Syndromes Flashcards
What is the incidence of Down syndrome?
Incidence is 1 in 600-700 live births- this incidence increases with increasing maternal age
95% of babies with Down syndrome have trisomy 21- usually due to non-disjunction during maternal oogenesis
What are other chromosomal abnormalities which lead to Down syndrome?
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
What is meiotic non-disjunction?
most cases result from an error at meiosis when the pair of chromosome 21s fail to separate, so that one gamete has two chromosome 21s and one has none
What is the risk in translocation Down syndrome?
the risk of recurrent is 10-15% if the mother is translocation carrier and 2.5% if the father is carrier
What is mosaicisim?
some cells are normal and some have trisomy 21- usually arises from formation of the chromosomally normal zygote by non-disjunction at mitosis, but can arise by later mitotic non-disjunction in a trisomy 21 conception
What screening tests are pregnant women offered for Down syndrome?
screening tests measuring 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
What is the risk of recurrence for Down syndrome?
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 in different maternal ages?
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 of Down Syndrome?
• Usually presents at birth
• Generalised hypotonia and marked head lag
• Facial features
o Small low-set ears
o Up-slanting eyes
o Prominent epicanthic folds
o A flat facial profile
• Flat occiput (brachycephaly) and short neck
• Typical limb features
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
• Mildly short stature
Protruding tongue
Brushfield’s spots apparent in the iris- whitish spots
Social skills often exceed intellectual skills
Intellectual impairment becomes apparent- IQ range form 25 to 70
What are the 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
What are the diagnostic investigations for Down syndrome?
senior paediatrician will discuss their concerns with the parents
• 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 problems 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?
- Refer for a detailed cardiac assessment, hip US and audiology
- Genetic counselling by a clinical geneticist should be offered- it is not necessary to undertake parental chromosome analysis if the cause if non-disjunctional trisomy 21 or mosaic trisomy 21 but this is very important if the karyotype shows a translocation
- Putting parents in contact with a support organization such as Down Association
- Long-term follow up should ideally be by a MDT lead by a paediatrician with special expertise and including a physiotherapist to improve tone and posture
- Routinely test TFT annually
- Refer for audiology and ophthalmic assessment 1-2 yearly
- Almost all children with Down syndrome are now educated in mainstream schools with appropriate 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 the incidence fo Turner syndrome?
Affects 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
