Genetics Flashcards
What are the clinical features of Down Syndrome?
- Developmental delay and ID
- Characteristic facial features
- Muscle hypotonia in infancy
- Congenital heart disease
- GORD
- coeliac disease
- Hypothyroidism
- Leukaemia
- Early onset dementia
What are consequences of Turner Syndrome?
-Physical: short, shield shaped chest with wide nipples
- lymphoedema
- Cardiac anomalies (coarctation of aorta)
- primary ovarian failure
- neurocognitive difficulties
- endocrinopathies such as hypothyroid
What are features of Kleinfelter?
Low muscle tone
Developmental delay
Hypoandrogenism
Metabolic syndrome
Hypothyroidism
VTE
Osteoporosis
Increased risk of cancer
What are features of Di George syndrome?
- Congenital heart disease esp conotruncal malformations
- palate abnormalities
- Characteristic face (low set ears, wide eyes)
- Learning difficulties
- immune deficiency
What are features of Huntington disease?
- movement disorder: chorea, bradykinesia, rigidity, dystonia
- impaired voluntary motor function
- cognitive decline
- psychiatric disturbance
What are Spinocerebellar ataxia and their mode of inheritance?
Hereditary ataxias characterised by degeneration of cerebellum +/- spinal cord
AD inheritance: over 40 types which can be repeat expansion with anticipation or non-repeat expansion
What are the clinical features of spinocerebellar ataxia?
-onset age 30-40 years (some in childhood)
- start with unsteady gait
- difficulty with co-ordination
- Dysarthria and dysphagia
- oculomotor abnormalities
- Non-Ataxic: movement disorder, epilepsy, motor/somatic, urinary symptoms, sleep disorders
What are features of myotonic dystrophy?
Mild - cataract, mild myotonia, diabetes
Classic - muscle weakness + wasting, myotonia, cataract, cardiac conduction abnormality, endocrinopathy, shortened life span
Congenital - hypotonia, generalised weakness at birth, respiratory insufficiency, ID, premature death
What are features of Duchenne Muscular Dystrophy?
Presents in childhood with delayed motor milestones
Proximal weakness
Elevated CK (10xULN)
Rapidly progressive
Associated with dilated cardiomyopathy
What are features of Becker Muscular dystrophy?
Later onset muscle weakness, proximal > distal
Calf muscle hypertrophy
Elevated CK (5x ULN)
Preserved neck flexor strength
Associated with dilated cardiomyopathy
What are feature of DMD-associated dilated cardiomyopathy?
LV dilatation and CHF
Presents in males 20-40s, rapid progressing
Later onset and slower progression in women
CK increased
What are the clinical features of Marfan syndrome?
Eyes: myopia and ectopia lentis, increased risk of retinal detachment, glaucoma and cataracts
Skeletal: bone overgrowth, joint laxity and reduced joint mobility, long extremities, chest deformity, scoliosis, flat feet, protrusio acetabuli
Cardiovascular: Aortic dilatation, MV prolapse +/-MR, TV prolapse, proximal PA enlargement
Other: striae, bulla
What are the diagnostic criteria of Marfan syndrome in someone WITHOUT a family history?
- Aortic Z-score > 2 and ectopia lentis
- Aortic Z-score > 2 and FBN-1 mutation associated with aortic aneurysm
- Aortic Z-score > 2 and systemci score > 7
- Ectopia lentis AND FBN-1 mutation associated with aortic aneurysm
What is the diagnostic criteria of Marfan syndrome for someone WITH a family history?
- Ectopia lentis and 1st degree relative with Marfan
- Systemtic score >7 and 1st degree relative with Marfan
- Aortic Z-score > 2 and 1st degree relative with Marfan
What are the clinical features of Noonan syndrome?
-Short stature
-Characteristics: broad neck, wide spaced nipples, ptosis, low set ears, short wide nose
-CV: PV stenosis, HCM
- developmental delay
- coagulation defects
- lymphatic dysplasia
- Cryptorchidism
-Neoplasms: neuroblastoma, ALL, AML, JMML, low grade glioma, rhabdomyosarcoma
What are clinical features of RASopathies?
-craniofacial malformation
-congenital heart disease
- short stature, failure to thrive
- neurocognitive impairment
- cancer predisposition
How is NF1 diagnosed?
Clinical diagnosis:
2 or more of:
- 6 or more cafe au lait spot (>15 mm)
- 2 or more neurofibroma OR 1 plexiform neurofibroma
- Axillary or groin freckling
- Lisch nodules (brown nodules in eyes)
- optic pathway glioma
- 1st degree relative with NF1
- Sphenoid wing dysplasia OR thinking of lone bone cortex
Genetic diagnosis if uncertain or for reproductive considerations
What are clinical features of TSC?
Tumours of heart, skin, brain, lungs and kidneys
Seizures
TSC-associated neuropsychiatric disorder
When should a genetic basis of hypertrophic cardiomyopathy be suspected?
Asymmetric thickening of myocardium >15 mm not attributable to hypertension or valve disease
What is the treatment of hypertrophic cardiomyopathy?
- Treatment of heart failure via medications
- Treatment of obstruction via surgery, alcohol ablation
- Treatment of arrhythmia via medications
- ICD for primary or secondary prevention (guided by sudden cardia death risk assessment)
