Down's Syndrome Flashcards
What is Down’s Syndrome also known as?
Trisomy 21
What is meant by Trisomy 21
The patient has three copies of chromosome 21
Is the extra copy of 21 a full or partial copy?
Can be either
How common is Down’s Syndrome compared to other autosomal trisomies?
It is the most common
How common is Down’s Syndrome in terms of causes of severe learning difficulties?
It is the most common
What can the extra chromosome 21 occur as a result of?
Non-disjunction, translocation or mosaicism
What is the most common cause the extra chromosome 21?
Meiotic nondisjunction
How many cases of Trisomy 21 are due to meiotic nondisjunction?
94%
What happens in meiotic nondisjunction?
Chromosome 21 fails to separate leaving one gamete with 2 and on game with none
In order for Down’s Syndrome to occur in meiotic non-disjunction, which gamete must be fertilised?
The one with two chromosome 21 copies
What increases the likelihood of meiotic non-disjunction in the maternal gamete?
Increasing maternal age?
Can meiotic non disjunction occur in spermatogenesis?
Yes
What does meiotic non-disjunction during spermatogenesis mean?
That the abnormal gamete can be of paternal origin
What percentage of Down’s Syndrome cases are caused by translocation?
5%
What is a Robertson translocation?
When the extra chromosome 21 is joined onto another chromosome
Do all people with Robertson translocation present with symptoms?
No, some are phenotypically normal carriers
What test is recommended due to the ability for phenotypically normal carriers to exist?
Parental chromosomal analysis
What percentage of Down’s Syndrome is caused by mosaicism?
1%
What is mosaicism?
Where some cells are normal and some have trisomy 21
How does mosaicism usually arise?
Zygote is chromosomally normal but non-disjunction occurs during mitosis
What is sometimes the case in patient with mosaicism forms of trisomy 21?
The phenotype is milder
What is the main risk factor for development of Down’s syndrome?
Older mother
What are the main signs of Down’s Syndrome?
- Characteristic craniofacial appearance
- Short neck
- Single palmar crease
- Incurved and short 5th finger
- ‘Sandal gap’ between 1st and 2nd toes
- Hypotonia
What are the characteristic craniofacial features of Down’s Syndrome?
- Round face
- Flat nasal bridge
- Upslanted palpebral fissures
- Epicanthic folds
- Brushfield spots in iris
- Small mouth and protruding tongue
- Small ears
- Flat occiput and third fontanelle
How is Down’s Syndrome often picked up?
Antenatal screening
What are all pregnant women offered with regards to antenatal screening for Down’s Syndrome?
- Blood biochemical marker tests
- USS to look for nuchal thickening
What are women with an identified increased risk offered?
Amniocentesis
What does amniocentesis allow?
Checking of fetal karyotype
What are becoming increasingly available to allow early detection of Down’s Syndrome in pregnancy?
Non-invasive karyotyping techniques
What should happen if there is clinical suspicion of Down’s Syndrome following birth?
A senior paediatrician should discuss this with the parents
How should a post-birth diagnosis of Down’s Syndrome be confirmed?
Chromosome analysis
What technique can be used to analyse chromosomes after birth?
Interphase FISH
What is another trisomy that should be considered when diagnosing Down’s Syndrome?
Trisomy 18
What is trisomy 18 also known as?
Edward’s Syndrome
What other conditions should be considered as differentials for Down’s Syndrome?
- Multiple X Syndrome
- Zellweger syndrome
What further testing should children with Down’s Snydrome be referred for following birth?
- Detailed cardiac assessment
- Hip ultrasound
- Audiology
What is the role of a clinical geneticist in the management of Down’s Syndrome?
Genetic counselling
What may be useful to help parents cope with their child being diagnosed with Down’s Syndrome?
Access to support organisations e.g. Down Association
In the long-term how are patients with Down Syndrome continued to be managed?
- Follow-up by MDT
- Physiotherapy
- Annual TFT
- Audiology and ophthalmic assessment every 1-2 years
What is the main cause of early death in Down’s Syndrome?
Congenital cardiac diseases
Excluding congenital cardiac diseases, what is the life expectancy of a person with Down’s Syndrome?
Well into adult life
What do most patient’s with Down Syndrome develop by their 40’s?
Alzheimer’s
What is the effect of most patient’s with Down Syndrome developing Alzheimer’s by their 40’s?
Life expectancy is somewhat shortened from average
How do the majority of patient’s with Down Syndrome live in adult life?
Semi-independently with supervision
What congenital diseases are associated with Down’s Syndrome?
- Congenital heart defects
- Duodenal atresia
- Hirschsprung’s
What percentage of patient’s with Down’s Syndrome have congenital heart defects?
40%
What percentage of patient’s with Down’s Syndrome have Hirschsprung’s?
~1%
What later medical problems may a person with Down’s Syndrome be at increased risk of developing?
- Delayed motor milestones
- Learning difficulties
- Short stature
- Increased susceptibility to infections
- Otitis media w/ effusion
- Visual problems
- Increased risk of leukaemia and solid tumours
- Acquired hip dislocation
- Atlantoaxial instability
- Obstructive sleep apnoea
- Hypothyroidism
- Coeliac disease
- Epilepsy
- Early onset Alzheimer’s
What percentage of patient’s with Down’s Syndrome develop otitis media with effusion?
75%
What is the consequence of otitis media with effusion?
Hearing impairment
What effect may hearing impairment have on development?
Slow, especially speech
What visual impairments may develop in Down’s Syndrome?
- Cataracts
- Squints
- Myopia
What percentage of patient’s with Down’s Syndrome develop cataracts?
15%
What percentage of patient’s with Down’s Syndrome develop myopia?
50%
What percentage of patient’s with Down’s Syndrome develop obstructive sleep apnoea?
50-75%
What percentage of patient’s with Down’s Syndrome develop hypothyroidism?
15%
