Genetic disorders Flashcards
Genetic testing
is now available for many common hereditary disorders, such as:
HFE genes for haemochromatosis.
Presymptomatic DNA tests for the hereditary neurological disorders, such as Huntington disease
Predective DNA testing for some forms of hereditary cancer, such as breast and colon cancer, and in the future for cardiovascular disease and diabetes.
Carrier screening
The presence of common mutations in severe recessive (autosomal and X-linked) disorders means that carrier screening in a community can be performed.
The disorders for which this commonly occurs are:
- thalassaemia
- Tay–sachs disease
- cystic fibrosis
The reproductive triple carrier screening test is for:
- cystic fibrosis
- fragile X syndrome
- spinal muscular atrophy
The non-invasive prenatal test on pregnant mothers is an aneuploidy test for:
- 21 Downs syndrome
- 18 Edward syndrome
- 13 Patau syndrome
Newborn screening can test for 25 or more conditions including:
- phenylketonuria
- galactosaemia
- hypothyroidism
Specific important genetic disorders
Haemochromatosis: an autosomal recessive (AR) disorder
Thalassaemia: AR
Cystic fibrosis: AR
Congenital adrenal hyperplasia (AR)
Neurofibromatosis: AD two types:
- NF2—peripheral type (von Recklinghausen’s disorder) light-brown skin patches + skin tumours + axillary freckles
- NF2—central type, bilateral acoustic neuromas
- No specific treatment: refer to a neurofibroma clinic
Duchenne muscular dystrophy:
- X-linked recessive condition
- male child + gait disorder + bulky calves
- most are wheelchair bound by 10–12 yrs
- most die of respiratory problems by age 20
Glucose-6-phosphate dehydrogenase deficiency (favism)
- neonatal jaundice (check those at risk)
- most symptomless
- episodic acute haemolytic anaemia triggered by antioxidants, infections, some drugs & fava bean
Galactosaemia
- autosomal recessive disorder (1/60 000 births)
- inability to metabolise galactose to glucose
- infants become anorexic and jaundiced with milk
- management is lactose-free formula e.g. soy
Familial hyperlipoproteinaemia
- familial hypercholesterolaemia
- familial combined hyperlipidaemia
- homozygous patients → atherosclerotic disease in childhood
- heterozygous patients manifest in 30s or 40s
Spinal muscular atrophy
- autosomal recessive disorder (1 in 6000 births)
- carriers 1 in 40
- at least 4 types with SMAI rarely living >2 years
- affects motor neurones causing atrophy of muscles
- no cure at present and treatment is supportive
- claimed to be the leading cause of infant death
Inherited adult onset neurological disorders
Huntington disease: autosomal dominant (AD)
- chorea + abnormal behaviour + dementia
- onset usually 35–55 yrs
- usually fatal outcome 15–20 yrs
- offspring have 1 in 2 risk
- no current cure or specific treatment
Creutzfeldt–Jacob disease & other prion diseases
Familial Alzheimer disease
Familial epilepsy
Familial motor neurone disease
Muscular dystrophies & myotonic dystrophy
Friedreich’s ataxia
Mitochondrial disorders: includes MELAS syndrome (encephalopathy, lactic acidosis, stroke)
Others
Hereditary haemoglobinopathies and haemolytic disorders
Thalassaemias
Sickle cell disorders esp. in Africans
Hereditary spherocytosis
G-6-PD deficiency
Bleeding disorders
Haemophilia A & B
Von Willebrand disease
Inherited thrombocytopenia
Hereditary haemorrhagic telangiectasia
Thrombophilia
Factor V Leiden gene mutation
Prothrombin gene mutation
Protein C deficiency
Protein S deficiency
Antithrombin deficiency
Chromosomal/microdeletion syndromes (childhood expression)
Down syndrome
Fragile X syndrome
Prader–Willi syndrome
Williams syndrome
Angelman syndrome
- puppet-like ataxia (‘happy puppet’)
- hand flapping; seizures
- microcephaly by 2 yrs
- speech and intellectual impairment
Noonan syndrome (AD):
- characteristic facies + short stature + pulmonary stenosis
- affects both sexes
Tuberous sclerosis (epiloia) (AD):
- facial rash + intellectual disability + seizures
Marfan syndrome (AD):
- tall stature + dislocated lens and myopia + aortic root dilatation (prone to dissection)
- high arched palate
- long digits—arachnodactyly
- mitral valve prolapse
Sex chromosome abnormalities
Klinefelter’s syndrome
- XXY genotype
- lanky men + small testes + infertility ± intellectual disability
- treatment: transdermal testosterone
Turner’s syndrome
- XO karyotype
- short stature + webbed neck + typical facies
Fetal alcohol syndrome
Caused by teratogenic effects of alcohol
incidence 2 in 1000 live births
Typical facies + (severe cases) growth retardation + microcephaly
Skeletal abnormalities
