Genetics Flashcards
low set ears, microcephaly depressed nasal bridge CL+P polydactyly holoproencephaly cardiac defects
T13 (Patau)
cardiac - ASD, VSD
Fragile X clinical features
- Prominent forehead, long narrow face
- High arch palette, cleft palette
- Dental crowding/malocclusion
- Strabismus, nystagmus, ptosis
- Macro-orchidism
- Connective tissue dysplasia
- Feeding problems
- Hypotonia
- Seizures
- Chronic OM
Classic presentation:
Male, Intellectual Disability, autistic behaviour, macroorchidism, hyper extensible fingers and characteristic facial features
Fragile X Genetic Problem
- X linked but females can have too
- FMR1 (fragile X mental retardation 1)
- Unstable CGG trinucleotide repeat
- worse clinical severity with longer CGG repeats
Fragile X Cognitive Problems
- moderate to severe mental retardation
- language delay
- Females with fragile X show varying degrees of intellectual disability and/or learning disabilities
Turner Syndrome Phenotype
- short stature/growth deficiency
- lymphedema hands and feet
- webbed neck
- low posterior hair line
- broad chest with inverted or hypoplastic nipples
- cubitus valgus
- delayed puberty/menarche
- hearing loss/recurrent OM
- renal abnormalities
- CVS abnormalities
Turner Syndrome Genetic Problem
- haploinsufficiency of specific genes on X chromsome
- 80% girls with Turner’s inherit single X chromosome from the mother, 20% from father
Turner Syndrome Cardiac Abnormalities
- Bicuspid Aortic Valve = most common malformation
- can lead to aortic to aortic root dilitation - Coart of the aorta = 2nd most common
Less common - MV prolapse, partial anomalous pulm venous drainage, HLHS
Tuberous Sclerosis
DDx Major Criteria
- hypomelanoic macules (>/=3, 5mm diameter)
- angiofibromas (>/=3) (skin)
- ungal fibromas (>/=2) (skin)
- shagreen patch (skin)
- multiple retinal harmatomas (CNS)
- cortical dysplasias (CNS)
- subependymal nodules (CNS)
- subependymal giant cell astrocytomas (CNS)
- cardiac rhabdomyoma - cardiac
- lyphangioleiomyomatosis (LAM) - lung
- angiomyolipomas (>/=2) - renal
Turner Syndrome AAP Health Supervision Medical Txts
- Short stature - GH therapy (as young as 2 yrs)
- CVS abnormalities - pts with bicuspid aortic valve, aortic stenosis, coarct of the aorta or systemic HTN need close follow up for aortic dilation
- HTN - up to 40% have HTN, treat and look for renal/cardiac cause
- Hearing loss
- Strabismus/Cardiofacial abnormalities
- Obesity/Glucose intolerance
- UTI - 1/3 have structural malformations (double collecting system, abnormal vascular supply)
- Thyroid Dysfunction/Autoimmune Disorders ( Hashimoto, Celiac, IBD, JIA)
- Ortho - Congenital DDH
- Psychosocial support
Prader-Wili Sydnrome Genetics?
- 70% have lack of expression of genes on paternally inherited chromosome 15 spanning the PWS region
- 20% have maternal uniparental disomy (UPD) = child inherits both copies of chromosome 15 from the mother and none from the father
-less common - imprinting error, balanced translocation
How does Prader Willi present in infants and then in childhood?
- infants - significant hypotonia, early feeding problems and difficulty gaining weight
- childhood - hyperphagia leading to obesity, food seeking behaviors
without adequate weight control can get: diabetes, OSA, R sided heart failure
Prader Willi Special considerations AAP guildelines
- Nutrition
- Feeding tubes (NG or Gtube)
- Endocrine considerations and Recombinant Human Growth Hormones ( should look for OSA with polysonmongraphy)
- Behavioural Food Controls
- Hypogonadism
- Behavioural management - ODD, compulsive, ood seeking, OCD
Willams Syndrome Genetics
- Mircodeletion of chromosome 7
- 99% homozygous deltion of 7q11.23
- can use FISH to confirm dx
William Syndrome Phenotype
characterized by:
- dysmorphic faces
- CVS disease (supravalvar aortic stenosis, peripheral pulmonary artery stenosis, coarct)
- risk for hypertension
- mental retardation
- characteristic cognitive profile
- HYPERcalcemia
Facial features
- periorbital fullness
- short nose with bulbous nasal tip
- long philitrum
- wide mouth, full lips
- starburst pattern to irides (stellate iris)
William Syndrome Behaviour Characteristics
- overfriendliness and empathetic nature
- ADHD, Anxiety
- cognitive and lang delay universal
- weakness with visuospatial cognition
