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
William Syndrome Medical Evaluation
- cardio evaluation
- genitourinary evaluation (U/S, UA, Cr/BUN)
- Calcium determinations (Serum Ca, Spot Ca/Cr)
- Thyroid function
- Optho evalution - to look for strabismus, ambloypia
Marfan Cardinal Features
1) Ocular
- ectopic lentis (hallmark feature)
- myopia most common ocular feature
- increased risk for retinal detachment, glaucoma and early cataracts
2) MSK
- bone overgrowth
- pectus excavatum/carinatum
- scoliosis/kyphoscoliosis
- protrusio acetabuli (acetabulum of the hip abnormally deep)
- joint laxity
- long narrow faces with deep set eyes
3) CVS
- MVP prolapse with CHF leading cause of CVS morbidity and mortality
- significant risk of aortic dissection or rupture when maximal aortic dimension reaches approx 5 cm in adults
- echo at dx, 6 mon then early (if aortic dilations <0.5 cm/yr
- restrict contact, competitive sports and isometric exercise
other considerations:
resp: spontaneous pneumo, decrease pulm reserve, sleep apnea
integument: stretch marks, hernias
dural ectasia: can lead to boney erosion and nerve entraptment
dental: dental crowding
Marfan genetics
AD inheritance
mainly caused by defects in FBN1, the gene that codes for the protein fibrillin
multisystem disorder of Connective tissue
Marfan clinical features
excess linear growth ectopica lentis, retinal detachment, gluacoma scoliosis (50%) dilated aorta, AV insuff, spontaneous pneumotx dural ectasia IQ normal
Marfan screening @ dx
ECHO Ophtho referral MSK exam (scoliosis, joint laxity, pectus) review ddx, genetic examine Family support group
Marfan screening
surveillence
ECHO - q1y from 1 yo
Ophtho - q1y from 1 yo
Bone agex1 @ 6 - 12yo
Acondroplasia 3 phenotypic features
- normal trunk length
- bowing of the legs
- rhizomelic (shortening of the proximal long bones)
Achondroplasia Medical management
- monitor for spinal stenosis
- osa
- hearing- at risk for AOM
- restrictive lung disease
- pregnancy counselling - c/s
- bowing of the legs surgery
NF 1 Diagnostic Criteria
2/7
• 6+ cafe au lait spots >/= 5mm in longest diameter pre-puberty or >/= 15mm in post-puberty
o 5+ lesions by 1 year of age in 80% of cases, but some have none
• 2+ neurofibromas of any type or 1 plexiform neurofibroma
o Plexiform neurofibromas in 25% of patients
• Freckling in axilla in inguinal regions
• Optic (pathway) glioma
o Irreversible visual loss if damage to the pathway occurs
• 2+ iris hamartomas (aka Lisch nodules)
• Distinctive osseous lesion – such as sphenoid wing dysplasia or cortical thinning of long bone cortexes, with or without pseudoarthrosis (2-3%)
• First degree relative with NF1 by above criteria (50% of cases are familial)
NF 1 Complications
- cognitive defects/learning disability, ASD
- 2x as likely for seizures
- peripheral neuropathy
- HTN and renal vascular disease
- Cancers - malignant peripheral nerve sheath tumor, pheo, rhabdomyosarcoma, and optic glioma
- optho and HTN check yearly till age 8 and then every 2 years
- sunscreen - higher risk of skin cancer
Tublersclerosis Management
- baseline EEG
- MRI brain every 1 - 3 years
- baseline echo
- optho referral
- renal ultrasound
