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155 Cards in this Set
- Front
- Back
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21-hydroxylase deficient CAH |
- virilized female/childhood virilization in males - precocious puberty - infant w/ salt-wasting crisis at birth - CYP21A2 (AR) |
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22q11.2 deletion aka DiGeorge syndrome aka Velocardiofacial syndrome (VCF) |
- congenital heart defects (conotruncal, TOF) - thymic hypoplasia/immune dysfunction - CP/palate dysfunction - hypocalcemia - renal anomalies - increased risk for psychiatric disorders (30%) |
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Aarskog syndrome |
- hypertelorism - shawl scrotum/cryptorchidism - brachydactyly - short stature - cervical vertebral abnormalities - FGD1 gene (XLR, some AR, AD cases reported) |
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Achondroplasia |
- short stature - rhizomelic shortening - trident hand - frontal bossing/midface hypoplasia - macrocephaly - spinal cord compression - FGFR3 (AD, 80% de novo) |
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Acute Intermittent Porphyria |
- abdominal pain - muscle weakness - neuropathy - hysteria/anxiety - hepatocellular carcinoma - acute attacks; onset after puberty - HMBS gene (AD) |
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Addison's |
- inadequate glucocorticoid production, leading to ineffective use of lipid reserves - weight loss - weakness - lowered blood glucose - pigment changes from melanocyte stimulation - multifactorial - many ppl or family members have another autoimmune disorder (commonly DMT1) |
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Alagille |
Dx is bile duct paucity on liver bx AND any three: - cardiac defects (PA, TOF) - cholestasis - skeletal abnormalities (butterfly vertebrae) - eye - characteristic facial features - developmental delay - JAG2/NOTCH2 genes (AD, 50-70% de novo) |
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Alpha Thalassemia |
- inherited anemia - varying degrees of severity from asymptomatic to lethal, depending on carrier status - HBA1/HBA2 (AR) |
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Alpha-1 Antritrypsin Deficiency |
- Adult COPD - childhood/adult liver disease - age of onset: 40-50y if smoker, 60s if not - SERPINA1 (AR) |
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Alpert syndrome and Thin BM Nephropathy |
- spectrum from progressive renal disease with cochlear and ocular abnormalities to isolated hematuria with benign course - 80-90% have SN deafness by age 40 in males, later in females - COL4A5/COL4A3/COL4A4 (XL: 80%, AR: 15%, AD: 5%) |
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Amyotrophic Lateral Sclerosis (ALS) aka Lou Gehrig's disease |
- hyperreflexia - muscle cramps/wasting - frontotemporal dementia - weakness - increased muscle tone - SOD1 mostly (AD, rarely AR) |
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Androgen Insensitivity syndrome |
- evidence of feminization of external genitalia - abnormal secondary sex development - infertility in those with 46,XY karyotype - complete: typical female genitalia - partial: predominately female or male, or ambiguous - mild: normal male genitalia - AR (XLR) |
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Angelman syndrome |
- severe DD/MR - severe speech impairment - gait ataxia and/or limb tremors - inappropriate demeanor that includes laughing - microcephaly/seizures - 4-6Mb del (65-75%); UBE3A mutation (11%); imprinting defect (2.5%); unbalanced translocation (<1%); pat UPD (<1%); deletion of imprinting center (0.5%) |
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Ankylosing Spondylitis |
- stiffening and fusion of spine - inflammation where ligaments, tendons, and joint capsule join bone - more common in men - strongly associated with HLA type B27 - multifactorial (assoc w/ ERAP1, IL1A, IL23R) |
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Antley-Bixler syndrome |
- ambiguous genitalia/enlarged cystic ovaries - poor masculinization in males - maternal virilization during pregnancy w/ an affected fetus - craniosynostosis - choanal stenosis/atresia - stenotic external auditory canals - hydrocephalus - renal malformations - POR gene (AR) |
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Ataxia Telangiectasia |
- progressive celebellar ataxia (onset 1-4y) - oculomotor apraxia - conjuctival telangiectasia - immunodeficiency/frequent infections - sensitive to ionizing radiation - cancer risk (lymphoma/leukemia) - gonadal dysfunction - ATM (AR); carriers at increased risk for cancer |
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Ataxia w/ Oculomotor Apraxia Types 1 & 2 |
- childhood onset of slowly progressive cerebellar ataxia, followed by oculomotor apraxia and a severe primary motor peripheral axonal motor neuropathy - oculomotor apraxia progresses to external ophtalmoplegia - APTX/SETX (AR) |
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Bardet-Biedl syndrome |
- cone-rod dystrophy - truncal obesity - postaxial polydactyly - cognitive impairment - male hypogonadotropic hypogonadism - renal dysfunction - legally blind by 15y - majority have significant learning difficulties - BBS1/BBS10 (AR; 10% could be triallelic) |
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Bare Lymphocyte syndrome |
- lymphocytes and macrophages unable to process MHC proteins - 3 types depending on what's missing: MHC-1, MHC-2, or both - FTT, numerous infections - antigen presentation doesn't occur correctly - RFX5/RFXAP/MHC2TA/RFXANK (AR); TAP2/TAP1/TAPBP (AR) |
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Beckwith-Wiedemann syndrome |
- hemihypertrophy - macrosomia/macroglossia - visceromegaly - omphalocele - embryonal tumors - ear creases/pits - renal abnormalities - 20% mortality - CDKN1C/H19/KCNQ10T1 (AD - 15%) |
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Beta Thalassemia |
- severe anemia - severe FTT and shortened life expect w/out tx - intermedia: presents later, milder anemia, rarely requires transfusion, risk for Fe overload - Pops at risk: Mediterranean, Middle Eastern, Indian, Thai, Chinese, AA, African - HBB (AR) |
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Blepharophimosis, Ptosis, and Epicanthus Inversus (BPES) |
- blepharophimosis - ptosis - epicanthal inversus - telecanthus - broad nasal bridge - low-set ears - short philtrum - FOXL2 (AD - 50% de novo) |
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Bloom syndrome |
- IUGR - hyper/hypopigmentation - butterfly distribution sun sensitive telangiectasia - microcephaly/normal intelligence - high-pitched voice - azoospermia/POF - increased cancer risk (variable type/site) - BLM (AR) - 1 in 100 AJ carrier freq
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Branchiootorenal syndrome |
- malformations of outer, middle, and inner ear assoc w/ conductive, SN, or mixed hearing impairment - branchial fistulae and cysts - renal malformations, variable - EYA1/SIX1 (AD) |
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BRCA1/BRCA2 |
- Breast - Ovarian - Prostate - Stomach - Colon - Melanoman - 3 common AJ mutations (AD) |
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Brugada syndrome |
- syncope - high risk for ventricular arrhythmias and sudden death - manifests primarily in adulthood (mean age of sudden death is 40y) - may present as SIDS - SCN5A (AD) |
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Bruton's Agammaglobulinemia |
- B-cells unable to mature/absent plasma cells - very low levels of immunoglobulins - recurrent bacterial infections, rudimentary tonsils and adenoids - BTK (XLR) |
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CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) |
- stroke-like episodes before age 60 - cognitive disturbance - behavioral abnormalities - migraine w/ aura - NOTCH3 (AD) |
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Canavan disease |
- macrocephaly/lack of head control - DD by age 3-5y - severe hypotonia evolving to spasticity - never sit, walk, or speak - ASPA (AR) - 3 commom muts accound for 99% of AJ alleles, and 50-55% of non-AJ alleles |
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CFTR-related disorders |
- chronic airway infection - chronic sinusitis - meconium ileus - malabsorption d/t pancreatic insufficiency - male infertility d/t azoospermia - progression to end-stage lung disease - CFTR (AR); delF508 = 30-80% of mut alleles |
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Charcot Marie Tooth disease |
phenotype: slow, progressive weakness/atrophy of distal muscles in feet/hands, hearing loss, hip dysplasia type 1 (AD) - 50%: abnl myelin (PMP22/MPZ/LITAF/EGR2/NEFL) type 2 (AD) - 20-40%: axonopathy (KIF1B/MFN2/RAB7/LMNA/GARS/NEFL/HSPB1/MPZ/GDAP) intermediate type (AD) - rare: combo of mylein and axonopathy (DNM2/YARS) type 4 (AR) - rare: either myelo- or axonopathy (GDAP1/MTMRL/CMT4B2/SH3TC2/NDRG1/EGR2/PRX) type X (XLD) - 10-20%: axonopathy with secondary myelin changes
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CHARGE |
4 out of 7: eye Coloboma Heart defect (conotruncal, arch abnormalities) choanal Atresia growth/mental Retardation Genitourinary malformations Ear anomalies &/or deafness - can also have facial palsy, CP, TE fistula, and dysphagia - 20-25% mortality in the first year - CHD7 (AD) |
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Cleidocranial dysostosis |
- delayed closure of the cranial sutures - hypoplastic or aplastic clavicles - multiple dental abnormalities - abnormally large wide open anterior fontanel - midface hypoplasia - brachydactyly - hearing loss - normal intellect - RUNX2 (AD w/ variable expressivity) |
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Cockayne syndrome |
type 1: normal prenatal growth, severe FTT in first 2y, progressive deterioration of vision, hearing, CNS, and peripheral nervous system type 2: growth failure at birth, little/no postnatal neuro devlpment, kyphosis/scoliosis, joint contracture type 3: normal growth & develpmt or late onset Xeroderma Pigmentosa variant: facial freckling, early skin cancer, MR, spasticity, short stature, hypogonadism ERCC6/ERCC8 (AR) |
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Coffin-Lowry syndrome |
- severe to profound MR in males; normal to profound MR in females - short, soft fleshy hands - tapering fingers with small terminal phalanges - males <3%tile in height - microcephaly - kyphosis RP56KA3 (XLD) |
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Complete Mole |
46,XX all paternal in origin - abnormal placenta - little/no fetus - looks like cluster of grapes - risk of choriocarcinoma - high hCG |
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Congenital Contractural Arachnodactyly aka Beals syndrome |
- Marfanoid appearance - long slender fingers/toes - crumpled ears - major joint contracture - muscle hypoplasia - kyphosis/scoliosis Severe/lethal: aortic dilation, ASD/VSD, duodenal/esophageal atresia, malrotation - FBN2 (AD) |
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Congenital Hearing Loss (Connexin 26 & 30) |
- congenital mild to profound SNHL - rare pts can have AD w/ skin findings - GJB2/GJB6 (AR) |
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Cornelia de Lange syndrome |
- pre- and postnatal growth retardation - low anterior hairline and synophyrs - diaphragmatic hernia - upper limb anomalies - ptosis/nystagmus - mod to severe MR - pulm valve stenosis or VSD - NIPBL/SMC1L1 (AD/XLR) |
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Cri-du-chat syndrome aka 5p- syndrome |
- cat-like cry - slow growth - microcephaly - MR - hypotonia - strabismus - characteristic facial appearance - 5p15.2 region (85% sporadic de novo - 80% are on paternal chrom) |
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Cushing's disease |
- lipid reserves redistributed - moonface appearance - weight gain around trunk/face - muscle weakness - progressively thin/brittle bones - weakened immune system - mood disorders - multifactorial; overproduction of glucocorticoids usually d/t hypersecretion of ACTH from benign tumors |
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Diastrophic dysplasia |
- limb shortening - normal-sized skull - hitchhiker thumbs - small chest - CP - cystic ear swelling - normal IQ - SLC26A2 (AR) |
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T21 |
- milt to mod MR - hypotonia - growth delay - strabismus - adult cataract/myopia - conductive HL - macroglossia/hypodontia - heart defect - ALL - duodenal atresia/Hirschsprung's |
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Duchenne & Becker muscular dystrophy |
more severe: sx < 5y, progressive symmetrical muscular weakness, calf hypertrophy, dilated cardiomyopathy more mild: later onset/less severe, weakness in quads may be only sign, activity-induced cramping, DCM can occur in isolation - DMD (XLR) |
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Dyskeratosis Congenita |
- bone marrow failure - nail dystrophy - leukoplakia - skin hyperpigmentation - cancer susceptibility - DKC1 (XL), TERT/TERC (AD), NHP2/NOF1O/T1NF2 (AR) |
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Early-onset familial Alzheimer's disease |
- onset < 60y - dementia - confusion - poor judgment - language disturbance - agitation/withdrawal/hallucination PSEN1/APP/PSEN2 (AD) |
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T18 |
- clenched hand - fingers 2/5 overlap 3/4 - IUGR - rocker bottom feet - micrognathia - VSD/ASD/PDA - renal anomalies - MR 10% mosaic |
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Ehlers-Danlos Classic (types 1 & 2) |
- skin hyperextensibility - widened atrophic scars - joint hypermobility - smooth velvety skin - molluscoid pseudotumors - aortic root dilation - COL5A1/COL5A2 (AD) |
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Ehlers-Danlos Hypermobility (type 3) |
- joint hypermobility - soft/velvety skin w/ normal or slightly increase elasticity - recurrent joint dislocation - easy bruising - high narrow palate - dental crowding TNXB (AD); molecular testing not done |
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Ehlers-Danlos Vascular (type 4) |
Major criteria: arterial/intestinal rupture, uterine rupture during preg, f/hx of vascular EDS Minor criteria: thin/translucent skin, easy bruising, thin lips/philtrum, gum recession, small chin/thin nose, large eyes, ages appearance of hands, small joint hypermobility, tendon/muscle rupture, vericose veins, CHD, club foot - COL3A1 (AD) |
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Ehlers-Danlos Kyphoscoliotic (type 6) |
Major: friable, hyperextensible skin, thin scars, easy bruising, generalized joint laxity, severe muscle hypotonia, progressive scoliosis, scleral fragility and rupture of the globe Minor: widened atrophic scars, marfanoid habitus, rupture of medium-sized arteries, mild to mod delay of gross motor milestones - PLOD1 (AR) |
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Epidermolysis Bullosum |
- group of disorders characterized by excessive blistering at minor injury or friction - sx vary widely - sever cases can involve widespread blistering, leading to infections, dehydration, and other medical problems - KRT5/KRT14/PLEC (AD) |
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Factor 5 Leiden |
loss of function = hemorrhage gain of function = thrombosis - activated by thrombin; inactivated by APC - mutation results in absence of APC - increased risk for DVT FS gene (AD = mod risk, AR = significant risk) - 3-8% of Euro pop heterozygotes |
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Familial Adenomatous Polyposis |
100-1000 polyps in childhood to adolescence - abnl desmoid tumors - jaw osteoma - absent/supernumerary/malformed teeth - hepatoblastoma - thyroid cancer - epidermoid cyst APT (AD, 15-30% de novo) Attenuated: fewer polyps, more proximal Gardner: colonic adenomatous polyps, osteomas, soft tissue tumors Turcot: colon cancer, CNS tumors (medulloblastoma) |
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Familial Dysautonomia |
- probs w/ digestion, breathing, regulation of BP/body temp, taste/pain perception, and thermoregulation - decreased life expectancy - IKBKAP (AR); affected individuals are almost exclusively AJ |
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Familial Mediterranean Fever |
type 1: recurrent febrile epilepsy w/ peritonitis, synovitis, or pleuritis, AA-type amyloidosis type 2: amyloidosis as first clinical presentation MEFV (AR) |
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Fanconi Anemia |
- short stature - abnl pigmentation - radial/GU/ear/heart/GI/CNS malformations - hearing loss - hypogonadism - DD - aplastic anemia - solid tumors - FANCA/B/C/D2/E/F/G/BRCA2/BRIP1/FANCL (AR) |
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FGFR-related craniosynostosis (Pfeiffer, Apert, Crouzon, Beare-Stevenson, Jackson-Weiss, Crouzon w/ acanthosis nigricans, Muenke) |
all but Muenke assoc w/ bicoronoal craniosynostosis or cloverleaf skull, distinctive facial features, and variable hand/foot anomalies - FGFR1 (Pfeiffer)/FGFR2 (Crouzon, Jackson-Weiss, Apert, Pfeiffer)/FGFR3 (Crouzon w/acanthosis nig, Muenke) |
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Fragile X syndrome |
- delayed motor/verbal development - MR (mod-sev in boys, milder in girls) - prominent jaw/forehead - autistic features Carriers can have POF/ataxia/anxiety and depression Carrier males: progressive intention tremor, ataxia/parkinsonism, autonomic dysfunction |
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Friedreich's Ataxia |
- progressive degeneration of dorsal root ganglia - progressive limb and gait ataxia <25y - absent tendon reflexes in lower extremities w/in 5y of disease onset: dysarthria, arefelxia, scoliosis, optic nerve atrophy, HCM - FRDA (AR) - GAA trinuc repeat (normal: 5-33, premut: 34-65, mut: 66-1700) |
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Fryns syndrome |
- LGA - coarse face - CL/CP - diaphragmatic hernia - distal digital hypoplasia - MR - agenesis of corpus callosum - GU malformation - majority are stillborn or die in early neonatal period; 14% survive AR, unknown genes |
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Gorlin syndrome aka Nevoid Basal Cell Carcinoma syndrome |
- basal cell carcinoma (very early onset) - multiple jaw keratocysts - defects in iris or lens/blindness - facial dysmorphism - palmar/plantar pits - PTCH1 (AD); component of SHH signalling pathway |
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Graves disease aka hyperthyroidism |
- palpitations - heat intolerance - insomnia - nervousness - weight loss - muscle weakness - staring gaze multifactorial; autoimmune disorder: overproduction of thyroid hormones (may also be result of adenomas of thyroid) |
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Greig Cephalopolysyndactyly (GCPS) |
Major: macrocephaly, ocular hypertelorism, preaxial polydactyly, cutaneous syndactyly Also: DD, MR, seizures (<10%) GLI3 (AD); frameshifting mutations cause Pallister-Hall syndrome |
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Harlequin Ichthyosis |
- infants born w/ hard thick skin covering most of their body - skin forms plates separated by deep fissures - limits movement and can restrict breathing - infants have trouble controlling water loss, temp, and ability to fight infection - rare for infants to survive newborn period - ABCA12 (AR) |
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Hemophilia A |
- hemarthrosis or intracranial bleed w/ mild to no trauma - deep muscle hematomas - prolonged/renewed bleeding after trauma/surgery - excessive bruising - prolonged PTT - F8 (XLR); 10% of carrier females have at least mild hemophilia |
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Hemophilia B |
- hemarthrosis or intracranial bleed w/ mild to no trauma - deep muscle hematomas - prolonged/renewed bleeding after trauma/surgery - prolonged PTT - F9 (XLR) |
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Hereditary Hemorrhagic Telangiectasia |
- nosebleeds - mucocutaneous telangiectasias (lips/oral cavity/fingers/nose) - visceral AV malformation (pulm/cerebral/hepatic/ spinal/GI) - direct connection between veins and arteries ACVRL1/ENG (AD) |
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Hereditary Neuropathy w/ Liability to Pressure Palsies |
- prolongation of distal nerve conduction latencies (virtually 100%) - normal general motor nerve conduction velocities PMP22 (AD) |
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Hereditary Nonpolyposis Colon Cancer aka Lynch syndrome |
Cancers: colon, endometrial, stomach, ovary, brain/CNS, urinary tract, small bowel Amsterdam II criteria: 3 or more affected family members, at least 1 who is a FDR of the other 2, 2 successive generations affected, 1 or more HNPCC cancer dx <50y, exclusion of FAP - MLH1/MSH2/MSH6/PMS2 (AD) - 80% lifetime risk for colorectal cancer |
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Hermansky-Pudlak syndrome |
- findings of oculocutaneous albinism and a bleeding diathesis - hypopigmentation of the skin/hair - nystagmus/reduced iris/retinal pigment - foveal hypoplasia - increased crossing of optic nerve fibers - can develop skin cancer, pulm fibrosis, colitis HPS1/AP3B1/HPS3/4/5/6/7/8 (AR) |
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HFE-associated hereditary hemochromatosis (HFE-HHC) |
- early sx: abdominal pain, weakness, lethargy, weight loss - high iron absorption by GI mucosa - excessive storage in liver, skin, pancreas, heart, joints, and testes HFE (AR) - low penetrance |
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Hidrotic Ectodermal Dysplasia |
- malformed, thickened, small nails - hypotrichosis - palmoplantar hypokeratosis - normal sweating and teeth GJB6 (AD); 3 muts account for 100% of ID'd mut alleles |
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Holt-Oran syndrome |
- 100% have carpal bone abnormality - 75% have CHD, most often multiple ASD/VSD, or arrhythmia including AV block TBX5 (AD), 85% de novo |
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Huntington disease |
- progressive motor disability involving both voluntary and involuntary movement - cognitive decline - psychiatric disturbances Mean age of onset: 35-44y HD (AD); trinuc expansion, >36 causes disease - 27-35: no sx, but if male, risk of expansion in kids - 36-39: reduced pen, may not develop sx - >40: fully penetrant - >60: juvenile onset |
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Hutchinson-Gilford Progeria syndrome |
- short stature, head large for face - prominent scalp veins - generalized alopecia - delayed/crowded teeth - delayed fontanelle closure - pear-shaped thorax - small chin/thin limbs/tight joints LMNA (AD); all de novo, paternal age effect |
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Hypochondroplasia |
- short stature/adult-onset osteoarthritis - rhizo or mesomelia - limited elbow extension - brachydactyly - mild joint laxity/lumbar lordosis - macrocephaly - scoliosis - mild to mod MR; LD FGFR3 (AD) |
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Hypohidrotic Ectodermal Dysplasia (HED) |
at birth: peeling skin, perioral hyperpigmentation, hypotrichosis, hypohidrosis (no sweating), hypodontia - probs w/ hair, teeth, nails, sweat glands EDA/EDAR/EDARADD (XL: 95%, AD/AR: 5%) |
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Incontinentia Pigmenti |
Major: four stages of skin changes - erythema -> blister -> hyperpigmented streaks -> atrophic skin patches minor: hypo/andontia, alopecia, wooly hair, nail ridging/pitting, retinal detachment, MR is rare IKBKG (XLD), most male fetuses miscarry |
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Jervell-Lange-Nielsen syndrome |
- congenital severe to profound bilateral SNHL and prolonged QT interval - at risk for arrhythmia, syncope, & sudden death KCNQ1/KCNE1 (AR); heterozygotes at risk for AD long QT (Romano-Ward syndrome) |
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Joubert syndrome |
- hypotonia in infancy, ataxia later in life - DD/MR - pigmentary retinopathy - M:F = 2:1 - renal disease seen in those w/ retinal involvement NPHP1/AHI1/CEP290/TMEM67 (AR) |
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Kallman syndrome |
- hypogonadotropic hypogonadism - anosmia - delayed pubertal development type 1 also has: mirror hand mvmts, ataxia, GU anomaly, high palate, pes cavus type 2 also has: MR, CL/CP, cryptorchidism, choanal atresia, CHD, SNHL KAL/FGFR1 (XLR/AD) |
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Klinefelter syndrome |
- tall stature - slightly delayed motor/language skills - increased learning problems - testosterone plateaus at age 14 - small fibrosed testicles - azoospermia/infertility - gynecomastia (slight increase in breast ca risk) - high cholesterol - slight increased risk for autoimmune disorders (1%) |
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Krabbe disease |
Infantile: irritability to sensory stimuli, muscle hypertonicity, progressive neurologic deterioration, peripheral neuropathy, white matter disease, elevated CSF production Later onset: 6m-5th decade, weakness, vision loss, intellectual regression - GALC (AR) |
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Lamellar Ichthyosis |
- scaly skin - outward turned eyelids and lips - large, dark plate-like scales covering skin - alopecia - hypohydrosis - thickening of skin on palms of hands & soles of feet (keratoderma) - infants can have dehydration & resp probs TGM1 (AR) |
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Leber Hereditary Optic Neuropathy |
- blurred or clouded vision progressing to degeneration of retinal nerve, followed by optic atrophy MTND1/MTND4/MTND5/MTND6 (mitochondrial) |
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LEOPARD syndrome |
Lentigines Electocardiographic conduction abnormalities Ocular hypertelorism Pulmonary stenosis Abnormalities of the genitalia Retardation of growth Deafness (SNHL) - hypertrophic cardiomyopathy PTPN11 (AD); loss of function - gain of function causes Noonan |
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Li-Fraumeni syndrome |
increased risk of multiple primary tumors: bone, cartilage, soft tissue sarcoma, early-onset breast cancer, spine/brain tumor, Wilm's tumor - proband w/ sarcoma <45y, - FDR w/ cancer <45y, and - FDR/SDR w/ any cancer <45y or sarcoma at any age P53/CHEK2 (AD) |
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Limb-Girdle muscular dystrophy |
AR sarcoglycan: proximal limb weakness, difficulty running/walking, calf hypertrophy, onset age is 3-15y (68% childhood) Caplain AR: same sx, onset 2-40y; 10-30% of all AR cases Dysferlin AR: probs running/walking, foot drop, distal &/or pelvic weakness, transient calf hypertrophy, onset 17-23y - CAPN3/FKRP/LMNA/SGCA/SGCB/SGCS/SGCG/DYSF (most AR, some AD) |
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Long QT (Romano-Ward syndrome) |
- 95% caused by mutations in K+ genes - instability of heart's electrical system - problems with K+ &/or Na+ prolongs repolarization KCNQ1/KCNE1/KCNH2/KCNE2/SCN5A (AD) |
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Marfan syndrome |
Major: CV (dilation/dissection of ascending aorta), skeletal (pectus carnatum/excavatum, reduced upper-to-lower segment or arm span-to-height, scoliosis), eye (ectopia lentis), dura (lumbosacral dural ectasia), fhx pathogenic FBN1 mut, FDR w/ diagnosis minor: CV (dilation of main PA, dilation/disection of descending thoracis/abdominal aorta @ <50y), skeletal (mod pectus excavatum, joint hypermobility, high palate w/ teeth crowding), eye (flat cornea), lung (pneumothorax), skin (striae, hernia) FGN1 (AD); major involvement of 2 body systems and minor involvement of a 3rd |
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McArdle's disease aka Glycogen storage disease type 5 |
- fatigue - muscle pain/cramps during first few minutes of exercise - prolonged/intense exercise can cause muscle damage - can cause red/brown urine and acute renal failure - usually onset is usually teens to twenties PYGM (AR) |
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McCurie-Albright syndrome |
- polyostotic fibrous dysplasia - pathologic fracture - cranial foramina thickening -> deafness/blindness - large, irregular cafe-au-lait spots - precocious puberty - hyperthyroidism - ovarian cysts GNAS (sporadic) |
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Meniere's disease |
- vertigo - tinnitus - full feeling in ear - headache - hearing loss caused by endolymphatic hydrops (increased volume of fluid), can result in mixing of endolymph and perilymph - progressive disorder, difficult to dx; multifactorial |
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Monosomy 1p36 |
most common terminal deletion syndrome - hypotonia - DD - growth retardation - obestiy - microcephaly - orofacial clefting - typical facial features also: minor cardiac malformations, cardiomyopathy, seizures, ventricular dilation, SNHL |
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MEN type 1 (Multiple Endocrine Neoplasia) |
tumor in 2 of: parathyroid, enteropancreatic endocrine tissue, or anterior pituitary, OR - tumor in one AND FDR w/ MEN1 facial angiofibroma collagenoma cafe-au-lait lipoma - MEN1 (AD) |
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MEN type 2 (Multiple Endocrine Neoplasia) |
type A: 2 or more of medullary thyroid carcinoma, pheochromocytoma, or parathyroid adenoma/hyperplasia in a singer person or close relatives type B: mucosal neuromas of lip & tongue, medullated corneal nerve fibers, marfanoid habitus, medullary thyroid carcinoma RET (AD) |
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Multiple Exostoses syndrome |
- exostosis (benign cartliage-capped bony growths) arising from grown plate of long bones or surface of flat bones - limb length inequity & bowed long bones can develop - can have mass effect compression of nerves and blood vessels EXT1/EXT2 (AD) |
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Myotonia Congenita |
- bouts of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally - most often occurs in the legs Becker: usually appears later in childhood than Thomsen's, causes more severe muscle stiffness, particularly in males, may develop permanent muscle weakness over time (not in Thomsen's) - CLCN1; AD (Thomsen), AR (Becker) |
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Myotonic Dystrophy type 1 |
CTG trinuc repeat - mild (50-150): cataracts, mild myotonia - classic (100-1000): muscle weakness/wasting, myotonia, cataracts, arrhythmia, grip myotonia - congenital (>2000): hypotonia, severe generalized weakness @ birth, often w/ resp insuff and early death, MR is common |
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Nemaline Myopathy |
- weakness (usually most severe in face, neck flexors, and proximal limb muscles) - hypotonia - onset can be congenital, childhood, or adulthood ACTA1/NEB/TNNT1/TPM2/TPM3 (AR or AD) - walking prior to 18m is predictive of survival |
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Neurofibromatosis Type 1 |
2 or more: - cafe-au-lait - 2 or more neurofibromas - one plexiform neurofibroma - axillary or inguinal freckling - optic glioma - 2 or more Lisch nodules - sphenoid dysplasia or thinned long bone cortex - FDR w/ NF1 NF1 (AD) - can also have scoliosis |
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Neurofibromatosis Type 2 |
- benign nerve tumors (schwannomas, meningiomas, ependymonas, astrocytoma) - hallmark is bilateral acoustic schwannoma, onset age 18-24y - hearing loss - tinnitus/balance probs - cataracts/mononeuropathy - cafe-au-lait (fewer than NF1) NF2 (AD) |
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Noonan syndrome |
- characteristic facial features - short stature - feeding probs - pulm valve stenosis - HCM - cryptorchidism - renal malformation - scoliosis - increased risk for leukemia/learning disorders PTPN11/SOS1/KRAS (AD); PTPN11 gain of function cause Noonan, loss of function cause LEOPARD |
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Oculocutaneous Albinism |
- nystagmus/strabismus - decreased iris pigment - foveal hypoplasia - decreased visual acquity - white hair/skin - translucent iris three types TYR/OCA2 (AR) |
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Osteogenesis Imperfecta |
- fractures with little or no trauma - relative short stature - blue sclera - dentinogenesis imperfecta - post-pubertal HL - easy bruising several types; type 2 is perinatal lethal, type 3 is severe - COL1A1/COL1A2 (AD, rare AR) |
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Ovarian Teratoma |
46,XX - maternal chroms only - no placental development - mass contains teeth, hair, bone |
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Parkinson disease |
- bradykinesia - rigidity - tremor - asymmetric limb involvement Juvenile onset: AR PARK2 muts, typical features, onset 20-40y - multiple genes, mainly PARK2; AD, AR, multifactorial |
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Partial mole |
triploidy w/ 69 chroms typically d/t dispermy abnl cystic placenta/will have a fetus |
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T13 |
- holoprosencephaly - polydactyly - seizures - microcephaly - midline CL/CP - omphalocele - cardiac/renal anomalies - MR 20% d/t translocation |
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Pendred syndrome |
- bilateral severe SNHL, progressive - temporal bone abnormalities - vestibular abnl; misshapen cochlea and enlarged vestibular canal - goiter in 75% though only 10% have abnl thyroid function SLC26A4 (AR) |
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Polycystic Kidney disease |
AD: enlargement of both kidneys, renal cysts, hematuria, polyuria, flank pain, renal stones, urinary infection, heart valve defects AR: fetal/neonatal death, impaired lung formation, pulm hypoplasia d/t oligohydramnios, renal failure, hepatic fibrosis, most present prenatally or in early infancy PKD1/PKD2/PKHD1 (AD/AR) |
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Prader-Willi syndrome |
Once called H30 syndrome: (Hypotonia, Hypomentia (MR), Hypogonadism, Obesity) - hypothalamic insufficiency - neonatal hypotonia - DD - hyperphagia leading to obesity - short stature - small hands/feet - hypogonadism - MR 3-5Mb del 15q11.2-q13 = ~70% mat UPD = 15% imprinting center defect = 1-2% |
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Pseudoxanthoma Elasticum |
- mineralization of elastic tissue leading to skin, ocular, and vascular damage - in arteries, can lead to thickening wall and blockage - skin may become lax and redundant - angiod streaks in retina can lead to vision loss ABCC6 (AR) |
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PTEN Hamartoma tumor syndrome |
Cowden: presents 2nd/3rd decade, mucocutaneous facial/oral papules, gingival cobblestoning, acral keratosis, GI polyps, macrocephaly, dolicocephaly, incresed risk for breast, thyroid, and endometrial cancers Bannayan-Riley-Ruvalcaba: macrocephaly, polyposis, lipomas, pigmented macules of the glans penis PTEN (AD) |
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Retinitis Pigmentosa |
- can be primary or d/t another disorder - may lead to 'tunnel vision' - muts occur in visual pigments or other proteins involved in normal function of rods and cones > 60 genes cause nonsyndromic; AD, AR, XL |
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Rett syndrome |
- MR - developmental regression - acquired microcephaly - stereotypical wringing hand movements - hyperventilation - paroxysmal laughing - prolonged QD - scoliosis MECP2 (XLD) |
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Rubenstein-Taybe syndrome |
- microcephaly - beaked nose - broad thumbs and toes - cryptorchidism - growth delay - severe MR - congenital heart defect - strabismus/ptosis CREBBP/EP300 (AD) |
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Russel-Silver syndrome |
- low birth wt/slow growth/FTT - hypoglycemia - short stature - small, triangular face w/ distinctive facial features (prominent forehead, narrow chin, small jaw, downturned corners of mouth) - clinodactyly - hemihypertrophy H19/IGF2 (some AD, most sporadic)
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Saethre-Chotzen syndrome |
- coronal synostosis - facial asymmetry - ptosis - 2/3 hand syndactyly - mild-mod DD in minority - short stature - vertebral fusions - CP - maxillary hypoplasia - CHD TWIST1 (AD) |
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SCID (Severe Combined ImmunoDeficiency) |
- missing lymphoid stem cell - few/absent B- and T-cells - hypoplastic thymus d/t T-cell absence - very low IgM, IgA, and IgG reticular agenesis (most severe): common leukocyte stem cell absent; child dies in-utero or shortly after birth |
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Sjogren's disease |
- autoimmune disorder that destroys moisture-producing glands in the body - dry mouth, eyes, vagina, resp tract - can lead to fatigue, memory probs, dry skin - incr risk for lymphatic cancers |
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Smith-Magenis syndrome |
- mild-mod infantile hypotonia - feeding probs and FTT - short stature - brachydactyly - opthal/ORL abnlties - early speech delay w/out hearing impairment - peripheral neuropathy - sleep probs - maladapative behaviors (self-hug, lick & flip magazines) RAI1 (AD), sporadic unless parental translocation |
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Sotos syndrome |
- macrocephaly - pointed chin - tall stature/incr body mass - delayed motor skills - delayed cognitive, verbal, and social dvlpmnt NSD1 (AD) |
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Spinal Muscular Atrophy |
type 1: onset 0-6m, muscle weakness, tongue fasiculations type 2: muscle weakness, onset >6m, finger trembling, low tone type 3: weakness leading to frequent falls or trouble w/ stairs, onset 2-3y, proximal weakness (legs>arms) SMN1/SMN2 (AR); hereditary degeneration of anterior horn cells |
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Spinobulbar Muscular Atrophy |
- lower motor neurons and sensory neurons affected - speech and swallowing (bulbar) muscles also affected - can also include partial androgen insensitivity AR (XLR); CAG repeat expansion in androgen receptor gene |
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Stargardt's disease |
- inherited juvenile macular degeneration (dx <20y) - degeneration of cones/central vision, preservation of peripheral vision ABCA4/ELOVL4 (typically AR) |
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Syndromic Congenital Muscular Dystrophy (Fukiyama MD, Muscle-Eye-Brain, Walker-Waarburg, Congenital MD, type 1) |
- muscle weakness present @ birth - hypotonia and weakness - joint contracture (elbow, hip, knee, ankel, elbow) FCMD/POMGNT1/POMT1/POMT2/LARGE (all AR) |
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Tay-Sachs disease |
infantile: weakness @ 6m, exaggerated startle, sz and vision loss by end of first yr, neurodegneration continues (deaf, cannot swallow, weakening of muscles, eventual paralysis, death in toddler years) juvenile: muscle coord probs, seizure, vision probs starting as young children chronic/adult onset: starts later, progresses more slowly, more rare - HEXA (AR); 6 common AJ muts = 92% |
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What is the only MPS that does not have MR? |
Morquio syndrome (MPS IV) |
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Thalidomide embryopathy |
- drug used to treat morning sickness - causes phocomelia |
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Rubella syndrome |
- cataracts, deafness, and heart defects - 85% of pregs infected in 1st trimester have birth defects and severe probs - after 20 weeks, risk is very small |
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Retinoic Acid embryopathy |
- abnl hindbrain development - retinal/optic nerve abnl - micrognathia
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Fetal Alcohol syndrome |
- short nose w/ a low nasal bridge - hypertelorism - low-set and often malformed ears - short neck - CL/CP - microcephaly - heart defects - hypoplasia of nails and distal phalanges - some cognitive/behavioral probs |
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Maternal Diabetes |
- macrosomia - hypoglycemia - heart/kidney defects - hypocalcemia |
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Branchio-Oto-Renal syndrome |
- SN, conductive, or mixed hearing loss - branchial pits, cysts, and/or fistula - ear pits/tags EYA1 (AD) |
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Alport syndrome |
- hematuria - nephritis w/ progressive renal failure - cataracts, maculopathy - progressive SNHL in late childhood/early adulthood COL4A3/COL4A4/COL4A5 (XL: 80%, AR: 15%, AD: 5%) |
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Stickler syndrome |
- flat facies - CP - myopia - retinal detachment - deafness - epiphyseal abnormalities COL2A1/COL11A2 (AD, some de novo) |
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Treacher Collins syndrome |
- underdeveloped facial bones - CP - conductive HL - malformed ears TCOF1 (AD) |
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Transient Neonatal diabetes mellitus |
- DM in first 6w of life, resolves by 18m - severe IUGR - dehydration - hyperglycemia - occasionally also macroglossia and umbilical hernia HYMA1/PLAGL1, usually UPD isodisomy 6, paternal 6q24 dup, or 6q24 methylation defect |
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Triploidy |
- 3/4 finger syndactyly - ASD/VSD - hydrocephalus - holoprosencephaly - >99% miscarry in first trimester if maternal: small placenta, severe IUGR w/ large asymmetrical head if paternal: hydropic large placenta, well-grown to moderate symmetric IUGR, nl/microcephalic head |
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Tuberous Sclerosis |
- tumors in brain, heart, skin, kidney, eye - seizures TSC1/TSC2 (AD, 2/3 de novo) - contiguous gene deletion syndrome exists that include PKD |
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Turner syndrome |
- congenital lymphedema - growth failure - coarctation of the aorta - hyperlipidemia - gonadal dysgenesis - horseshoe kidney |
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Usher syndrome |
- SNHL - RP - three types depending on severity/onset majority d/t MYO7A/USH2A (AR) |
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VACTERL association |
Vertebral anomalies Anal atresia Cardiac malformations (VSD/PDA/TOF) Tracheoesophageal fistula Esophageal atresia Renal anomalies Limb anomalies (polydactyly, radial aplasia, etc) - diagnosis requires 3 of 7, & is a dx of exclusion |
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Von Hippel-Lindau syndrome |
- hemangioblastoma (cerebellum, retina, spinal cord) - pheochromocytoma (hypertension) - renal cell carcinoma (40%) VHL (AD) |
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Waardenburg syndrome |
- SNHL - heterochromic irides - white forelock - NTD PAX3 (AD) |
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Williams syndrome |
- supravalvular aortic stenosis (75%) - distinctive facial features (elvin) - joint laxity - MR - overly friendly - FTT in infancy - hypothyroidism |
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Wilson disease |
- presents between 3-50y - liver disease (jaundice, autoimmune hepatitis, hepatic failure, chronic liver disease) - movement disorder - disorganized personality - copper storage disorder ATP7B (AR) |
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Wiscott-Aldrich syndrome |
- eczema - thrombocytopenia - prone to infection/autoimmune disorder/leukemia and lymphoma - easy bruising/prolonged bleeding from minor trauma WAS gene (XLR) |
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Wolf-Hirschorn syndrome aka 4p minus aka monosomy 4p |
- 'Greek warrior helmet' - microcephaly - pre/postnatal growth deficiency - MR (variable)/seizures - CL/CP - CHD 4p- deletion, includes WHSC1/WHSC2 87% de novo, 13% d/t unbalanced translocation from a balanced parent |
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X-linked Adrenal Hypoplasia Congenita |
- acute onset adrenal insuficiency - cryptorchidism/delayed puberty carrier females may have adrenal insuff or hypogonadotropic hypogonadism NROB1 gene (XLR) 1/3 are contiguous with DMD deletion 2/3 are isolated CAH (half de novo) |
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X-Linked Adrenoleukodystrophy |
Peroxisomal disorder - late 20s progressive paraparesis - sphincter disturbance - adrenocortical dysfunction ABCD1 gene (XLR) adrenocortical insuff only seen in ~20% of carrier females |
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X-linked Agammaglobulinemia (Bruton's) |
- pneumonia - sinusitis < 5y - sepsis - meningitis - cellulitis BTK gene (XLR) |
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Xeroderma Pigmentosa |
- severe sun sensitivity - progressive neurologic deterioration - acquired microcephaly - progressive SNHL - > 1000 times increased risk for skin and eye neoplasms XPA/XPC/ERCC2/POLH (AR) most common genes |
