Down's syndrome 15/6/04. By Richard Twyman Down's syndrome is a chromosome disorder – a disease caused by a visible abnormality of the chromosomes rather than a mutation affecting a single gene. In Down's syndrome, the abnormality is a complete extra copy of chromosome 21.

Genetics

The most severe chromosome disorders involve the loss or gain of whole chromosomes. Such abnormalities change the copy number of hundreds or even thousands of genes causing a gross imbalance of the gene products.

The presence of an extra autosome (autosomal trisomy) is usually incompatible with full-term development and results in spontaneous abortion. However, a few trisomics can survive to term because the additional chromosome has relatively few genes (chromosomes 13, 18 and 21, with fewer than 500 genes each). Trisomy 21 is the only autosomal trisomy compatible with a normal lifespan and this may be because chromosome 21 contains only about 240 genes.

Background: Chromosome abnormalities

How does the extra copy of chromosome 21 arise? The most common mechanism is non-disjunction, where the paired chromosomes fail to separate as the cell divides, leaving one cell with two copies and the other with none. If the cell with two copies of chromosome 21 becomes and egg or a sperm, fertilization with a normal gamete will produce an embryo with three copies.

More rarely, one copy of chromosome 21 can become irreversibly attached to another chromosome (translocation Down's syndrome), and in some cases both copies of chromosome 21 can be fused together and behave as a single chromosome.

The incidence of Down's syndrome is about one in 700 live births, but more are found in spontaneous abortions – suggesting the incidence per conception is much higher. The incidence of Down's syndrome is strongly related to maternal age: in young mothers (early 20s), the incidence is one in 1500 but rises sharply to as much as one in 30 by the time the mother is 45. The recurrence risk (the risk of having a subsequent Down's syndrome child if one has already been born) also rises with maternal age and is higher for translocation Down's syndrome, which runs in families.

Symptoms

The symptoms of Down's syndrome include mild to moderate mental retardation, limited growth, characteristic facial features (slanting eyes sometimes with a squint, small ears, open mouth with protruding tongue, small nose) and in about 50 per cent of cases, a simian-like crease across the palm, sometimes accompanied by fused fingers (syndactyly).

The life expectancy of Down's individuals is lower than normal because the disease symptoms often include heart defects (such as ventricular septal defects) and problems with the duodenum and colon.

Two-thirds of Down's conceptions are spontaneously aborted and many individuals with the disease die in childhood. However, life expectancy can be as high as 40-50, and there is no effect on fertility. A small number of children have been born to women with Down's syndrome, about equal numbers of which have been normal and Down's. Older Down's patients are at increased risk of developing Alzheimer’s disease.

Diagnosis

Down's syndrome is generally diagnosed at birth by the facial appearance of affected babies plus the characteristic hypotonia (poor muscle tone, resulting in floppiness), sleepiness and the presence of extra folds of skin around the neck. Blood tests are then carried out to confirm the diagnosis by looking for the extra copy of chromosome 21 or other abnormalities involving this chromosome.

Prenatal testing for Down's syndrome is also possible, and is usually recommended for older mothers and families with a history of translocation Down's syndrome.

Treatment

People with Down's syndrome can lead fulfilling and successful lives. Down's children attend school although they need special education and reach developmental milestones later than unaffected children. Overall, it is important to carry out regular medical checks particularly for heart problems, hearing and visual defects, and skeletal deformation so that appropriate corrective measures can be taken if necessary. Speech therapy and physical therapy can be useful to help Down's children achieve their full potential.