Genetics and syndromes Flashcards
What causes Down syndrome?
1 in 600-700 live births
Incidence increases with maternal age
• 95% of babies with Down syndrome have trisomy 21- usually due to non-disjunction during maternal oogenesis
o 2% are the result of a Robertsonian translocation- extra chromosome 21 is added onto another chromosome
o 2% are mosaic, with a normal cell line as well as the trisomy 21 cell line
How is screening done for downs syndrome?
Measure biochemical markers in blood samples and often used nuchal thickening on US to identify increased risk of Down syndrome in foetus when this increased risk is identified, then amniocentisis is offered to check foetal karyoptype
• After having one child with trisomy 21 due to non-disjunction- the risk of recurrence is given as 1 in 200 for mothers under 35 yrs, but remains similar to their age-related population risk for those over the age of 35 yrs
What is the risk of Down syndrome according to maternal age?
All ages: 1 in 650
20: 1 in 1530
30: 1 in 900
35: 1 in 385
37: 1 in 240
40: 1 in 110
44: 1 in 37
What are the clinical features present in Down syndrome?
• Generalised hypotonia and marked head lag
o Small low-set ears
o Up-slanting eyes
o Prominent epicanthic folds
o A flat facial profile
o Protruding tongue
o Brushfield’s spots apparent in the iris- whitish spots
• Flat occiput (brachycephaly) and short neck
• Mildly short stature
• Intellectual impairment become apparent- IQ scores range from 25 to 70
• Social skills often exceed other intellectual skills
What are the typical limb features in Down syndrome?
o Short broad hands- brachydactyly
o Short incurved little fingers- clinodactyly
o Single transverse palmar crease
o Wide ‘sandle’ gap between the 1st & 2nd toes
What are associated conditions of Down syndrome?
• 40-50% have congenital heart disease- mostly AVSD, but also ASD, VSD & Tetraology of Fallot • GI problems o Duodenal atresia o Anal atresia o HSD • Increased risk of infection • Developmental hip dysplasia • Eczema • Deafness- both sensorineural and conductive • Cataracts • Leukaemia (1%) • Acquired hypothyroidism
How is Down syndrome diagnosed?
• Diagnosis is confirmed by a chromosome analysis showing an additional chromosome 21- most cytogenetic laboratories are able to offer a rapid analysis in order to establish the diagnosis quickly (1-2 days) eg. interphase FISH – fluorescence in situ hybridization
What are the long term conditions associated with Down syndrome?
- Delayed motor milestones
- Moderate to severe learning difficulties
- Small stature
- Increased susceptibility to infections
- 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 management for Down syndrome?
Genetic counselling- parental chromosome analysis
Support organisations- Down association
Long term follow up- paediatrician and a physio
Routinely test TFT
Refer for audiology and ophthalmic assessment 1-2 yearly
Educational support
What is the prognosis for Down syndrome?
• If death from congenital cardiac disease is excluded- life expectancy is well into adult life, but most develop
Alzheimer’s by 40yrs
• Majority of adults can live semi-independently with supervision
What is turner syndrome?
1 in 2500 females
Most girls have a single X chromosome (45, X)- usually due to non-disjunction
• In 50% of girls with Turner’s: there are 45 chromosomes with only one X chromosome- the other cases have a deletion of the short arm of one X chromosome, an isochromosome that has two long arms, but no short arm
• The presence of a Y chromosome may increase the risk of gonadoblastoma
• The incidence does not increase with maternal age- risk of recurrence is very low
What are the clinical features if Turner syndrome?
- Short stature- typical growth rate beings to falter from 3-5yrs due to underlying skeletal dysplasia- mean final height is consistently 20cm below the norm
- Broad neck
- Ptosis
- Wide carrying angle of elbows- cubitas vulgas
- Widely spaced hypoplastic nipples
- Low posterior hairline
- Excessive pigmented naevi
- Spoon-shaped nails
- Recurrent otitis media
- Puffiness of hands & feet as a neonate
- Normal intellectual function in most
What are the diagnostic investigations for Turner syndrome?
95% of Turner’s result in early miscarriage (US- oedema of neck, hands/feet or cystic hygroma)
Chromosome analysis offered to all girls with short stature
Karyotype confirms diagnosis
What are the associated abnormalities of Turner syndrome?
o Congenital heart disease-15-50%, especially coarctation of the aorta and VSD
o Structural renal anomalies (30%) eg. horseshoe kidney or unilateral renal agenesis
o Hypoplastic ‘streak’ ovaries- 1o amenorrhoea & infertility, ovarian dygenesis and consequent gonadal failure results in loss of pubertal growth spurt
What is the management of Turner syndrome?
Daily SC injections of high dose recombinant human growth hormone- increases final height, although individual response is variable Oral oestrogen (ethinylestradiol) is required to induce puberty between 12-14yrs Combination therapy (anabolic steroids & oxandrolone)- may further improve final height
