

Front 12

KABUKI SYNDROME

Back 12

MCA Syndrome
MLL2 (66%); 12q12-q14
AD
Features: long palpebral fissure, short nasal septum, fetal finger pads, malf. prominent ears, arched brows, IQ<80, depressed nasal tip, joint laxity, high palate, hypotonia, short stature, ptosis, CHD, CL/P, scoliosis, renal anomalies, hearing loss, speech delay
Clin Test: echocard., renal US, eye,neuropsychological testing
Molecular Tests: MLL2 gene sequencing

Front 13

MONOSOMY 1p36

Back 13

MCA Syndrome
unknown gene
Features: The most common terminal del syndrome. Hypotonia, dev delay, growth retardation, obesity, microcephaly, orofacial clefting, typical facial features. Minor cardiac malf, cardiomyopathy, seizures, ventricular dilation, SNHL
Clinical Tests: Brain CT/MRI
Molecular Tests: HR karyotype, confirmatory FISH us. needed. The majority are maternally derived.
Disease Mechanism: contiguous gene deletion syndrome

Front 14

PRADER WILI SYNDROME

Back 14

MCA Syndrome
Pat. exp'd. genes in imprinted locus on 15q11-13 (SNURF-SNRPN, MKRN3, MAGEL2, and NDN )
Aut: expressed from paternal 15
Features: Hypothalamic insufficiency, neonatal hypotonia, developmental delay, hyperphagia leading to obesity, short stature, small hands and feet, hypogonadism, ID
Molecular Tests: 3-5 Mb deletion of 15q11.2-q13 (~70%), matUPD (15%), PWS imprinting center defect (1-2%)

Front 15

RUBENSTEIN-TAYBI SYNDROME

Back 15

MCA Syndrome
CREBBP, EP300 genes; 16p13.3, 22q13
AD--but only few cases of affected parent & child
Features: microcephaly, beaked nose, broad thumbs and toes, cryptorchidism, growth delay, severe ID (35-50), CHD, strabismus, ptosis, sleep apnea, tumors (meningioma, pilomatrixoma, leukemia), behavior problems
Clinical Tests: ERG, echocardiogram, deletion or translocation occasionally seen on karyotype
Molecular Tests: FISH CREBBP (~10%), direct sequencing CREBBP (40-60%), EP300 (~3%)

Front 16

SMITH-MAGENIS SYNDROME

Back 16

MCA Syndrome
RAI1 gene; 17p11.2
AD (sporadic unless parental balanced translocation)
Features: mild-mod infantile hypotonia, feeding problems and FTT, short stature, brachydactyly, eye and ORL abnormalities, early speech delay with or w/out loss, peripheral neuropathy, sleep problems, and stereotypic bad behavior (self- injurious behaviors, inattention+hyperactivity, impulsivity, disobedience, the “self-hug” and “lick and flip” page turning motion), mild-mod ID, coarsening face over time
Clinical Tests: Renal US, echo, spine x-ray, FISH for 17p11.2 deletion (~90%)
Molecular Tests: RAI1 sequencing (5-10%
?Transcriptioinal Regulation?

Front 17

TRIPLOIDY

Back 17

MCA Syndrome
69,XXY>69,XXX (69,XYY very rare)
Sporadic without inc risk of recurrence
Features: >99% lost in first trimester, accounts for 6-10% of all SAb’s and 16-20% of all chrom ab SAb’s. Dysplastic calvaria with large posterior fontanelle, 3⁄4 finger syndactyly, ASD, VSD, hydrocephalus, holoprosencephaly.
Parent of origin effect: If Mat: small placenta, severe asymmetric IUGR with a large head
If Pat: hydropic large placenta, well grown to mod symmetric IUGR, nl or microcephalic head
Clinical Tests: Prenatal US, maternal serum hCG low
Molecular Tests: Karyotype

Front 18

TRISOMY 13, PATAU

Back 18

MCA Syndrome
80% sporadic, 20% due to translocation
Features: rarest live born trisomy disorder. Holoprosencephaly, polydactyly, seizures, HL, microcephaly, midline CL/P, omphalocele, cardiac and renal anomalies, ID. Mosaic Tri 13: very broad phenotype from typical features of full trisomy to more mild ID and physical features and longer survival.
Clinical Tests: Brain MRI, EEG, audiogram, echo, renal US Molecular Tests: Karyotype is diagnostic
75% are due to maternal nondysjunction, 20% to a translocation, and 5% to mosaicism.

Front 19

TRISOMY 18, EDWARD

Back 19

MCA Syndrome
Less than 1% due to a translocation
Features: clenched hand, fingers 2/5 overlap 3⁄4, IUGR, rocker bottom feet, micrognathia, prominent occiput, microphthalmia, VSD, ASD, PDA, generalized muscle spasm, renal anomalies, ID. Mosaic Tri 18 has variable but usually somewhat milder expression.
Clinical Tests: Echo, abdominal US.
Mat serum screen: low AFP, hCG, and UE3.
Molecular Tests: karytype is diagnostic
Disease Mechanism: Maternal nondysjunction (90%), mosaicism (10%)

Front 20

TRISOMY 21, DOWN

Back 20

MCA Syndrome
95% de novo, 5% due to Robertsonian translocation or isochromosome 21
Features: mild-mod ID, hypotonia, growth delay, strabismus, adult cataracts, myopia, conductive HL, macroglossia, hypodontia, joint hyperflexibility, hypogenitalism, congenital heart defect, duodenal atresia, hirschprung, thyroid disease, early onset Alzheimers, transient myeloproliferation, ALL
Clinical Tests: prenatal US abnormalities in 50%,
Mat serum screen: high free beta HCG, low PAPP-A.
Molecular Tests: Karyotype is diagnostic
Disease Mechanism: 90% due to maternal meiosis nondisjunction (3⁄4 MI error, 1⁄4 MII error)

Front 21

VACTERL/VATER ASSOCIATION

Back 21

MCA Syndrome
gene unknown
Features: Vertebral anomalies, Anal atresia, Cardiac mal. (VSD, PDA, TOF, TOV), Tracheoesophageal fistula, Esophageal atresia, Renal anomalies, and Limb anomalies (polydactyly, humeral hypoplasia, radial aplasia, proximally placed thumb). DX requires 3 of 7 features and it is a diagnosis of exclusion. A variant is VACTERL with hydrocephalus which can be AR or XL.
Clinical Tests: echo, spinal x-ray, limb x-ray, and renal US
Molecular Tests: None, but r/o aneuploidy with karyotype, Fanconi anemia with DEB testing, and consider SALL1 sequencing to rule out Townes-Brocks syndrome.
Disease Mechanism: unknown

Front 22

WOLF-HIRSCHORN SYNDROME
(4p-, monosomy 4p)

Back 22

MCA Syndrome
4p deletion, critical region includes two genes, WHSC1 and WHSC2 of unknown significance
87% de novo, 13% due to unbalanced translocation from a balanced parent
Features: “greek warrior helmet appearance”, microcephaly, pre and postnatal growth deficiency, ID variable, seizures, facial asymmetry, ptosis, IgA deficiency, structural brain anomalies, CL/P, CHD (ASD>PVS>VSD>PDA>AI>TOF), renal US
Clinical Tests: Distinctive EEG, Brain MRI, echo, plasma IgA level Molecular Tests: HR karyotype for 4p16.3 deletion (60-70%), FISH/array CGH for critical region deletion (>95%)

Front 23

HIDROTIC ECTODERMAL DYSPLASIA

Back 23

Dermatologic Syndrome
GJB6 gene, 13q12
AD
Features: malformed, thickened, small nails; HYPOtrichosis (partial or total alopecia), palmoplantar hyperkeratosis, normal sweating and teeth.
Clinical Tests: None
Molecular Tests: Three GJB6 mutations (G11R, A88V, V37E) account for 100% of indentified mutant alleles

Front 24

HYPOHIDROTIC ECTODERMAL DYSPLASIA

Back 24

Dermatologic Syndrome
EDA, EDAR, EDARADD genes; Xq12-q13.1, 2q11-q13, 1q42.2-q43
XL (95%), AD or AR (5%); Xq, 2q, 1q
Features: @birth peeling skin, perioral hyper pigment
HYPO trichosis and hydrosis (sparse hair, no sweating)
HYPOdontia (only 5-7 teeth)
Clinical Tests: dental xray.
Molecular Tests: EDA sequencing (~95% XL HED), EDAR and EDARADD sequencing

Front 25

INCONTINENTIA PIGMENTI

Back 25

Dermatologic Syndrome
IKBKG (aka NEMO) gene; Xq28
XLD (most male fetuses die)
Features: Major: Four stages of skin changes: erythema->blister->hyperpigmented streaks->atrophic skin patches. Minor: HYPO/andontia, alopecia, woolly hair, nail ridging or pitting, retinal neovascularization causing retinal detachment. ID is rare.
Molecular Tests: Southern blot: Exon 4-10 deletion (80%). Skewed X inactivation in females (not diagnostic).

Front 26

OCULOCUTANEOUS ALBINISM

Back 26

Dermatologic Syndrome
TYR and OCA2 genes; 11q14-q21, 15q11.2-q12
AR
Features:
OCA1A (no melanin synthesis) nystagmus, dec iris pigment, foveal hypoplasia, dec visual acuity, strabismus, white hair and skin, translucent iris. OCA1B (some melanin synthesis) milder eye and skin manifestation than OCA1.
OCA2 ocular problems same as OCA1 but better vision, range of skin and eye pigmentation from minimal to near normal
Molecular Tests: TYR sequencing (OCA1A: 2 mutations 83%; OCA1B: 2 mutations 37%). 2kb OCA2 deletion testing (most of Sub- Saharin African heritage)

Front 27

AMYOTROPHIC LATERAL SCLEROSIS

Back 27

Neuromuscular Disorder
SOD1 gene; 21q22
(rare genes: SETX, VAPB, BSCL2, VCP, ALS2, SPG20)
AD (AR ALS2 and SPG20)
Features: UMN: hyperreflexia, extensor plantar response, inc muscle tone, and weakness.
LMN: weakness, muscle wasting, hyporeflexia, muscle cramps, and fasciculations. Fronto-temporal dementia

Front 28

CHARCOT-MARIE TOOTH SYNDROME

Back 28

Neuromuscular Disorder
CMT1: Abnormal myelin, AD, 50% of all CMT
CMT2: Axonopathy, AD, 20-40% of all CMT
CMT Interm: Combo myelinopathy & axonopathy, AD,
CMT 4: Either myelinopathy or axonopathy, AR
CMTX: Axonopathy w/ 2nd myelin changes, XLD, 10-20% of all CMT
Features: slowly progressive weakness and atrophy of distal muscles in the feet and/or hands beginning in the 1st- 3rd decade; hearing loss; pes cavus foot deformity, hip dysplasia.
Clinical Tests: nerve conduction studies, nerve biopsy
Molecular Tests: Gene sequencing

Front 29

DUCHENNE MUSCULAR DYSTROPHY: Type, Gene, Inheritance

Back 29

Neuromuscular Disorder
DMD gene; Xp21.2
XLR

Molecular Tests: Multiplex PCR: DMD gene deletion (65% DMD, 85% BMD). Southern or quantitative PCR for gene duplication (6% DMD), DMD sequencing for small del/ins or point mutations (30% DMD)

Front 30

BECKER MUSCULAR DYSTROPHY Features:

Back 30

Later onset, less severe, weakness of quadriceps may be only sign, activity induced cramping. Preservation of neck flexor muscles (unlike DMD).

Front 31

CORNELIA DE LANGE SYNDROME: Features

Back 31

re/postnatal growth retardation, low anterior hairline and synophrys, diaphragmatic hernia, upper limb anomalies, ptosis, nystagmus, mod-severe ID, Heart (pulm valve stenosis and/or VSD)

Front 32

CORNELIA DE LANGE SYNDROME: Testing, Disease Mechanism

Back 32

Clinical Tests: none are diagnostic
Molecular Tests: NIPBL sequencing (~50%), SMC1L1 sequencing (4%)
Disease Mechanism: Unknown,most muts are truncating, prob protein haploinsufficiency

Front 33

DUCHENNE MUSCULAR DYSTROPHY: Features

Back 33

Symptoms present before age 5, progressive symmetrical muscular weakness, proximal>distal, calf hypertrophy, dilated cardiomyopathy (DCM).

Front 34

DUCHENNE MUSCULAR DYSTROPHY: Tests

Back 34

Clinical Tests: CK 10x nl in DMD, 5x nl in BMD. Unreliable test for carrier females, tends to decrease with age.

Front 35

BECKER MUSCULAR DYSTROPHY: Type, Gene, Inheritance

Back 35

Neuromuscular Disorder
DMD gene; Xp21.2
XLR

Front 36

FRIEDREICH’’S ATAXIA
Gene, Chromosome, Inheritanc

Back 36

FRDA
Frataxin Protein
9q13 Inheritance
AR

Front 37

FRIEDREICH’’S ATAXIA
Clinical Features

Back 37

Progressive degeneration of the dorsal root ganglia, posterior columns, corticospinal tracts, and the dorsal spinocerebellar tracts of the spinal cord and cerebellum. There is progressive limb and gait ataxia before age 25 yrs, absent tendon reflexes in the lower extremities. Within 5 years of disease onset: dysarthria, arefelxia, pyrimidal weakness of the legs, extensor plantar responses and distal loss of joint position and vibration sense. Also, scoliosis, pes cavus, optic nerve atrophy, hypertrophic cardiomyopathy, DM or glucose intolerance

Front 38

FRIEDREICH’’S ATAXIA
Molecular Testing

Back 38

GAA triplet repeat expansion in FRDA intron 1 (96% homozygous)
Normal 5-33, premutation 34-65, and disease causing: 66- 1700 repeats.

Front 39

HEREDITARY NEUROPATHY WITH LIABILITY TO PRESSURE PALSIES
Gene, Chromosome, Inheritance

Back 39

PMP22
Protein: Peripheral myelin protein 22
17p11.2
AD Inheritance

Front 40

HEREDITARY NEUROPATHY WITH LIABILITY TO PRESSURE PALSIES
Clinical Features

Back 40

adult with recurrent focal pressure palsies, mild polyneuropathy,
absent ankle reflexes,
reduced DTRs,
mild-mod pes cavus deformity

Front 41

HEREDITARY NEUROPATHY WITH LIABILITY TO PRESSURE PALSIES
Molecular Tests

Back 41

PMP22 sequencing (20%),
1.5-Mb PMP22 deletion (80%)

Front 42

LIMB-GIRDLE MUSCULAR DYSTROPHY (LGMD)
Gene, Chromosome, Inheritance

Back 42

CAPN3 (Calpain 3, 15q15.1-q21.1),
FKRP (Fukutin related protein, 19q13.1),
LMNA (Lamin-A/C, 1q21.2),
SGCA (alpha sarcoglycan, 17q12),
SGCB beta sarcoglycan, 4q12),
SGCD (delta-sarcoglycan, 5q33),
SGCG (gamma-sarcoglycan, 13q12),
DYSF (Dysferlin, 2p13.3)
Inheritance: most AR, some rare AD subtypes

Front 43

LIMB-GIRDLE MUSCULAR DYSTROPHY (LGMD)
Clincial Features

Back 43

AR Sarcoglycan LGMD: proximal limb weakness, difficulty running and walking, calf hypertrophy, onset age 3-15 (68% of childhood onset, 10% adult onset)

Calpain AR LGMD proximal limb weakness, difficulty running and walking, calf atrophy, onset 2-40 yrs (10-30% AR LGMD).

Dysferlin AR LGMD problems running and walking, foot drop, distal and/or pelvic weakness, transient calf hypertrophy, onset 17-23 yrs

Front 44

LIMB-GIRDLE MUSCULAR DYSTROPHY (LGMD)
Molecular Tests

Back 44

Gene sequencing (80-99%)

Front 45

MYOTONIC DYSTROPHY TYPE 1
Gene, Chromosome, Inheritance

Back 45

DMPK
Protein: Myotonin-protein kinase
Cytogenetic locus: 19q13.32
Inheritance: AD

Front 46

MYOTONIC DYSTROPHY TYPE 1
Clinical Features

Back 46

Multisystem disorder of skeletal and smooth muscle, eyes, heart, endocrine system, and CNS. MILD cataract and mild myotonia (50-150 repeats)

Classic muscle weakness and wasting, myotonia, cataract, and arrhythmia (100-1000 repeats).

Have grip myotonia (sustained muscle contraction leads to inability to quickly release a hand grip)
Congenital hypotonia and severe generalized weakness at birth often with resp. insufficiency and early death, MR is common (>2000 repeats)

Front 47

MYOTONIC DYSTROPHY TYPE 1
Molecular Tests

Back 47

CTG triplet repeat at the 3’-UTR of the DMPK (100%).

PCR: detect repeats up to ~100, southern blot (detect repeats>100)

Front 48

NEMALIN MYOPATHY
Gene, Chromosome, Inheritance

Back 48

ACTA1 (Actin, alpha skeletal muscle, 1q42.1), NEB (Nebulin, 2q22), TNNT1 (Troponin T, slow skeletal muscle, 19q13.4), TPM2 (Tropomyosin beta chain, 9p13.2-p13.1), TPM3 (Tropomyosin alpha-3 chain, 1q22-q23)
Inheritance: AR or AD

Front 49

NEMALIN MYOPATHY
Clinical Features

Back 49

weakness, hypotonia, and depressed or absent DTR’s. Weakness is usually most severe in the face, neck flexors, and proximal limb muscles. Age of onset: congenital, childhood, or adulthood.

Front 50

NEMALIN MYOPATHY
Molecular Testing

Back 50

ACTA sequencing: 15-25% of NM, ACTA Del/dup analysis: Exon 55.

Front 51

SPINAL MUSCULAR ATROPHY
Gene, Chromosome, Inheritance

Back 51

SMN1, SMN2
Proteins: survival motor neuron protein 1 and 2
5q12.2-q13.3
AR

Front 52

SPINAL MUSCULAR ATROPHY
Clinical Features

Back 52

arthrogryposis multiplex congenita, peripheral nerve hypomyelination. SMA I onset 0-6mo, muscle weakness, tongue fasiculations, absent DTRs SMA II muscle weakness onset after 6 months, finger trembling, low tone, absent DTRs, SMA III Weakness leads to frequent falls or trouble with stairs, onset 2-3yrs, proximal weakness (legs>arms), SMA IV adult onset

Front 53

SPINAL MUSCULAR ATROPHY
Molecular Testing

Back 53

Targeted mutation analysis: deletion of SMN1 exon 7 deletion (95-98%), SMN1 sequencing (2-5%). Carriers who have two copies of SMN1 in cis (~4% of the population) will be misdiagnosed as non-carriers. SMN2 copy # modifies the severity. 2 copies SMN2- SMA I, 3 copies- SMA II, 4-8 copies- SMA III. Absence of both SMN genes: lethal

Front 54

SYNDROMIC CONGENITAL MUSCULAR DYSTROPHY
(Fukuyama (FCMD), Muscle-Eye-Brain (MEB), Walker-Warburg (WWS), Congenital Muscular Dystrophy Type 1D (MDC1D)

Gene, Chromosome, Inheritance

Back 54

FCMD; FCMD (Fukutin, 9q31); MEB: POMGNT1 (protein O-mannosidase beta-1,2-N- acetylglucosaminyltransferase, 1p34-p33); WWS: POMT1 and POMT2 (Protein O-mannosyltransferase 1 and 2, 9q34.1, and 14q24.3); MDC1D (LARGE, glycosyltransferase-like protein LARGE, 22q12.3-q13.1 AUTOSOMAL RECESSIVE

Front 55

SYNDROMIC CONGENITAL MUSCULAR DYSTROPHY
Clinical Features

Back 55

Muscle weakness present at birth. Hypotonia and weakness.
Joint contracture (MEB and WWS: elbow, FMD: hip, knee, ankle elbow).

Front 56

SYNDROMIC CONGENITAL MUSCULAR DYSTROPHY
Molecular Tests

Back 56

none

Front 57

TAY SACHS
Gene, Chromosome, Inheritance

Back 57

HEXA
Protein: Hexosaminidase A
15q23-q24
Inheritance: AR

Front 58

TAY SACHS
Clinical Features

Back 58

Infantile weakness starts at 6 mo, exaggerated startle, seizures and vision loss by the end of the first year, neurodegeneration continues- deaf, cannot swallow, weakening of muscles, and eventual paralysis, death in toddler years. Juvenile muscle coordination problems, seizures, and vision problems starting as young children. Chronic and adult onset start later, progress more slowly, more rare.

Front 59

TAY SACHS
Molecular Testing

Back 59

Follow enzyme testing with DNA testing (some with a positive enzyme assay have a pseudodeficiency allele that does not cause Tay Sachs).
HEXA 6 common mutation panel: 92% of Ashkenazi Jewish

Front 60

Aarskog Syndrome Features

Back 60

Features:
Hypertelorism,
shawl scrotum,
brachydactyly,
short stature,
cryptorchidism,
cervical vertebral abnormalities,
Intel. Dis. (30%), milder manifestations in females

Front 61

Aarskog Syndrome
Clinical and Molecular Tests

Back 61

Clinical Tests: xray
Molecular Tests: FGD1 sequencing (7-20%)

Front 62

ANTLEY-BIXLER SYNDROME
FEATURES

Back 62

Features:
AMBIGUOUS GENITALIA, (enlarged cystic ovaries, poor masculinization in males), maternal virilization during pregnancy with an affected fetus.
CRANIOSYNOSTOSIS,
CHOANAL stenosis or atresia & stenotic external AUDITORY canals,
HYDROCEPHALUS.
Neonatal FRACTURES, bowing of the long bones, joint contracture,
RENAL malformations

Front 63

ANTLEY-BIXLER SYNDROME
CLINICAL TESTS
MOLECULAR TESTS

Back 63

Clinical Tests: Sterol or or steroid abnormalities using GC-MS, increased urinary pregnenolone and progesterone metabolites

Molecular Tests: POR sequence variants

Front 64

TOWNES-BROCKS SYNDROME
type, gene, chromosome, inheritance

Back 64

MCA
SALL1
16Q12.1
Autosomal Dominant

Front 65

Townes Brock Features

Back 65

Imperforate/Stenotic Anus
Thumb Abnormalities. BROAD THUMBS
Ear abnormalities/Hearing loss
Increased risk for heart and kidney defects
Extremely variable--poor penetrance for key features

Front 66

Williams Syndrome
Gene, chromosome, inheritance

Back 66

MCA
microdeletion at 7q11.23

Front 67

William Syndrome FEATURES

Back 67

Supravalvular aortic stenosis most common heart defect
5% have hypocalcemia
Typical Face: stellate irides, epicanthal folds, supraorbital edema, blue sclera, epicanhal folds, high set nose, large everted lower lip, small teeth
Short stature
mild-moderate MR
Hyper-acoustis, course voice
Extroverted personality