Genetics Flashcards
What is achondroplasia
Autosomal dominant condition, with abnormal conversion of cartilage to bone (ossification), particularly in long bones
Majority due to de novo mutation
Clinical features of achondroplasia
disproportionate short stature from shortening of limbs
Rhizomelia - short proximal limb
Acromilia - short distal limb (hands, feet)
Mesomelia - short forearm, tibia/fibula
large head
frontal bossing
depression of nasal bridge
lumbar lordosis
short and broad hands
Types of genetic disorders
Chromosomal abnormalities
Action of single gene
Unusual genetic mechanisms
Epigenetics - environmental factors influence gene expression
What is Down’s syndrome
Trisomy 21
Most common autosome trisomy
What are the different types of inheritance of Down’s syndrome and their prevalence
Meiotic Non disjunction - 94%
Robertsonian Translocation - 5%
Mosaicism - 1%
What happens in meiotic non disjunction
Do maternal chromosomes need to be tested
At meiosis, chromosome 21 pair fails to separate thus one gamete has two chromosome 21s
Fertilisation of gamete with 2 chromosome 21s leads to zygote with trisomy 21
No
What is robertsonian translocation
Is parental chromosomal analysis required?
Chromosome 21 joins onto chromosome 14
Can give rise to phenotypically normal gamete with 45 chromosomes - translocation carrier
Can give rise to Translocation Down’s syndrome - 46 chromosomes but trisomy 21
Yes - parent may be translocation carrier, risk of recurrence high if parent is carrier and <1% if neither are carriers
What is mosaicism
Some cells normal and some cells have trisomy 21
Due to formation of normal zygote from non-disjunction at mitosis
Craniofacial features of Down’s syndrome
Round face and flat nasal bridge Upslanted palpebral fissures Epicanthic folds Brushfield spots on iris Small mouth and protruding tongue Small ears Flat occiput
Non-facial features of Down’s syndrome
Short neck Single palmar creases Incurved and short fifth finger Wide ‘sandal’ gap between first and second toes Hypotonia Congenital heart defects (40%) Duodenal atresia Hirschsprung’s disease
Long term complications of Down’s syndrome
Great individual variability in survival, degree of learning difficulty, development of complications
Delayed motor milestones
Learning difficulties
Short stature
Increased susceptibility to infections
Hearing impairment - secretory otitis media
Visual impairment - cataracts, squints, myopia
Obstructive sleep apnoea
Increased risk of hypothyroidism and coeliac disease
Epilepsy
Acquired hip dislocation and atlantoaxial instability
Increased risk of leukaemia and solid tumours
Early onset Alzheimer’s disease
What is Edwards Syndrome
Trisomy 18
What is Patau Syndrome
Trisomy 13
Clinical features of Edwards Syndrome
Low birthweight Flexed, overlapping fingers Rocker-bottom feet Short sternum Small mouth and chin Prominent occiput Cardiac and renal malformations
Clinical features of Patau syndrome
Structural brain defect Scalp defect Small eyes, eye defects Cleft lip and palate Polydactyly Cardiac and renal malformations
