Jewish Genetics 101
Ashkenazi Jewish Genetic Diseases
A number of genetic disorders occur more frequently in certain ethnic populations. In the Ashkenazi Jewish population (those of Eastern European descent), it has been estimated that one in four individuals is a carrier of one of several genetic conditions. These diseases include Tay-Sachs Disease, Canavan, Niemann-Pick, Gaucher, Familial Dysautonomia, Bloom Syndrome, Fanconi anemia, Cystic Fibrosis and Mucolipidosis IV. Some of these diseases may be severe and may result in the early death of a child. Carrier screening is available for all of these diseases with a simple blood test.
How are these diseases inherited?
In the nucleus of every cell in the body there are 46 chromosomes. Each chromosome is a package that holds many genes. Our genes contain DNA, the set of instructions which makes up who we are. All chromosomes (and the genes that are on those chromosomes) come in pairs. We receive one member of each pair of chromosomes from our mother and the other member of the pair from our father. Sometimes there is a change in a gene (called a mutation) that causes the gene to malfunction.
All of the above-mentioned conditions are inherited in an autosomal recessive manner. This means that an affected person has a change in both genes of the pair of genes, one change inherited from each parent. Neither gene in the pair is working properly, which causes the symptoms of the disease.
A carrier is someone who has a change in only one gene of the pair of genes. Carriers are healthy individuals who are only at risk for passing the gene change on to their children. Most often these diseases occur in families with no prior history of the disease.
What are the diseases?
Tay-Sachs Disease is a condition in which children develop normally until about four to six months of age. It is at this time that the central nervous system begins to degenerate. Individuals with Tay-Sachs Disease lack an enzyme called hexosaminidase (Hex A). The child loses all motor skills and becomes blind, deaf and unresponsive. Death usually occurs by the age of four. The carrier rate in the Ashkenazi Jewish population is approximately 1 in 25. More rare than the infantile type is Late Onset Tay-Sachs Disease, where the progression of symptoms is slower and milder.
Canavan Disease is very similar to Tay-Sachs Disease, with normal development until age two to four months, followed by progressive loss of previously attained skills. Most individuals with Canavan Disease die by the age of five. An estimated 1 in 40 Ashkenazi Jews is a carrier for this disease.
Niemann-Pick Disease – Type A is a disease in which a harmful amount of a fatty substance accumulates in different parts of the body. Failure to thrive and a progressive neurodegenerative course lead to death by three years of age. The carrier rate in the Ashkenazi Jewish population is approximately 1 in 90.
Gaucher Disease – Type 1 (pronounced go-shay) is a variable condition, both in age of onset and in progression of symptoms. A painful, enlarged and overactive spleen, with anemia and low white blood cell count are usually the initial features of Gaucher Disease. Bone deterioration is a major cause of discomfort and disability. Approximately 1 in 14 Ashkenazi Jews is a carrier of this condition. Treatment is available.
Familial Dysautonomia (FD) is a disease that causes the autonomic and sensory nervous systems to malfunction. This affects the regulation of body temperature, blood pressure, stress response, normal swallowing and digestion. An estimated 1 in 30 Ashkenazi Jews is a carrier of FD.
Bloom Syndrome is characterized by short stature, sun-sensitive facial skin lesions, an increased susceptibility to infections and a higher incidence of leukemia and certain cancers. The carrier rate is about 1 in 100 in the Ashkenazi Jewish population.
Fanconi anemia – Type C is a disease associated with short stature, bone marrow failure and a predisposition to leukemia and other cancers. Some children may have learning difficulties or mental retardation. Approximately 1 in 89 Ashkenazi Jews is a carrier for this condition.
Mucolipidosis IV (ML IV) is caused by the accumulation of certain harmful substances throughout the body. Individuals with ML IV experience a range of levels of motor and mental retardation, with developmental delays often manifesting themselves as early as the first year of life. Other symptoms can be related to the eyes, such as corneal clouding, pseudostrabismus and retinal degeneration.
Cystic Fibrosis (CF) is a multi-system disorder that causes the body to produce a thick mucus. The mucus accumulates primarily in the lungs and the digestive tract, resulting in chronic lung infections and poor growth. CF does not affect intelligence. The carrier rate for CF among all Caucasian individuals is approximately 1 in 25. The CF carrier test has a detection rate of 97% in the Ashkenazi Jewish population.
What if we both are carriers?
If two carriers of the same disorder have children, there is a 25% chance of having an affected child, a 50% chance of having a child who is a carrier like themselves, and a 25% chance of having a child who is neither affected nor a carrier. If an individual is found to be a carrier, genetic counseling is available at many clinics throughout the country to discuss the implications of this finding. If partners are found to be carriers of the same disorder(s), a genetic counselor can provide information and support, which may be helpful in making important family planning decisions.
The results of these tests are highly accurate. However, there is a slight possibility that someone who tests negative for being a carrier could still be a carrier. There may be rare mutations that DNA testing may not pick up.