Syndromes: other

Question 1

Supervalvular aortic stenosis, pulmonic stenosis, hyperCa, friendly/anxious personality, stellate blue eyes, round cheeks, wide mouth

Answer 1

Williams syndrome, 7q11.23 deletion

Question 2

HLHS/LV noncompaction, platelet dysfunction, immunodeficiency, ID, flat nasal root w/hypertelorism, down slanting PF, full brow

Answer 2

Jacobsen syndrome, 11q deletion

Question 3

CHD (1/4 with LV noncompaction), structural brain abnormalities w/seizure and severe ID, deep-set eyes, straight eyebrows, thin upper lips, pointed nose

Answer 3

1p36 deletion syndrome

Question 4

TOF/septal defects, distal pulmonary stenosis, arterial narrowing elsewhere, cholestasis/liver failure

Answer 4

Alagille syndrome: JAG1, NOTCH2

Question 5

“Swiss cheese” atrial septum/common atrium, arrhythmia/heart block, radial ray defects

Answer 5

Holt-Oram syndrome: TBX5, SALL4

Question 6

Complex CHD, immunodeficiency, ID, elongated eyes w/lateral eversion, long ears

Answer 6

Kabuki syndrome: XL, KMT2D, KDM6A

Question 7

Double-outlet right ventricle, vision/hearing loss risk, GU m malformation, choanal atresia

Answer 7

CHARGE syndrome: CHD7

Question 8

PS, HCM, or ASD, pectus, hypertelorism, down slanting PF, low-set ears, short stature

Answer 8

Noonan syndrome, AD RAS/MAPK

Question 9

Novel treatment of RASopathies

Answer 9

MEK inhibitor - improves HCM, arrhythmia, lymphatic malformation; requires several years of treatment minimum

Question 10

Most common genes causing familial hypertrophic cardiomyopathy

Answer 10

MYH7, MYBPC3 (40% each)

Question 11

Most common genes causing familial hypertrophic cardiomyopathy

Answer 11

LMNA, MYH7 (up to 8%), TNNT2, SCN5A (up to 4%)

Question 12

Most common genes causing ARVD/C

Answer 12

PKP2, DSG2, DSP, DSC2

Question 13

Syndromes associated with cardiomyopathy

Answer 13

Rasopathies
BWS (HCM)
Chromosomal
Alstrom (DCM) - w/retinal dystrophy, hearing loss

Question 14

Most common IEMs with CM

Answer 14

HCM: Pompe & Mito ~30%
DCM: 35% mito, 25% Barth, 10% carnitine def

Question 15

Neuromuscular causes of CM

Answer 15

Friedrich’s ataxia, Duchenne/Becker MD

Question 16

Aniridia gene

Answer 16

PAX6 (AD LOF aniridia, AR anophthalmia), WAGR (11p13 gene deletion + 2nd hit in WT1 loss)

Question 17

Corneal clouding

Answer 17

MPS I, IV, VI, VII

Question 18

Syndromes a/w cataracts

Answer 18

Galactosemia, Lowe, Fabry, myotonic dystrophy

Question 19

Retinal dystrophy: onset in infancy vs after infancy

Answer 19

Leber congenital amaurosis (CRX AD, most AR incl RPE65 that has gene therapy) vs retinitis pigmentosa

Question 20

Brain malformations (molar tooth sign, cerebellar vermis hypoplasia), hypotonia, cognitive impairment, congenital retinal dystrophy, polydactyl, renal anomalies

Answer 20

Joubert syndrome (AR, 25 genes)

Question 21

Retinitis pigmentosa, hearing loss (aka deaf-blind), +/- poor balance (vestibular defects)

Answer 21

Usher syndrome, 9-10 genes “USH”

Question 22

Polydactyly, obesity, cognitive defects, renal disease, post-axial polydactyly, hypogonadism, retinal dystrophy

Answer 22

Bardet-Biedl syndrome (AR, 22 genes; triallelic inheritance for a few)

Question 23

Albinism, loss of fovea, oculuar vs oculocutaneous genes

Answer 23

Ocular OA1 (XL) vs Oculocutaneous OCA1 (tyrosinase) & OCA2 (P gene, deletion in AAs, hair/nevi darken over time)

Question 24

Albinism + bleeding (platelet dysfunction), pulmonary fibrosis, granulomatous colitis

Answer 24

Hermansky-Pudlak: AR, absence of platelet dense bodies, HPS genes 1-8

Question 25

Albinism + ID

Answer 25

Angelman/PWS (<1% w/OCA2 loss)

Question 26

"Albinism" (silvery hair) + immunodeficiency (superficial pyoderma), late onset ataxia, peripheral neuropathy, accelerated phase-->HLH

Answer 26

Chediak-Higashi: AR, LYST1 (lysosomal trafficking regulator); affects multiple granules incl neutrophils, platelets, melanin

Question 27

Optic nerve hypoplasia, pituitary hypoplasia, midline forebrain defects (absent septum pellucid or corpus callosum)

Answer 27

Septo-optic dysplasia, mostly sporadic

Question 28

Epidermolysis bullosa simplex, heals without scarring

Answer 28

AD mutations in keratins

Question 29

Junctional epidermolysis bullosa, atrophic scarring

Answer 29

Laminin 332 or collagen XVII/BPAg2 (hemidesmosome)

Question 30

Dystrophic epidermolysis bullosa, diffuse & deforming (especially AR form)

Answer 30

AD form Collagen VII (anchoring DEJ); AR more severe, a/w anemia, DCM, SCC

Question 31

Variable bullae, photosensitivity, cutaneous atrophy, poikiloderma, pseudosyndactyly, erosion of mucosa, increased SCC risk

Answer 31

Kindler syndrome: FERMT1/KIND1 (integrin signaling)

Question 32

Linear blistering + pigmentary changes seizures, ID, microcephaly cataracts, retinal detachment, pegged/missing teeth, alopecia, wiry hair, miscarriage

Answer 32

Incontinentia pigmenti: IFBKG aka NEMO (XD, male lethal)

Question 33

4 stages of incontinentia pigment

Answer 33

Vesicular, verrucous, hyperpigmented, hypopigmented (no hair in areas)

Question 34

Alopecia, no sweat, frontal bossing, saddle nose, everted lips, hypodontia

Answer 34

Hypohidrotic ectodermal dysplasia: most commonly XR w/ectodysplasin A

Question 35

No sweat, hypotrichosis, seborrheic/atopic dermatitis, hypogammaglobulinemia, impaired B cell switch, hyperIgM

Answer 35

Hypohidrotic ectodermal dysplasia w/immunodeficiency, XR hypomorphic mutation in IKBKG/NEMO (often in sons of moms with IP)

Question 36

Hypotrichosis, brittle/sparse hair, dystrophic fingernails, palmar hyperkeratosis; normal teeth & eccrine glands

Answer 36

Hidrotic ectodermal dysplasia: AD, GJB6 (connexion 30)

Question 37

Hypodontia w/cone-shaped teeth, brittle spooned nails

Answer 37

Witkop tooth & nail: AD, MSX1 (TF)

Question 38

Congenital lipomatous overgrowth, vascular malformation, epidermal nevi (wart-like), and spinal/skeletal anomalies incl sandal gap

Answer 38

CLOVES: PIK3CA overgrowth

Question 39

Megalencephaly (often w/brain structural Abel), capillary malformation esp. upper lip, frontal bossing, syndactyly, polydactyly, hemihypertrophy

Answer 39

Megalencephaly-Capillary malformation, PIK3CA overgrowth

Question 40

Congenital hearing loss w/enlarged vestibular aqueducts, late-onset goiter/hypothyroid

Answer 40

Pendred syndrome: SCL26A4 (DFNB4)

Question 41

Congenital hearing loss, long QT syndrome

Answer 41

Jervell & Lange-Nielsen syndrome (KCNQ1, KCNE1)

Question 42

Variable onset progressive hearing loss, ovarian dysgenesis, neurological impairment

Answer 42

Perrault syndrome (6 genes)

Question 43

Most common 2 genes for nonsyndromic hearing loss

Answer 43

GJB2, STRC (stereocillin)

Question 44

White forelock w/early gray hair and hypoplastic blue irides/heterochromia, high wide nasal root, hearing loss

Answer 44

Waardenberg type 1