What is Down syndrome?

Down syndrome (also called Trisomy 21) is a genetic disorder that occurs in approximately 1 of 800 live births. It is the leading cause of cognitive impairment. Down syndrome is associated with mild to moderate learning disabilities, developmental delays, characteristic facial features, and low muscle tone in early infancy. Many individuals with Down syndrome also have heart defects, leukemia, early-onset Alzheimer's disease, gastro-intestinal problems, and other health issues. The symptoms of Down syndrome range from mild to severe. Life expectancy for individuals with Down syndrome has dramatically increased over the past few decades as medical care and social inclusion have improved. A person with Down syndrome in good health will on average live to age 55 or beyond. Down syndrome is named after Doctor Langdon Down, who in 1866 first described the syndrome as a disorder. Although Doctor Down made some important observations about Down syndrome, he did not correctly identify what causes the disorder. It wasn't until 1959 that scientists discovered the genetic origin of Down syndrome.

What are the chromosome basics of Down syndrome?

Genes on an extra copy of chromosome 21 are responsible for all characteristics associated with Down syndrome. Normally, each human cell contains 23 pairs of different chromosomes. Each chromosome carries genes, which are needed for proper development and maintenance of our bodies. At conception, an individual inherits 23 chromosomes from the mother (through the egg cell) and 23 chromosomes from the father (through the sperm cell). However, sometimes a person inherits an extra chromosome from one of the parents. In Down syndrome, an individual most often inherits two copies of chromosome 21 from the mother and one chromosome 21 from the father for a total of three chromosomes 21. Because Down syndrome is caused by the inheritance of three chromosomes 21, the disorder is also called trisomy 21. About 95% of individuals with Down syndrome inherit an entire extra chromosome 21. Approximately 3% to 4% of individuals with Down syndrome do not inherit an entire extra chromosome 21, but just some extra chromosome 21 genes, which are attached to another chromosome (usually chromosome 14). This is called a translocation. Most of the time, translocations are random events during conception. In some instances however, a parent is a balanced carrier of a translocation: The parent has exactly two copies of chromosome 21, but some of the genes are distributed to another chromosome. If a baby inherits the chromosome with the extra genes from chromosome 21, then the child will have Down syndrome (two chromosomes 21 plus extra chromosome 21 genes attached to another chromosome).

About 2% to 4% of people with Down syndrome inherit additional genes from chromosome 21, but not in every cell of the body. This is known as mosaic Down syndrome. These individuals may, for example, have inherited extra genes from chromosome 21 in their muscle cells, but not in any other type of cell. Because the percentage of cells with extra genes from chromosome 21 varies in people with mosaic Down syndrome, they often don't have all the typical physical characteristics and may not be as severely intellectually impaired as people with full trisomy 21. Sometimes, mosaic Down syndrome is so mild that it will go undetected. On the other hand, mosaic Down syndrome can also be misdiagnosed as trisomy 21, if no genetic testing has been done.

How do the extra genes lead to Down syndrome?

Exactly how the extra genes from chromosome 21 lead to Down syndrome is still not clear. Scientists believe that the increased presence of specific genes alters the interaction between these and other genes. Some genes will become more active and others less active than normal, leading to changes in the development and maintenance of the body. Why some individuals are more severely affected than others might have to do with how many and which specific extra genes were inherited. Scientists are trying to find out which genes from chromosome 21, when present in three copies, are responsible for the different characteristics of Down syndrome. Currently, about 400 genes on chromosome 21 have been identified, but the functions of most are still unknown. Through human studies and animal models, scientists are making progress in understanding the functions of individual genes.

What are the risk factors for conceiving a child with Down syndrome?
The only well known risk factor for conceiving a child with Down syndrome is advanced maternal age. The older the woman is at conception, the greater the risk of having a child with Down syndrome. Mother's age at conception Risk of Down syndrome

25 years 1 in 1,250 30 years 1 in 1,000 35 years 1 in 400 40 years 1 in 100 45 years 1 in 30

Parents who have conceived a child with Down syndrome have a 1% increased risk of conceiving another child with Down syndrome. If a parent is a carrier of a chromosome 21 translocation, the risk can be as high as 100%.

Women with Down syndrome have a 50% risk of conceiving a child with Down syndrome. If the father has Down syndrome, the risk of conceiving a child with Down syndrome is also increased.

What are the characteristic features and symptoms of Down syndrome?

Although the severity of Down syndrome ranges from mild to severe, most individuals with Down syndrome have widely recognizable physical characteristics. These include:

a flattened face and nose, a short neck, a small mouth sometimes with a large, protruding tongue, small ears, upward slanting eyes that may have small skin folds at the inner corner (epicanthal fold);

white spots (also known as Brushfield spots) may be present on the colored part of the eye (iris);

the hands are short and broad with short fingers, and with a single crease in the palm;

poor muscle tone and loose ligaments are also common; and

development and growth is usually delayed and often average height and developmental milestones are not reached.

What type of prenatal screening is available for Down syndrome?

Several noninvasive screening options are offered to parents. If Down syndrome is suspected due to the screening outcome, a formal diagnosis can be made before the baby arrives. This gives parents time to gather information about Down syndrome before their baby is born and to make arrangements in case of medical complications. Prenatal screening tests currently available include the expanded alpha-fetoprotein (AFP) screening test, the nuchal translucency test, and additional ultrasound screens which look for changes in certain anatomical features of the fetus. While these screening tests can assess the risk for Down syndrome, they cannot confirm Down syndrome with certainty. The most widely used screening test is the AFP. Between weeks 15 and 20 of pregnancy, a small blood sample is taken from the mother and examined. The levels of AFP and three hormones called unconjugated estriol, human chorionic gonadotropin, and inhibin-A are measured in the blood sample. If the AFP and hormone levels are altered, Down syndrome can be suspected, but not confirmed. Likewise, a normal test result does not rule out Down syndrome.

The nuchal translucency test measures the thickness of the fold in the neck via ultrasound. This test can be done between 11 and 13 weeks of pregnancy. In combination with the mother's age, this test identifies about 80% of Down syndrome fetuses. Women considered at high risk (advanced maternal age, positive AFP test, or a history of a previous child with Down syndrome) may benefit from additional ultrasound scans between 18 and 22 weeks of pregnancy. When certain anatomical features are altered, absent, or present in a fetus, it may indicate Down syndrome. Some of the markers that are examined include:

the length of the long arm (humerus) or leg bone (femur), the length of the nasal bridge, the size of the renal pelvis (hypoplasia, pyelectasis), small bright spots in the heart (echogenic intracardiac foci), small middle section of the little finger (hypoplastic fifth digit), a large gap between the first and second toe, increased brightness of the bowel (echogenic bowel), and pelvic bone angle (widened iliac angle).

How is the diagnosis of Down syndrome made?

The diagnosis of Down syndrome can be made before birth using one of several diagnostic tests. These tests carry a small risk of miscarriage. If Down syndrome is suspected after a child is born, a diagnosis can be made via chromosome analysis. Amniocentesis is performed between 16 and 20 weeks of pregnancy. During this procedure, a thin needle is inserted through the abdominal wall and a small sample of amniotic fluid is taken. The sample is analyzed for chromosome anomalies. Chorionic villus sampling (CVS) is done between 11 and 12 weeks of pregnancy. It involves the collection a chorionic villus cell sample from the placenta either through insertion of a needle in the abdominal wall or through a catheter in the vagina. The chromosomes in CVS are analyzed for deviations. For percutaneous umbilical blood sampling (PUB), fetal blood is taken from the umbilical cord using a needle inserted through the abdominal wall. The blood sample is examined for chromosome abnormalities. It is usually performed after week 18.

What about cognitive impairment in Down syndrome?

The most common condition associated with Down syndrome is cognitive impairment. Cognitive development is often delayed, and all individuals with Down syndrome have mild to severe learning difficulties that last throughout their lives. How the extra chromosome 21 leads to cognitive impairment is not entirely clear. The average brain size of a person with Down syndrome is small and scientists have found alterations in the structure and function of certain brain areas such as the hippocampus and cerebellum. Particularly affected is the hippocampus, which is responsible for learning and memory. Scientists are using human studies and animal models of Down syndrome to find out which specific genes on the extra chromosome 21 lead to different aspects of cognitive impairment. Heart conditions Apart from cognitive impairment, the most common medical conditions associated with Down syndrome are congenital heart defects. About half of all people with Down syndrome are born with a heart defect, often with an atrioventricular septal defect. Other common heart defects occurring in Down syndrome include ventricular septal defect, atrial septal defect, tetralogy of Fallot, and patent ductus arteriosus. Some babies will require surgery shortly after birth to correct these heart defects. Gastrointestinal conditions Gastrointestinal conditions are also commonly associated with Down syndrome, especially esophageal atresia, tracheoesophageal fistula, duodenal atresia or stenosis, Hirschsprung disease, and imperforate anus. Individuals with Down syndrome are at a higher risk for developingceliac disease. Corrective surgery is sometimes necessary for gastrointestinal problems. Cancer Certain types of cancer are more frequently found in Down syndrome, such as acute lymphoblastic leukemia (a type of blood cancer), myeloid leukemia, and testicular cancer. Solid tumors on the other hand rarely occur in this population. Other conditions Other medical conditions include:

hearing loss, frequent ear infections (otitis media), underactive thyroid (hypothyroidism), cervical spine instability, visual impairment,

sleep apnea, obesity, constipation, infantile spasms, seizures, dementia, and early-onset Alzheimer's disease.

About 18% to 38% of individuals with Down syndrome have coexisting psychiatric or behavior conditions, such as:

autism spectrum disorders, attention deficit hyperactivity disorder (ADHD), depression, stereotypical movement disorders, and obsessive compulsive disorder.

How is Down syndrome managed?

Although the genetic cause of Down syndrome is known, there is currently no cure. Due to advances in technology, scientists are slowly beginning to understand which genes when present in three copies are responsible for which Down syndrome characteristics, but it will take many years to fully grasp the complex interplay between the different genes. Much research to date is focused on understanding the causes of impaired cognition in Down syndrome and on finding potential therapies that might improve learning. Most of these studies are carried out using animal models of Down syndrome, but some human clinical trials involving potential therapies are also being conducted. Corrective surgery for heart defects, gastrointestinal irregularities, and other health issues is necessary for some individuals. Regular health checkups should be scheduled to screen for other conditions such as visual impairments, ear infections, hearing loss, hypothyroidism, obesity, and other medical conditions. Individuals with Down syndrome should be fully included in family and community life.

What about early intervention and education for Down syndrome?

It is very important to stimulate, encourage, and educate children with Down syndrome from infancy. Programs for young children with special needs are offered in many communities. Early intervention programs, including physical therapy, occupational therapy, and speech therapy can be very helpful.

What are the needs of infants and preschool children with Down syndrome?
Like all children, children with Down syndrome greatly benefit from being able to learn and explore in a safe and supportive environment. Being included in family, community, and preschool life will help a child with Down syndrome develop to his or her full potential. While social development and social learning are often quite good, development in other areas such as motor skills, speech, and language are usually delayed. Many children with Down syndrome eventually reach most developmental milestones, but mild to severe learning difficulties will persist throughout life. In general, children with Down syndrome are more prone to illnesses, and vision and hearing impairments, which can contribute to the child's learning difficulties. Regular health checkups are very important. Some children may have more severe developmental delays. This could be due to coexisting medical or psychiatric conditions such as seizures, autism, or ADHD.

How do adolescents with Down syndrome develop?

Adolescents with Down syndrome undergo the same hormonal changes during pubertyas typically developing children. Girls with Down syndrome have regular menstrual periods and should receive instructions on hygiene. Although women with Down syndrome are not very fertile, they can become pregnant. Men with Down syndrome have low sperm count, but in some cases have fathered children. Proper education regarding sexual development and contraception is very important.

What should one expect for adults with Down syndrome?

Individuals with Down syndrome live longer than ever before. Due to full inclusion in society, many adults with Down syndrome now live semi-independently, enjoy relationships, work, and contribute to their community. Adults with Down syndrome also age faster than average. The older they become, the higher the risk of developing hypothyroidism, late-onset seizures (tonic-clonic seizures in particular), memory loss, and dementia. By age 40, many individuals with Down syndrome will show signs of dementia and early-onset Alzheimer's disease. By age 60, 50% to 70% of adults will develop Alzheimer's disease. Why individuals with Down syndrome age prematurely and why they develop Alzheimer's disease is not entirely clear. At least one gene (the amyloid precursor protein) on chromosome 21 is thought to be involved in Alzheimer's disease. Since individuals with Down syndrome have three copies of this gene, it is likely that this gene contributes to the increased occurrence of Alzheimer's disease in this population.

Detecting dementia and early signs of Alzheimer's disease is a challenge in individuals with Down syndrome who are often already cognitively impaired. It is important for caregivers and doctors to be aware of changes in skills necessary for independence.

Do individuals with Down syndrome work?

While some individuals with Down syndrome find suitable paid employment, many others are volunteers, or hold no job. Individuals with Down syndrome who wish to work should receive adequate training and support. This is not always readily available in all communities at present. In addition, employers should be made more aware of the benefits of employing someone with Down syndrome.

Where can I find clinical trials for Down syndrome?

Down Syndrome Clinical Trials

Down Syndrome At A Glance

Down syndrome is a genetic disorder and the most common cause of cognitive impairment.

Individuals with Down syndrome have characteristic physical features that are widely recognized.

Down syndrome is associated with heart defects, gastrointestinal conditions, and other health issues.

Individuals with Down syndrome are at a high risk for developing dementia and earlyonset Alzheimer's disease.

The only well known risk factor for conceiving a child with Down syndrome is advanced maternal age.

Screening for and diagnosis of Down syndrome is possible before birth.

Due to improved medical treatment and social inclusion, the average life span of an individual with Down syndrome is now more than 55 years.

Individuals with Down syndrome often live very healthy and productive lives.

http://www.medicinenet.com/down_syndrome/