###### 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/