Down's Syndrome

Overview

Down’s syndrome (DS) is an inborn (congenital) condition caused by an extra copy or piece of chromosome 21 in all or most of the affected person’s cells. Several birth defects and complications arise from an error in cell division that occurs before, or shortly after conception. This error has a widespread effect on the physical and mental development of the affected person.

Chromosomes hold genetic information. Most cells contain 22 pairs of chromosomes and a 23rd set of either XX (in females) or XY (in males) for a total of 46 chromosomes. Reproductive cells (eggs and sperm) contain a single set of 23 chromosomes that combine when an egg is fertilised to form a new set of 46 in the foetus (half from each parent). In most cases of Down’s syndrome, an extra copy of chromosome 21 is present in either the egg or sperm. This is caused by a defect in the production of an egg or sperm cell which, although occurring infrequently, happens more often as a person gets older. The extra copy of chromosome 21 becomes part of the fertilised egg and is replicated in all of the embryo’s cells. This form of Down’s syndrome is called trisomy 21, and it accounts for about 95% of cases.

The error may also occur after conception, in the developing embryo. As the foetus grows, some cells may have 47 chromosomes, while others have 46. This form of Down’s syndrome is called mosaic trisomy 21.

In another rare form of Down’s syndrome called translocation trisomy 21, a piece of chromosome 21 attaches to another chromosome before or at conception. Even though the foetus has 46 chromosomes, it still has an extra portion of chromosome 21 in its cells. All individuals with additional chromosome 21 genetic material, regardless of the cause, will develop some of the features of Down’s syndrome.

Before the advent of screening, about 1 in 800 babies in the United Kingdom were born with Down’s syndrome. The chance of having an affected baby increases significantly as a woman gets older. It increases from less than 1 in 1,000 in women under 30 to 1 in 400 by age 35 and to 1 in 12 by the time a woman is 49 years old. However, since more younger women become pregnant, the majority of those with Down’s syndrome, about 75%, will be born to women under 35. There are many characteristic features associated with Down’s syndrome. Not every child will have every one and the degree to which they are affected may vary greatly. Features include:

  • A small head with small, low-set ears
  • Slanting eyes, a broad flat face, and a short nose
  • A small mouth and protruding tongue
  • Short, small but broad hands and feet and a single crease across the palm
  • Short fingers and an abnormal bone in the little finger
  • Reduced muscle tone (hypotonia)
  • Very flexible joints
  • Instability of the top of the spine)
  • Mild to moderate mental limitations

Complications of Down’s syndrome vary greatly. Some may be present at birth, some may arise during childhood, others during adulthood, and others may never be experienced. Doctors and family members must be aware of these potential complications as patients may or may not be able to clearly communicate their symptoms and/or may express them in unexpected ways. Complications can include:

  • Coeliac disease
  • Dental disease
  • Developmental delays
  • Diabetes
  • Food sensitivities and constipation
  • Gut abnormalities and obstructions (5 to 10%)
  • Hearing loss (75%)
  • Heart defects and disease (close to 50%)
  • Increased incidence of ear infections, colds, bronchitis, tonsillitis, and pneumonia
  • Increased risk of acute leukaemia
  • Premature aging, loss of mental abilities, and Alzheimer’s type symptoms in patients under 40 years of age
  • Seizure disorders
  • Sleep apnoea (50 to 75%)
  • Spinal cord compression
  • Thyroid disease (about 15%)
  • Visual problems, including cataracts (about 60%)
Tests

Tests for Down’s syndrome may be undertaken at different times and for different purposes. Testing during pregnancy may be undertaken to screen for Down’s syndrome, diagnose it and offer counselling about the choices during pregnancy and detect any malformations that will require medical interventions shortly after birth. A person with Down’s syndrome will have tests to monitor the condition throughout his or her life. Testing is usually a combination of laboratory and non-laboratory evaluations.

Laboratory Tests
Screening and diagnostic tests may be done during a woman’s pregnancy, in either the first or the second trimester. Screening tests are not diagnostic; they indicate an increased likelihood of the foetus having Down’s syndrome. Department of Health policy in England recommends that all pregnant women be offered Down’s syndrome screening tests. Prenatal diagnostic tests may be offered when screening tests indicate a higher risk of an affected pregnancy. They involve taking samples of the fluid or tissues surrounding the baby and testing for an additional copy or portion of chromosome 21. A very small risk of infection and miscarriage is associated with these diagnostic tests. Diagnostic testing performed after birth involves taking a sample of blood from the baby and evaluating his or her chromosomes. Tests that detect the complications often seen in those with Down’s syndrome are used to help diagnose conditions that arise and to monitor the effectiveness of treatment. Some of the complications, such as congenital heart defects and bowel obstructions, may be present at birth. Others such as hearing loss, vision disorders, leukaemia, and thyroid disease may develop at any time during the person’s life.

Testing includes:

Prenatal screening

  • 1st trimester screen - An ultrasound test for nuchal translucency ( see below) and a blood test forpregnancyassociated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (hCG). Although the blood may be taken for testing after 10 weeks of pregnancy, the ultrasound test should only be performed after 11 weeks 2 days.
  • 2nd trimester screen (triple/quad testing) - Blood is tested for alpha fetoprotein (AFP), free beta or total hCG, and unconjugated oestriol (uE3) for the triple test. For the quad test inhibin A is also measured.These tests are performed between 14 weeks toad 20 weeks gestation.

Prenatal diagnosis

Foetal cells are examined for an extra copy of chromosome 21 from a sample taken by:-

  • Placental sampling, known as Chorionic Villus Sampling (CVS), from about the 10th week of pregnancy
  • Sampling of fluid from the sac around the baby, known as Amniocentesis, usually after 15 weeks of pregnancy
  • Cord blood sampling through the skin, known as Percutaneous Umbilical Blood Sampling (PUBS), performed between 18 to 22 weeks of pregnancy

Diagnosis after birth

  • Chromosomes from a blood sample taken after birth are evaluated for an extra copy of chromosome 21. The presence and type of Down’s syndrome can be determined from this test.

Non-Laboratory Tests Prenatal

  • Nuchal translucency (NT) is an ultrasound measurement of the space between the foetal spine and the skin at the back of the neck. In a foetus with Down‘s syndrome, there may be an increased amount of space. Specialised training is needed to perform this test and interpret the results.
  • 2nd trimester ultrasound  may help monitor foetal development and detect malformations such as cardiac and gastrointestinal defects.

At or soon after birth

  • Echocardiogram and chest x-rays are used to detect cardiac defects.
  • Ultrasound and magnetic resonance imaging are used to evaluate any suspected congenital conditions such as heart defects and bowel obstructions.
  • Hearing evaluation
Treatments

Currently there is no way to prevent or cure Down’s syndrome. Prenatal screening and diagnosis are performed to detect the condition in the foetus and to allow the pregnant woman and her family to make informed choices. Early diagnosis allows the family and doctor to work together to monitor the baby and to prepare for complications that may require attention shortly after birth. Medical treatments may include surgical interventions, such as repairing heart defects and bowel obstructions, and starting medications for conditions such as thyroid disease.

In individuals with Down’s syndrome, careful monitoring, prompt attention to acute and chronic conditions that arise, and “early intervention” to maximize the health of the individual are important. The complications and abilities of people with Down’s syndrome will vary widely. It is not possible to determine early in a child’s life what they will be able to learn, do, and accomplish. They should be given encouragement and stimulation from an early age, follow a healthy diet, and take regular physical activities to maintain muscle strength. Families should work closely with specialists to develop life enhancing and treatment plans that meet the unique needs of those affected.

There are national and local initiatives and resources that can help children with Down’s syndrome develop their physical, communication, and learning skills. Many children will be able to join regular classes in schools, participate in sports, and as adults hold jobs and live semi-independent lives. Most will be able to live relatively normal and healthy lives. The average lifespan of those with Down syndrome has increased in recent years with most living to the mid 50’s, and many into the 60’s and 70’s.