Down’s syndrome or Trisomy 21 is a chromosomal disorder caused by the presence of all, or part of, an extra chromosome 21.
Clinical Features
A neonate with Down’s syndrome usually shows marked hypotonia, small ears, up-slanting palpebral fissures, flat facial profile and brachycephaly. Additional features include epicanthic folds, short nose, depressed nasal bridge and protruding tongue. There may be a single palmar crease, and wider than normal gap between the big and second toe.
There is a high (40-50%) incidence of congenital cardiac defects such as ventricular septal defect, patent ductus arteriosus and atrioventriculoseptal defect. Other congenital malformations such as duodenal atresia and Hirschsprung Disease are also much more common.
Milestones are delayed, and IQ lower than average, but there is a wide range, from profound mental disability to only mild disability. There is a trend towards integration of children with Down’s syndrome into mainstream education with additional support, although this is not always appropriate. Adults can often achieve a degree of independence but usually still require some support.
Life expectancy is reduced (median age at death is 49 yrs). Congenital heart disease is a major factor in increased mortality in infancy and childhood. Most people with Down’s syndrome who survive into their 40s and 50s begin to suffer from an Alzheimer’s-like dementia.
Individuals with Down’s syndrome are prone to a number of other medical conditions including hypothyroidism, leukaemia, atlanto-axial instability, epilepsy, hearing deficits, immune deficiencies and gastroesophageal reflux. GPs can have a valuable part to play by offering regular medical checks to adults with Down’s syndrome, in order to detect easily treatable conditions such as deafness and hypothyroidism.
See Guidelines For Annual Review of Adults with Down’s Syndrome.
Fertility amongst men and women with Down’s syndrome is reduced. Men are usually unable to father children, whilst women show significantly reduced rates of conception. Approximately half of the offspring of someone with Down’s syndrome will also have the syndrome themselves.
Genetics
Trisomy 21(47,XX,+21) This is the cause of approximately 95% of Down’s syndrome and is caused by a nondisjunction event during meiosis of the gamete. During nondisjunction, a gamete (sperm or egg) is produced with an extra copy of chromosome 21. When combined with a normal gamete from the other parent, the embryo now has 47 chromosomes, with three copies of chromosome 21.
Robertsonian Translocation
The extra chromosome 21 material that causes Down’s syndrome may be due to a Robertsonian translocation in one of the parents. This is the cause of 2-3% of Down’s syndrome. In this case, the long arm of chromosome 21 is attached to another chromosome. The parent with such a translocation will be phenotypically normal, but during meiosis they have a significant chance of producing a gamete with extra chromosome 21 material. If Down’s syndrome is due to a Robertsonian translocation in one of the parents then there is a significant risk that future pregnancies will also be affected.
Mosaicism
This is the cause of 1-2% of Down’s syndrome. Mosaicism is where some of the cells in the body have the usual pattern of 46 chromosomes but other cells have the extra chromosome 21. Individuals with mosaicism still have some features of Down’s syndrome but their learning difficulties are not as severe.
Incidence and Recurrence Risk
The incidence of Down’s syndrome increases strikingly with maternal age with an approximate chance of 1 in 32 at term in mothers age 45 yrs or older.
See table of age related chance for Down’s Syndrome
There is a high incidence of spontaneous fetal loss particularly early in pregnancy. Recurrance rates tend to be low except in the case of Robertsonian translocations and mosaisicism. For this reason karyotyping of the individual with Down’s syndrome is essential to determine the genetic basis (i.e trisomy 21, Robertsonian translocation or mosaicism). If a sibling, aunt or uncle has Down’s syndrome due to trisomy 21, there are no increased chance to the patient arising from this.
Prenatal Screening
Prenatal screening is possible by way of blood tests and nuchal fold thickness. Prenatal diagnosis is possible by chorionic villus sampling (CVS) or amniocentesis.
Information
Here are some useful websites:
