Autosomal Aneuplodies ✅ Flashcards
What is true of most autosomal aneuploidies?
They are fatal in utero
Which autosomal aneuploidies are survivable to term?
- Trisomy 13
- Trisomy 18
- Trisomy 21
What autosomal aneuploidy has the most favourable outcome?
21 (Down’s syndrome)
Why does trisomy 21 have the most favourable outcome?
Because chromosome 21 has fewer genes than other chromosomes
Why does chromosome 21 have fewer genes than other chromosomes?
It is short and has low gene density
What is trisomy 13 known as?
Patau syndrome
What % of babies with Patau syndrome die in the first month?
50%
What is the prognosis of babies that survive the first month with Patau syndrome?
Most die in the first year
What are the common features of Patau syndrome?
- Polydactyly
- Cardiac abnormalities
- Midline abnormalities of the head and face
What midline abnormalities of the head and face are common in Patau syndrome?
- Closely-spaced eyes, single central eye (cyclopia)
- Midline cleft lip and palate
- Holoprosencephaly
What is holoprosencephaly?
When brain does not divide properly into left and right hemispheres
What happens to most babies with Edwards syndrome?
They die within the first year of life
What happens to children who survive the first year of life with Edwards syndrome?
They make little developmental progress
What are the features of Edwards syndrome?
- Dysmorphic features
- Poor growth antenatally and postnatally
- Small head
- Cardiac and renal abnormalities
Describe the dysmorphic features of Edwards syndrome?
They may be subtle, and can include;
- Ear anomalies
- Clinodactyly
- Overlapping fingers
- Micrognathia
- Rocker-bottom feet
Why is Downs syndrome an important condition?
It is the only autosomal trisomy frequently associated with survival into adulthood
What is often a feature of Downs syndrome babies at birth?
They are often hypotonic
What are the dysmorphic features of Downs syndrome?
- Epicanthic folds
- Upslanted palpebral fissures
- Protruding tongue
- Sandal gap
- Brushfield’s spots in the iris
- Single palmar crease
What organ systems are often abnormal in Downs syndrome?
- Cardiac
- Gastrointestinal
What cardiac abnormalities are common in Downs syndrome?
- Atrioventricular septal defect (AVSD)
- Ventricular septal defect (VSD)
What GI abnormalities are common in Downs syndrome?
- Duodenal atresia
- Hirschsprung’s disease
How severe are the learning difficulties in Downs syndrome?
Mild to moderate
Is behaviour problematic in Downs syndrome children?
Often is in older children
What are the long-term problems associated with Downs syndrome?
- Short stature
- Obesity
- Increased risk of leukaemia and solid tumours
- Increased risk of Alzheimers
What % of cases of Down’s syndrome is caused by non-disjunction?
95%
What is the risk of recurrence of Down’s syndrome caused by non-disjunction?
1%, or the mother’s age related risk, whichever is higher
What % of cases of Down’s syndrome are mosaic?
2%
What is the recurrence rate of mosaic Down’s syndrome?
Low
How does the presentation of mosaic Down’s syndrome differ from in other causes?
The phenotype is often milder
What % of cases of Down’s syndrome are caused by an unbalanced Robertson translocation?
2%
What are the types of Robertsonian translocations causing Down’s syndrome?
- 14/21 or 21/22
- 21/21
What is the risk of recurrence of Down’s syndrome in another child when the cause is a 14/21 or 21/22 Robertsonian translocation?
10% if the mother is carrying the translocation
2.5% if the father is carrying the translocation
What is the risk of recurrence of Down’s syndrome in another child when the cause is a 21/21 translocation?
100%
Why is there a higher risk of recurrence in another build when Down’s syndrome is caused by an unbalanced Robertsonian translocation?
Because parents may carry a balanced translocation, which can result in unbalanced transmission
What it is important to differentiate between when determining the recurrence rate of Down’s syndrome?
Conventional trisomy 21 occurring as a result of non-disjunction from that caused by unbalanced Robertsonian translocation
How can the genetic cause of Down’s syndrome be determined?
Karyotyping or FISH analysis
How does karyotyping or FISH analysis determine the cause of Down’s syndrome?
By directly visualising the chromosomes
What is not useful in determining the recurrence risk of Down’s syndrome?
Parental microarray
Ovarian function testing
Skin biopsy for chromosomal mosaicism
Clinical features
Why is parental microarray not useful in determining the recurrence risk of Down’s syndrome?
It will not detect a balanced translocation
