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Genetics

Down syndrome is caused by having three copies of the genes on chromosome 21, rather than the usual two.The parents of the affected individual are typically genetically normal. Those who have one child with Down syndrome have about a 1% risk of having a second child with the syndrome, if both parents are found to have normal karyotypes.

The extra chromosome content can arise through several different ways. The most common cause (approximately 92–95% of cases) is a complete extra copy of chromosome 21, resulting in trisomy 21. In 1 to 2.5% of cases, some of the cells in the body are normal and others have trisomy 21, known as mosaic Down syndrome. The other common mechanisms that can give rise to Down syndrome include: a Robertsonian translocation, isochromosome, or ring chromosome. These contain additional material from chromosome 21 and occur in approximately 2.5% of cases. An isochromosome results when the two long arms of a chromosome separate together rather than the long and short arm separating together during egg or sperm development.

Trisomy 21

Translocation Trisomy 21 (also known by the karyotype 47,XX,+21 for females and 47,XY,+21 for males) is caused by a failure of the 21st chromosome to separate during egg or sperm development. As a result, a sperm or egg cell is produced with an extra copy of chromosome 21; this cell thus has 24 chromosomes. When combined with a normal cell from the other parent, the embryo and baby has 47 chromosomes, with three copies of chromosome 21. About 88% of cases of trisomy 21 result from non separation of the chromosomes in the mother, 8% from non-separation in the father, and 3% after the egg and sperm have merged.^[48]

The extra chromosome 21 material may also occur due to a Robertsonian translocation in 2–4% cases. In this situation, the long arm of chromosome 21 is attached to another chromosome, often chromosome 14. In a male affected with Down syndrome it results in a karyotype of 46XY,t(14q21q). This may be a new mutation or previously present in one of the parents. The parent with such a translocation is usually normal physically and mentally; however, during production of egg or sperm cells there is a higher chance of creating reproductive cells with extra chromosome 21 material. This results in a 15% chance of having a child with Down syndrome when the mother is affected and a less than 5% risk if the father is affected. The risk of this type of Down syndrome is not related to the mother's age. Some children without Down syndrome may inherit the translocation and have a higher risk of having children of their own with Down syndrome. In this case it is sometimes known as familial Down syndrome.

Efforts such as early childhood intervention, screening for common problems, medical treatment where indicated, a good family environment, and work related training can improve the development of children with Down syndrome. Education and proper care can improve quality of life. Raising a child with Down syndrome is more work for parents than raising a non effected child. Typical childhood vaccinations are recommended.

Health screening

A number of health organizations have issued recommendations for screening those with Down syndrome for particular diseases. It is recommended that this be done systematically.

At birth all children should get an electrocardiogram and ultrasound of the heart. Surgical repair of heart problems may be required as early as three months of age. Heart valve problems may occur in young adults, and further ultrasound evaluation may be needed in adolescents and in early adulthood. Due to the elevated risk of testicular cancer, some recommend checking the person's testicles yearly.

Cognitive development

Hearing aids or other amplification devices can be useful for language learning in those with hearing loss. Speech therapy may be useful and it is recommended that it be started around 9 months of age. As those with Down's typically have good hand eye coordination, learning sign language may be possible. Augmentative and alternative communication methods, such as pointing, body language, objects, or pictures are often used to help with communication even though there is little concrete evidence. Behavioral issues and mental illness are typically managed with counseling and/or medications.

Education programs before reaching school age may be useful. School-age children with Down syndrome may benefit from inclusive education (whereby students of differing abilities are placed in classes with their peers of the same age) provided that some adjustments are made to the curriculum. Evidence to support this however is not very strong. In the United States the Individuals with Disabilities Education Act of 1975 requires that public schools generally allow attendance by students with Down's.

Other

Tympanostomy tubes are often needed and often more than one set during the person's childhood. Tonsillectomy is also often done to help with sleep apnea and throat infections. Surgery, however, does not always address the sleep apnea and a continuous positive airway pressure (CPAP) machine may be useful. Physical therapy and participation in physical education may improve motor skills. Evidence to support this in adults, however, is not very good.

Efforts to prevent respiratory syncytial virus (RSV) infection with human monoclonal antibodies should be considered, especially in those with heart problems. In those who develop dementia there is no evidence for memantine, donepezil, rivastigmine, or galantamine.

Many alternative medical techniques are used in Down syndrome; however, they are poorly supported by evidence. These include: dietary changes, message, animal therapy, chiropractics and naturopathy, among others. Some proposed treatments may also be harmful.