Genetics Flashcards
What are the down syndrome features present at birth?
Typical facial appearance Hypotonic Flat occiput Single palmar creases Incurved fifth finger Wide 'sandal' gap between the big and second toe
What is the typical craniofacial appearance in down syndrome?
Round face and flat nasal bridge
Upslanted palpebral fissures
Epicanthic folds (a fold of skin running across the inner edge of the palpebral fissure)
Brushfield spots in iris (pigmented spots)
Small mouth and protruding tongue
Small ears
Flat occiput and third fontanelle
What are the anomalies associated with down syndrome that don’t involve the typical craniofacial appearance?
Short neck Single palmar creases Incurved fifth finger Wide 'sandal' gap between toes Hypotonia Congenital heart defects (AV canal defect) Duodenal atresia Hirschsprung disease
What are the long-term medical problems associated with downs syndrome?
Delayed motor milestones
Moderate to severe learning difficulties
Small stature
Increased susceptibility to infection
Hearing impairment from secretory otitis media
Visual impairment from cataracts, squints, myopia
Increased risk of leukaemia and solid tumours
Risk of atlanto-axial instability
Increased risk of hypothyroidism and coeliac disease
Epilepsy
Alzheimer’s disease
What is the main cytogenetic cause of down syndrome?
Meiotic non-disjunction
What are some other chromosomal abnormalities apart from down syndrome?
Edwards syndrome
Patau syndrome
Turner syndrome
What are the clinical features of Edwards syndrome?
Low birthweight Prominent occiput Small mouth and chin Short sternum Flexed, overlapping fingers 'Rocker-bottom' feet Cardiac and renal malformations
What are the clinical features of Patau syndrome?
Structural defect of brain Scalp defects Small eyes (microphthalmia and other eye defects) Cleft lip and palate Polydactyly Cardiac and renal malformations
What are the clinical features of Turner syndrome?
Lymphoedema of hands and feet in neonate, which may persist Spoon-shaped nails Short stature - a cardinal feature Neck webbing or thick neck Wide carrying angle (cubitus valgus) Widely spaced nipples Congenital heart defects (coarctation of the aorta) Infertility Hypothyroidism Renal anomalies Pigmented moles Recurrent otitis media Delayed puberty Normal intellect function in most
How do you treat Turners syndrome?
Growth hormone therapy
Oestrogen replacement for development of secondary sexual characteristics at the time of puberty
What are the clinical features of Klinefelter syndrome?
Infertility Hypogonadism with small testes Pubertal development may appear normal Gynaecomastia in adolescence Tall stature Intelligence usually in the normal range, but some have educational and psychological problems
What is Mendelian inheritance?
The transmission of inherited traits or diseases caused by variation in a single gene in a characteristic pattern.
What are some examples of autosomal dominant disorders?
Ehlers-Danlos syndrome Familial hypercholesterolaemia Huntington disease Marfan syndrome Myotonic dystrophy Neurofibromatosis Osteogenesis imperfects
What is the most common mode of Mendelian inheritance?
Autosomal dominant
Chromosomally, how would you summarise autosomal dominant inheritance?
Affected individual carries the abnormal gene on one of a pair of autosomes
What are the chances of inheriting the abnormal gene from an affected parent in autosomal dominant inheritance?
1 in 2 chance, 50%. But there may be variation in expression (severity), non-penetrance, no family history (new mutation, parental mosaicism, non-paternity)
What is non-penetrance?
It refers to the lack of clinical signs and symptoms in an individual who has inherited the abnormal gene.
What is parental mosaicism?
A healthy parent harbours the mutation only in some of their cells e.g. in their gonads
What are some examples of autosomal recessive disorders?
Congenital adrenal hyperplasia Cystic fibrosis Freidreich ataxia Sickle cell disease Thalassaemia
Chromosomally, how would you summarise autosomal recessive inheritance?
Affected individuals are homozygous for the abnormal gene, each unaffected parent will be a heterozygous carrier
What is the risk of two carrier parents having an affected child in an autosomal recessive disease?
1 in 4 risk. Risk of these disorders is increased by consanguity and within specific populations
What sort of pathways do autosomal recessive disorders usually affect?
Autosomal recessive disorders often affect metabolic pathways, whereas autosomal dominant disorders often affect structural proteins
How does X-linked recessive inheritance affect males and females?
Males are affected.
Females can be carriers but are usually healthy or have mild disease
How would offspring be affected in an X-linked recessive disorder?
Each son of a female carrier had a 50% risk of being affected.
Each daughter of a female carrier has a 50% risk of being a carrier.
Daughters of affected males will all be carriers
Sons of affected males will not be affected.
