Genetics Flashcards
WAGR syndrome
Wilm’s Tumour
Aniridia (no iris)
GU abnormalities
Mental retardation
Teratogenic Exposures
Trisomy 21 Recurrence Risk
- nondisjunction - additional 1% risk on maternal age related risk
- paternal 21:21 translocation - 100%
- paternal 21:14 translocation - 5%
- maternal 21:14 translocation - 15%
Trisomy 13 & 18
Differential Diagnosis of Craniosynostosis
- Crouzon (prominent forehead, beaked nose, prognathism, hypertelorism, cleft lip/palate, midface hypoplasia, proptosis)
- Pfeiffer (hearing loss, pollux/hallux - big toe - varus, +/-syndactyly
- Apert (hearing loss, prominent syndactyly)
Turner vs. Noonan
Inheritance of Fragile X
tri-nucleotide repeat expansion, X-linked?
Diagnostic criteria for NF1
2+ of the following:
- 6 CALM (5mm children, 15mm pubertal)
- 2+ neurofibromas or 1 plexiform neurofibroma
- axillary or inguinal freckling
- optic glioma (< 10)
- 2+ lisch nodules
- tibial pseudoarthrosis or sphenoid dysplasia
- first-degree relative with NF1
Malignancies associated with NF1
- gliomas
- leukemia
- pheochromocytoma
- JMML
- breast cancer
Surveillance of NF1
- annual ophthalmology
- annual physical exam
- MRI only if symptomatic
Natural History of Achondroplasia
Clinical Features of Alagille Syndrome
- AD - JAG1/NOTCH2
- neonatal cholestasis due to paucity of bile ducts
- peripheral pulmonary stenosis
- butterfly vertebrae
- triangular facies
- posterior embryotoxon
Surveillance for Turner Syndrome
Tumour Surveillance for BWS
- Abdominal US every 3 months until 8 years
- AFP levels every 3 months until 4 years
- Annual RBUS from 8 years to adolescence
CHARGE Syndrome
- coloboma
- congenital heart disease (conotruncal or arch abnormalities)
- choanal atresia
- retardation of growth and development
- genitourinary abnormalities (horseshoe kidney, cryptorchidism, microphallus, pubertal delay)
- Ear and extremity abnormalities - semi-circular abnormality, deafness, clubfoot, absent tibia)
Features of Cornelia de Lange Syndrome
- upturned nose
- unibrow
- long eyelashes
- low ears
- GERD
- upper limb differences (small hands, missing fingers/forearms)
- cleft palate
- diaphragmatic hernia
- vision and hearing problems
- excessive body hair
- heart defects
- seizures
- self-injury, ADHD
- developmental delay
Denys-Drash Syndrome
- Wilm’s Tumour (90%) - prophylactic nephrectomy recommended
- Abnormal kidney function - presents as nephrotic syndrome and HTN (diffuse mesangial sclerosis, renal failure)
- DSD (males) - infertile, risk of malignancy
Features of 22q11.2 Deletion Syndrome
- AD inheritance
- developmental delay/psychiatric disorders
- Cardiac - TOF/conotruncal defects, interrupted aortic arch
- abnormal facial features (hooded eyelids, abnormal auricles, bulbous nose with anteverted nares, asymmetric crying faces)
- thymus - immune deficiencies
- cleft palate
- Hypocalcemia due to hypopara
Features of FASD
- cardiac: VSD, ASD, conotruncal heart defects
- Skeletal: joint flexion contractures, pectus, vertebral defects, clinodactyly of the 5th finger
- renal: aplastic, dysplastic, hypoplastic, horseshoe
- ocular: strabismus, ptosis, retinal vascular anomalies
- auditory: CHL or SNHL
- facial features: smooth philtrum, thin upper vermillion, short palpebral fissures, microcephaly - if all 3 present, do not need prenatal alcohol exposure
- developmental delay, impairment in functioning, ADHD (need severe impairment in 3+ domains)
Galactosemia Features
- onset of symptoms by 2nd half of 1st week of life (day 4-7)
- vomiting, feeding intolerance
- cataracts
- liver failure
- jaundice (unconjugated –> conjugated)
- hepatomegaly
- hypoglycemia
- E. coli sepsis**
- expressive language delay
Diagnosis of Galactosemia
- elevated galactose and galactose-1-phosphate in blood
- elevated urine galactitol
- elevated urine reducing substances
- confirmation of diagnosis: direct enzyme assays using erythrocytes
- gene testing with GALT gene
Klinefelter Syndrome
- XXY
- micropenis, cryptorchidism, hypospadias, clinodactyly
- pubertal delay
- infertility
- small, firm testes (< 5ml), small phallus
- tall stature
- adolescent gynecomastia
Leigh Syndrome
Mitochondrial DNA
Neurologic disease with demyelination, gliosis, necrosis, neuronal sparing and capillary proliferation
- lactic acidosis (treat with NaHCO3)
- FTT
- hypotonia
- peripheral neuropathy
- hypertrophic cardiomyopathy
- seizures (avoid VPA)
Investigations:
- mitochondrial genome molecular genetic testing
- blood + cerebrospinal fluid (CSP) lactate levels
- muscle biopsy
- respiratory chain enzyme studies
- MRI shows bilateral symmetric hypodensities in the basal ganglia
Poor prognosis, 50% mortality before 1.5 years of age
Tuberous Sclerosis Criteria
2 major OR 1 major + 2 minor OR pathogenic mutation in TSC1/2
MAJOR
- cortical dysplasia
- subependymal nodules
subependymal giant cell astrocytoma
- facial angiofibromas (>/= 3) or forehead plaque
- ungual fibromas (>/= 2)
- hypomelanotic macules (>/= 3, > 4 mm in diameter)
- Shagreen patch
- Multiple retinal nodular hamartomas
- cardiac rhabdomyoma
- renal angiomyolipoma
- pulmonary lymphangioleiomyomatosis
MINOR
- dental enamel pits (>3)
- Intraoral fibromas (>/= 2)
- retinal achromic patch
- confetti skin lesions
- nonrenal hamartomas
- multiple renal cysts
