###### Created: 2023-01-30 16:46
###### Areas & Topics: #medicine #disability
###### Note Type: #permanent
###### Connected to: [[Learning Disabilities]]
### Definition
- Down Syndrome is a genetic condition caused by trisomy 21 (having an additional copy of the 21st chromosome).
- It was first described by the English physician John Langdon Down in 1866, but its association with chromosome 21 was established almost 100 years later by Dr. Jerome LeJeune in Paris.
- The main risk factor for Down Syndrome is increasing maternal age.
### Epidemiology
- Down Syndrome is the most common chromosomal abnormality amongst liveborn children and humans in general.
- Its incidence increases with maternal age and varies amongst population (approximately 1 in 300 to 1 in 1000).
- Around 50% to 75% of foetuses with Downs Syndrome die before term, but it is still the chromosomal abnormality with the highest birth survival rate .
- This high percentage of survival of patients with trisomy 21 is thought to be a function of a small number of genes on chromosome 21 called Hsa21, which is the smallest and least dense of the autosomes.
### Aetiology
- The most common cause of DS is **nondisjunction of chromosome 21** **during meiosis** on the maternal side resulting in trisomy 21.
All causes of Down Syndrome include:
- Trisomy 21: In most cases (94% to 95%), trisomy 21 occurs due to nondisjunction (i.e. failure of the two 21 chromosomes to separate) during meiosis and in 90% to 95% of cases the additional chromosome is inherited from the mother
- Robertsonian translocation: 3% to 4% of Down Syndrome is caused by the translocation of the long arm of chromosome 21 to another chromosome, typically chromosome 14
- Trisomy 21 mosaicism: Where an issue in fertilisation leads to a population of cells having trisomy 21 and a population of cells having 46 chromosomes.
### Clinical Features
Down Syndrome leads to characteristic facial features and affects a variety of organ systems.
#### Head, Neck and Limb Features
Head and Neck Features
- Brachycephaly (flattening of the back of the skull)
- Epicanthal Folds (a fold of skin over the top of the eye which leads to slanted looking eyes)
- Upward-slanting palpebral fissures (the line between the the medial and lateral canthus slanting upward towards the ears)
- Flat facial profile
- Small open mouth
- Protruding tong
- Small low-set dysplastic (abnormally formed) ears
- Short neck with excess skin
Limb Features
- Short, broad hands
- Singular transverse palmar crease
- Clinodactyly (a finger which curves to one side, typically the pinky)
- Joint hyperflexibility
- Wide gap between first and second toes (also known as a sandal gap).
![[B9781437711554001176_f117-001-9781437711554.jpg]]
![[1558-1525256440987.png]]
#### Organ System and General Features
Intellectual Disability
- Most people with Down Syndrome will have a degree of intellectual disability, usually mild to moderate.
- A delay in reaching developmental milestones is also commonly seen.
Dementia
- Early-onset Alzheimer's-like dementia is common in those with Down Syndrome.
- By the age of 40 neuropathological changes are seen in virtually all patients.
Cardiac Disease
- Around 40-50% of people with DS have a congenital heart disease (CHD).
- The most common CHD seen is typically an atrioventricular septal defect.
Fertility and Reproductive Organs
- Impaired spermatogenesis means males with Down Syndrome are rarely fertile.
- Women can be but may have issues with subfertility or premature menopause limiting the time they are fertile.
Growth
- People with Down Syndrome are commonly of a shorter stature and are more likely to be overweight or obese.
### Sources
https://app.pulsenotes.com/specialities/paediatrics/notes/down-syndrome
https://www.nhs.uk/conditions/downs-syndrome/
https://www.ncbi.nlm.nih.gov/books/NBK526016/