Genetics Flashcards
NF1
Autosomal dominant Chr17 (50% sporadic) >6 cafe au lait >2 lisch nodules Axillary freckling Optic glioma >2 neurofibroma/1 plexiform neurofibroma Osseous lesion First degree relative
NF2
Autosomal dominant Chr22 (50% sporadic) Bilateral acoustic neuroma Family history Cataracts Meningiomas
Tuberous sclerosis
Autosomal dominant TS1, TS2 (75% sporadic) >3 Ash leaf lesions Infantile spasms Tubers in brain Giant cell astrocytoma Facial adenoma sebaceum Pitted teeth
Williams
Autosomal dominant 7q11 deletion ELN Hypercalcaemia Small FTT Bright blue eyes - stellate iris Supravalvular aortic stenosis Peripheral pulmonary stenosis Cocktail personality Intellectual disability Developmental delay
ELN point mutation only
Autosomal dominant
Supravalvular AS only
Alagille
Autosomal dominant JAG1, NOTCH2 Short, triangular face Butterfly vertebrae Pulmonary stenosis Conjugated jaundice, paucity of bile ducts Moya Moya
Bracho-Oto-Renal
Autosomal dominal EYA1 Sinus/cyst near sternocleidomastoid Deafness/periauricular tags Renal malformations
Marfan
Autosomal dominant FBN1 Ch15 Very tall, arm span > height Ectopic tennis (upward dislocation of lens) Aortic aneurysms MV prolapse Learning
Ehlers Danlos
Autosomal dominant COL5A Tall, easy bleeding Joint dislocations Berry aortic aneurysms Aortic root dilation
Osteogenesis imperfecta
Autosomal dominant COL1A1, COL1A2 High ALP, hypercalciuria Short stature Blue sclera Hearing loss Opalescent teeth
Type 1 mild
Type2 lethal
Type 3 progressiove
Type 4 moderate
Stickler syndrome
Autosomal dominant COL2A1 Cleft palate Pierre Robin MV prolapse SNHL Hypermobilitiy
Diamond Blackfan Anaemia
Autosomal dominant Triphalyngeal thumb (long thumb that looks like finger) Absent thumb Cataracts Complication - AML
Von Hippel Lindau
Autosomal dominant
VHL Ch3
Multiple tumours - renal*, pancreas, phaeochromocytoma
Haemangioblastomas
Cornelia De Lange
Autosomal dominant NIPBL, SMC1A (most sporadic) Monobrow Hirsutism Short Small upturned nose ASD/VSD
Waardenburg
Autosomal dominant
White forelock
Progressive SNHL
Noonan
Autosomal dominant RASMAPK pathway PTPN11, SOS1 (most sporadic) Webbed neck Widely spaced nipples Wooly hair Sternal deformity Pulmonary stenosis** ASD HOCM Associated malignant hypothermia, Leukaemia Wilm's Single gene testing
Costello
Autosomal dominant RASMAPK pathway HRAS Big babies Loose skin on hands and feet, deep palmar crease FTT HOCM Tumour, sick, rhabdo, neuroblastoma
Cardiofasciocutaneous
Autosomal dominant RASMAPK pathway KRAS Curly sparse hair FTT *** Learning difficulties Developmental delay Seziures HOCM PS
Treacher Collins
Autosomal dominant TCOF1 Midface hypoplasia Cleft palate Ear/eye anomalies
Alpha 1 antitrypsin deficiency
Autosomal dominant SERPINA1 Neonatal hepatitis Jaundice Pale stools Hepatomegaly
Achondroplasia
Autosomal dominant FGFR3 (most sporadic) Inhibits chondrocyte Lethal - thanatophoric dwarfism Telephone handle femur
Apert
Autosomal dominant FGFR2 (most sporadic) Craniosynostosis Exopthalmos Moderate intellectual disability Symmetrical syndactyly Cleft palate
Crouzon
Autosomal dominant FGFR2 Craniosynostosis Hydrocephalus Proptosis Strabismus Normal intelligence Hands, feet
Pfeifer
Autosomal dominant
FGFR2
Skull deformity
Deviated short broad thumb and big toe
ADPCKD
Autosomal dominant PKD1 Chr16* PKD2 Ch4 Bilateral massive kidneys Multiple cysts
Familial adenomatous polyposis
Autosomal dominant
APC
Multiple colonic plyps
Screening colonoscopy from 10 yo
Li Fraumeni
Autosomal dominant p53 Multiple malignancies (sarcoma, breast, leukaemia, adrenal)
MEN1
Autosomal dominant
MEN1
Pancreas, pituitary, parathyroid tumous
MEN2A +2B
Autosomal dominant RET Phaechromocytoma Parathyroid adenoma Medullary thyroid carcinoma
Charcot Marie Tooth
Autosomal dominant CMT1 PMPZZ Foot drop Ataxia Foot deformity Nerve conduction studies Normal CK Dural nerve biopsy *onion bulb* No treatment
CHARGE
Autosomal dominant CHD7 Coloboma/cranial nerve dysfunction Heart - TOF Chonal Atresia Mental Retardation Genital abnormalities TOF/OA, defect in thyme development
Hypomelanosis of Ito
Autosomal dominant
Hypopigmented whorls
Seizures
Mental retardation
Osler-Weber-Rendu/Hereditary Haemorrhagic Telangiectasia
Autosomal dominant Skin lesions AVM GI bleeding Haematuria Recurrent epistaxis
Gilbert disease
Autosomal dominant
Mutation glucoronyltransferase
Intermittent painless unconjugated jaundice
Peutz-Jeghers
Autosomal dominant
Dark spots on lips
Risk polyps in GIT with possible malignant transformation
Myotonic dystrophy
Autosomal dominant
DMPK GTG triplet repeat
Anticipation (mum)
Clench hands difficult to open - check handshake in parents
Myotonia, muscle wasting, cataracts, cognitive delay
Huntingtons
Autosomal dominant
CAG triplet repeat >40
Anticipation (Dad)
Depression, choreiform movements, caudate atrophy
RASMAPK Pathway
Noonans
Costello
Cardiofasciocutaneous
NF1
Cystic fibrosis
Autosomal recessive
CFTR Chr7
1. G542X most severe - can’t make CFTR
2. DF508** most common - can’t fold CFTR Rx lumicaftar
3. G551D most treatable - normal CFTR protein but can’t transport Rx Ivacaftar
4. R117H most asymptomatic - normal CFTR some transport some can’t - incidental finding in fertility testing
Wilson’s disease
Autosomal recessive ATP7B Think in any child with abnormal movements/psychiatric disease + abdominal pain Liver <10yo Neurological >10yo Kayser-Flesher rings Dx: low ceruloplasmin, high urinary copper, liver biopsy to confirm Rx: copper chelation
Pendred
Autosomal recessive
Congenital SNHL, goitre
Fanconi anaemia
Autosomal recessive FANCA, FANCB Think if cytopaenia + congenital malformation especially thumbs Aplasia of radius Short Ash leaf/cafe au lait PDA, ASD/VSD, situs invertis AML Dx: anaemia, high HbH, high AFP Chromosomal breakage/fragility studies
Homocysteinuria
Autosomal recessive CB5 Tall and dumb Ectopia lentis (downward dislocation of lens) Malar flushing Livedor reticular Seizures Dx: homocysteine blood/urine, plasma amino acids
ARPKD
Autosomal recessive
PKHD1 both kidneys enlarged cysts throughout
Neonate can get POTTERS
Hypertension
Bilateral flank mass
Renal/liver dysfunction
DDH/talipes/pulmonary hypoplasia due to severe oligohydramnios
Gitelman
Autosomal recessive
Defect Na/K transport
Nocturia, parenthesis, joint pain
Same as thiazide diuretic (low K, low H, high glucose, high uric acid. Low urine calcium)
Bartter
Autosomal recessive SLC2A1 Polyuria, polydipsia, nephrocalcinosis Low Na, K, Cl High urinary Ca (same as loop diuretic) IVF/replace salts
Alpha thalassaemia
Autosomal recessive
Chr 16
HBA1, HBA1
Beta thalassaemia
Autosomal recessive
Chr 11
Sickle cell anaemia
Autosomal recessive
HBB
Risk gallstones
Glanzmann
Autosomal recessive
Normal platelet number, can’t aggregate
Smith-Lemli-Opitz
Autosomal recessive DHCR7 Cholesterol synthesis problem Poor growth** Cleft palate Hypotonia Congenital cataracts Absent corpus callosum ID