Down's Syndrome

Down’s syndrome is a chromosomal disorder, caused by an error in cell division. People with Down’s syndrome have an extra copy of all or part of chromosome 21 (the smallest human chromosome) in all or some of their body’s cells. Usually cells contain 46 chromosomes (23 from each parent); chromosomes are separate blocks of DNA that are made up of many genes. The chromosomal makeup of the body’s cells is known as the karyotype.

There are 3 types of Down’s syndrome: Trisomy 21, Translocation and mosaicism. 94% of people with Down’s syndrome have trisomy 21, where every cell in their body has a third copy of chromosome 21 (88% of cases originate due to changes in maternal karyotype). Before or during conception, random misdivision of genetic material in either the sperm or egg may cause an extra chromosome in the baby, known as nondisjunction. Scientists do not know what causes this nondisjunction, and there are no known factors which prevent or induce its occurance. However, maternal age has been linked to an increased likelihood of this misdivision occurring in egg cells (for babies born of mothers aged 25, 1 in 1250 will have the condition, whereas for babies born of mothers aged 45, 1 in 30 have Down’s syndrome). 4% of Down’s syndrome is due to translocation, where part of chromosome 21 breaks off during cell division and attached to another chromosome (usually 14) in the cell, known as Robertsonian translocation. Some people with altered genes may not have any symptoms of Down’s syndrome, but instead be carriers. The chance of passing on the condition for male carriers is 1 in 35, and female carriers is 1 in 8, but the majority of people have translocation Down syndrome due to changes at their own conception, not inherited from previous generations. Mosaicism is the least common type of Down’s syndrome (affecting only 2%). In this condition, some of the body’s cells have extra copies of chromosome 21 and others do not, therefore, people with the condition usually have fewer Down’s syndrome symptoms. Down’s syndrome is usually diagnosed at birth, but antenatal screening at the end of the first trimester can also predict whether babies may have Down’s syndrome.

People with Down’s syndrome are generally born with a lower than average birth weight, and as they grow up, may have hypotonia (low muscle tone). Additionally, physical characteristics such as a single crease across the palms, skin folds around the eyes and a flat nasal bridge are more likely in people with Down’s syndrome. Infants with Down’s syndrome may have delayed development in sitting up and walking due to floppiness cause by hypotonia, but this can be helped by stimulation from a young age and physiotherapy to increase the range of movement. Also speech therapy may be needed to help children to learn to speak and some will experience learning difficulties that may require specialist education, though degree of impairment varies greatly between people with the condition. Some children with Down’s syndrome (around 10%) may also have ADHD (attention deficit hyperactivity disorder) or autistic spectrum disorders.

Hearing and/or  vision problems affect 50% of those with Down’s syndrome. Glue ear (build up of fluid in the middle ear) and ear infections are common; difficulties hearing sometimes makes it harder for children to learn or interact with their peers. People with Down’s syndrome are more likely to develop a squint, lazy eye (inability of one eye to focus), eye infections (such as conjunctivitis) or cataracts (clouding of the lens of the eye).  Skin conditions such as dry, flaky skin and thickened skin on the palms of the hands and soles of the feet are not uncommon.

People with Down’s syndrome may have a lowered immunity, and so are susceptible to infection, especially to conditions such as pneumonia. In the past, many people born with Down’s syndrome did not survive childhood, as around 50% have a congenital heart defect, usually a septal defect (a hole in the septum of the heart, which divides the left and right sides) which causes the heart to work harder to pump blood around the body. There is also an increased risk of childhood leukaemia. Intestinal and bowel problems such as constipation, diarrhoea, indigestion and bowel obstruction are common.  Treatment for heart and digestion conditions may require surgery. There has been research into links between Down’s syndrome and dementia (especially the earlier onset of dementia). However the conclusions of studies showed that the proportion of the adult population of those with Down’s syndrome who have dementia is the same as in the adult population without Down’s syndrome.

10% of people with Down’s syndrome have thyroid problems. Often this is hypothyroidism (an underactive thyroid), which results in lack of energy, weight gain, slow reactions and a risk of type 1 diabetes. Related to this, there is a higher than average incidence of obesity amongst those with Down ’s syndrome and Coeliac disease (gluten intolerance) affects around 15% of those with Down’s syndrome, so advice from a dietician may be needed. Rarely, people with Down’s syndrome may suffer from hyperthyroidism (over production of thyroid hormone) leading to hyperactivity and difficulties breathing. Adults with Down’s syndrome tend to have a lowered fertility rate, and so conceiving children is more difficult, the risk of premature birth or miscarriage is also higher.

The prognosis for those born with Down’s syndrome has greatly improved since the 1980s, when the life expectancy was around 25 years, as now people with Down’s syndrome on average will live into their 60s. This is because of better treatment for the conditions associated with Down’s syndrome. Some people with Down’s syndrome are able to become independent adults, whereas others may require support for the rest of their lives.

Recently, scientists at the University of Massachusetts Medical School, have found the possibility of using gene therapy to silence entire chromosomes. In working with the laboratory grown stem cells of a Down’s syndrome patient, and inserting a gene called XIST, the team were able to silence the extra copy of chromosome 21, correcting the growth patterns of the cells. In the future this could have benefits for babies born with Down’s syndrome and other chromosomal disorders, but at the moment this research is still in its infancy.

http://www.nhs.uk/Conditions/Downs-syndrome/Pages/Introduction.aspx
http://downsyndrome.about.com/od/whatcausesdownsyndrome/a/Causeintro_ro.htm
http://www.bbc.co.uk/news/health-23340924