Genetics condition

What is Tay-Sachs disease?

Tay-Sachs disease is a rare inherited disorder that causes progressive destruction of nerve cells in the brain and spinal cord (the central nervous system).

The most common form of Tay-Sachs disease begins in infancy. Infants with this disorder typically appear normal until the age of 3 to 6 months, when development slows and muscles used for movement weaken. Affected infants lose motor skills such as turning over, sitting, and crawling. They also develop an exaggerated startle reaction to loud noises. As the disease progresses, children with Tay-Sachs disease experience seizures, vision and hearing loss, mental retardation, and paralysis. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Children with this severe infantile form of Tay-Sachs disease usually survive only into early childhood.

Other forms of Tay-Sachs disease are much rarer. Signs and symptoms can begin in childhood, adolescence, or adulthood and are usually milder than those seen with the infantile form of Tay-Sachs disease. As in the infantile form, mental abilities and coordination are affected. Characteristic features include muscle weakness, loss of muscle coordination (ataxia) and other problems with movement, speech problems, and mental illness. These signs and symptoms vary widely among people with late-onset forms of Tay-Sachs disease.

How common is Tay-Sachs disease?

Tay-Sachs disease is very rare in the general population. The genetic mutations that cause this disease are more common in people of Ashkenazi (eastern and central European) Jewish heritage than in those with other backgrounds. In recent years, however, screening for mutations and genetic counseling have made the condition much less frequent in this population.

The genetic mutations that cause Tay-Sachs disease are also more common in certain French-Canadian communities of Quebec, the Old Order Amish community in Pennsylvania, and the Cajun population of Louisiana.

What genes are related to Tay-Sachs disease?

Mutations in the HEXA gene cause Tay-Sachs disease.

The HEXA gene provides instructions for making part of an enzyme called beta-hexosaminidase A, which plays a critical role in the central nervous system. This enzyme is located in cellular structures called lysosomes, which are the cell's recycling centers. Within lysosomes, beta-hexosaminidase A helps break down a fatty substance known as GM2 ganglioside. Mutations in the HEXA gene disrupt the activity of beta-hexosaminidase A, preventing the breakdown of this substance. As a result, it can accumulate to toxic levels in the brain and spinal cord. Progressive damage caused by the buildup of GM2 ganglioside leads to the destruction of nerve cells, which causes the signs and symptoms of Tay-Sachs disease.

Because Tay-Sachs disease impairs the function of a lysosomal enzyme and involves the buildup of GM2 ganglioside, this condition is sometimes referred to as a lysosomal storage disorder or a GM2-gangliosidosis.

Read more about the HEXA gene.

What is Down syndrome?

Down syndrome is a chromosomal condition that is associated with mental retardation, a characteristic facial appearance, and poor muscle tone (hypotonia) in infancy. People with this condition are at an increased risk for heart defects, digestive problems such as gastroesophageal reflux or celiac disease, hearing loss, and cancer of blood-forming tissue (leukemia). Additionally, some people with Down syndrome have reduced activity of the thyroid gland (hypothyroidism). The thyroid gland is a butterfly-shaped organ in the lower neck that produces hormones.

Some evidence indicates that Down syndrome is associated with an increased risk of Alzheimer disease, a degenerative disease of the brain that causes a gradual loss of memory, judgment, and ability to function. Although Alzheimer disease is usually a disorder of late adulthood, in people with Down syndrome the signs and symptoms can appear as early as age 30.

How common is Down syndrome?

Down syndrome occurs in 1 in 800 to 1,000 births. The risk of having a child with Down syndrome increases as a woman gets older.

What are the genetic changes related to Down syndrome?

Down syndrome is related to chromosome 21.

Most cases of Down syndrome result from trisomy 21, which means each cell in the body has three copies of chromosome 21 instead of the usual two copies. The extra genetic material disrupts the normal course of development, causing the characteristic features of Down syndrome. Although the connection between Down syndrome and Alzheimer disease is unclear, researchers believe that an extra copy of a particular gene on chromosome 21, the APP gene, may account for the increased risk.

A small percentage of Down syndrome cases occur when only some of the body's cells have an extra copy of chromosome 21. These cases are called mosaic Down syndrome.

Although uncommon, Down syndrome also can occur when part of chromosome 21 becomes attached (translocated) to another chromosome before or at conception. Affected people have two copies of chromosome 21, plus extra material from chromosome 21 attached to another chromosome. These cases are called translocation Down syndrome.

Read more about chromosome 21.

Can Down syndrome be inherited?

Most cases of Down syndrome are not inherited, but occur as random events during the formation of reproductive cells (eggs and sperm). An error in cell division called nondisjunction results in reproductive cells with an abnormal number of chromosomes. For example, an egg or sperm cell may gain an extra copy of chromosome 21. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra chromosome 21 in each of the body's cells.

Mosaic Down syndrome is also not inherited. It occurs as a random error during cell division early in fetal development. As a result, some of the body's cells have the usual two copies of chromosome 21, and other cells have three copies of the chromosome.

Translocation Down syndrome can be inherited. An unaffected person can carry a rearrangement of genetic material between chromosome 21 and another chromosome. This rearrangement is called a balanced translocation because there is no extra material from chromosome 21. Although they do not have signs of Down syndrome, people who carry this type of balanced translocation are at an increased risk of having children with the condition.