Syndromes: other Flashcards
Supervalvular aortic stenosis, pulmonic stenosis, hyperCa, friendly/anxious personality, stellate blue eyes, round cheeks, wide mouth
Williams syndrome, 7q11.23 deletion
HLHS/LV noncompaction, platelet dysfunction, immunodeficiency, ID, flat nasal root w/hypertelorism, down slanting PF, full brow
Jacobsen syndrome, 11q deletion
CHD (1/4 with LV noncompaction), structural brain abnormalities w/seizure and severe ID, deep-set eyes, straight eyebrows, thin upper lips, pointed nose
1p36 deletion syndrome
TOF/septal defects, distal pulmonary stenosis, arterial narrowing elsewhere, cholestasis/liver failure
Alagille syndrome: JAG1, NOTCH2
“Swiss cheese” atrial septum/common atrium, arrhythmia/heart block, radial ray defects
Holt-Oram syndrome: TBX5, SALL4
Complex CHD, immunodeficiency, ID, elongated eyes w/lateral eversion, long ears
Kabuki syndrome: XL, KMT2D, KDM6A
Double-outlet right ventricle, vision/hearing loss risk, GU m malformation, choanal atresia
CHARGE syndrome: CHD7
PS, HCM, or ASD, pectus, hypertelorism, down slanting PF, low-set ears, short stature
Noonan syndrome, AD RAS/MAPK
Novel treatment of RASopathies
MEK inhibitor - improves HCM, arrhythmia, lymphatic malformation; requires several years of treatment minimum
Most common genes causing familial hypertrophic cardiomyopathy
MYH7, MYBPC3 (40% each)
Most common genes causing familial hypertrophic cardiomyopathy
LMNA, MYH7 (up to 8%), TNNT2, SCN5A (up to 4%)
Most common genes causing ARVD/C
PKP2, DSG2, DSP, DSC2
Syndromes associated with cardiomyopathy
Rasopathies
BWS (HCM)
Chromosomal
Alstrom (DCM) - w/retinal dystrophy, hearing loss
Most common IEMs with CM
HCM: Pompe & Mito ~30%
DCM: 35% mito, 25% Barth, 10% carnitine def
Neuromuscular causes of CM
Friedrich’s ataxia, Duchenne/Becker MD
Aniridia gene
PAX6 (AD LOF aniridia, AR anophthalmia), WAGR (11p13 gene deletion + 2nd hit in WT1 loss)
Corneal clouding
MPS I, IV, VI, VII
Syndromes a/w cataracts
Galactosemia, Lowe, Fabry, myotonic dystrophy
Retinal dystrophy: onset in infancy vs after infancy
Leber congenital amaurosis (CRX AD, most AR incl RPE65 that has gene therapy) vs retinitis pigmentosa
Brain malformations (molar tooth sign, cerebellar vermis hypoplasia), hypotonia, cognitive impairment, congenital retinal dystrophy, polydactyl, renal anomalies
Joubert syndrome (AR, 25 genes)
Retinitis pigmentosa, hearing loss (aka deaf-blind), +/- poor balance (vestibular defects)
Usher syndrome, 9-10 genes “USH”
Polydactyly, obesity, cognitive defects, renal disease, post-axial polydactyly, hypogonadism, retinal dystrophy
Bardet-Biedl syndrome (AR, 22 genes; triallelic inheritance for a few)
Albinism, loss of fovea, oculuar vs oculocutaneous genes
Ocular OA1 (XL) vs Oculocutaneous OCA1 (tyrosinase) & OCA2 (P gene, deletion in AAs, hair/nevi darken over time)
Albinism + bleeding (platelet dysfunction), pulmonary fibrosis, granulomatous colitis
Hermansky-Pudlak: AR, absence of platelet dense bodies, HPS genes 1-8
Albinism + ID
Angelman/PWS (<1% w/OCA2 loss)
“Albinism” (silvery hair) + immunodeficiency (superficial pyoderma), late onset ataxia, peripheral neuropathy, accelerated phase–>HLH
Chediak-Higashi: AR, LYST1 (lysosomal trafficking regulator); affects multiple granules incl neutrophils, platelets, melanin
Optic nerve hypoplasia, pituitary hypoplasia, midline forebrain defects (absent septum pellucid or corpus callosum)
Septo-optic dysplasia, mostly sporadic
Epidermolysis bullosa simplex, heals without scarring
AD mutations in keratins
Junctional epidermolysis bullosa, atrophic scarring
Laminin 332 or collagen XVII/BPAg2 (hemidesmosome)
Dystrophic epidermolysis bullosa, diffuse & deforming (especially AR form)
AD form Collagen VII (anchoring DEJ); AR more severe, a/w anemia, DCM, SCC
Variable bullae, photosensitivity, cutaneous atrophy, poikiloderma, pseudosyndactyly, erosion of mucosa, increased SCC risk
Kindler syndrome: FERMT1/KIND1 (integrin signaling)
Linear blistering + pigmentary changes seizures, ID, microcephaly cataracts, retinal detachment, pegged/missing teeth, alopecia, wiry hair, miscarriage
Incontinentia pigmenti: IFBKG aka NEMO (XD, male lethal)
4 stages of incontinentia pigment
Vesicular, verrucous, hyperpigmented, hypopigmented (no hair in areas)
Alopecia, no sweat, frontal bossing, saddle nose, everted lips, hypodontia
Hypohidrotic ectodermal dysplasia: most commonly XR w/ectodysplasin A
No sweat, hypotrichosis, seborrheic/atopic dermatitis, hypogammaglobulinemia, impaired B cell switch, hyperIgM
Hypohidrotic ectodermal dysplasia w/immunodeficiency, XR hypomorphic mutation in IKBKG/NEMO (often in sons of moms with IP)
Hypotrichosis, brittle/sparse hair, dystrophic fingernails, palmar hyperkeratosis; normal teeth & eccrine glands
Hidrotic ectodermal dysplasia: AD, GJB6 (connexion 30)
Hypodontia w/cone-shaped teeth, brittle spooned nails
Witkop tooth & nail: AD, MSX1 (TF)
Congenital lipomatous overgrowth, vascular malformation, epidermal nevi (wart-like), and spinal/skeletal anomalies incl sandal gap
CLOVES: PIK3CA overgrowth
Megalencephaly (often w/brain structural Abel), capillary malformation esp. upper lip, frontal bossing, syndactyly, polydactyly, hemihypertrophy
Megalencephaly-Capillary malformation, PIK3CA overgrowth
Congenital hearing loss w/enlarged vestibular aqueducts, late-onset goiter/hypothyroid
Pendred syndrome: SCL26A4 (DFNB4)
Congenital hearing loss, long QT syndrome
Jervell & Lange-Nielsen syndrome (KCNQ1, KCNE1)
Variable onset progressive hearing loss, ovarian dysgenesis, neurological impairment
Perrault syndrome (6 genes)
Most common 2 genes for nonsyndromic hearing loss
GJB2, STRC (stereocillin)
White forelock w/early gray hair and hypoplastic blue irides/heterochromia, high wide nasal root, hearing loss
Waardenberg type 1
