The Genetics and Inheritance
of Wilson's Disease

The Genetics of Wilson's Disease

Wilson's disease occurs throughout the world in all races and nationalities. It affects 1 in 30,000 people. It is transmitted as an autosomal recessive disease, which means it is not sex-linked (it occurs equally in men and women). In order to inherit the disease, each of one's parents must carry a Wilson's disease gene, which each passes to the affected child. The responsible gene is located at a precisely known site on chromosome 13. The gene is called ATP7B.

Many cases of Wilson's disease occur due to spontaneous mutations in the gene. A significant number of other cases are simply transmitted from generation to generation.

More than 30 different mutations have been identified thus far. It has, therefore, been difficult to devise a specific genetic screening test for the Wilson's disease. However, if the precise mutation is identified in a particular family, a genetic diagnosis is possible. This may help in identifying symptom-free but affected relatives so that they may be treated before they become ill or handicapped. Someday a genetic test may help in prenatal diagnosis.

People with only one abnormal gene are called carriers (heterozygotes). They may have mild, but medically insignificant, abnormalities of copper metabolism. They do not become ill and do not need treatment.

Wilson's Disease Inheritance

As mentioned previously, Wilson's disease is inherited as a recessive disease. This means a patient must receive an abnormal gene from each parent. The disease only occurs if a person inherits two abnormal genes. If both parents carry the Wilson's disease gene, the chance of their child developing Wilson's disease is 25%.

Genetic Detail:

• 1 in 100 individuals in the general population carries the Wilson's disease gene. Carriers have one normal and one abnormal gene.
• 100% of a patient's children will receive a Wilson's disease gene.
• 50% of a carrier's children will receive the Wilson's disease gene, since the carrier has one normal and one abnormal gene.
  

Siblings of Wilson's disease patients have a 25% chance of having the disease.

• If both parents are carriers, each of their children has a 1 in 4 chance of getting Wilson's disease, 2 in 4 chance of being a carrier, and a 1 in 4 chance of being normal.

Children of patients have 1 in 200 chance of having the disease.

• A patient's children have a 100% chance of inheriting one abnormal gene. The other (normal) parent has 1 in 100 chance carrying the gene, and 1/2 the time he or she will pass it on.

Grandchildren of patients have a 1 in 400 chance of having the disease.

• A patient's grandchildren have a 50% chance of inheriting a gene (1 in 2) since all the patient's children are carriers. From the other parent, a grandchild has a 1 in 200 chance of inheriting the gene (1/2 x [1/2 x 1/100] from the normal spouse = 1/400).

Nieces and nephews of patients with Wilson's disease have a 1 in 600 chance of having the disease.

• 2 in 3 of unaffected siblings carry the gene. The risk of a couple both being carriers is 2/3 x 1/100 = 1/150, and the risk of each of their children having the disease is 1/4 x 1/150 = 1/600.

Cousins have a 1 in 800 chance of having the disease.

• 50% of a patient's aunts and uncles are carriers. Therefore 1/2 x 1/100 = 1/200 couples are both carriers, and 1/4 of their children will be affected = 1/800.

Screening

The most accurate screening test is 24-hour urine measurement of copper. Blood ceruloplasmin testing is helpful, but levels are normal in 5% - 10% of Wilson's disease patients. A special eye exam can detect Kayser-Fleischer rings, which are diagnostic of Wilson's disease. However, these rings do not have to be present for a person to have Wilson's disease. These rings may be invisible to the naked eye. For unaffected (symptom-free) relatives, a urine test should be done at about age 5 and again at age 15. Screening can begin for low ceruloplasmin and abnormal liver functions at age 2.

All siblings, aunts, uncles, children, nieces, nephews, and cousins of Wilson's disease patients should be tested. People with Wilson's disease may not have any signs, symptoms, or evidence of illness. However, all of them will always become seriously ill and eventually die if they are not treated. Testing is simple and safe, and excellent treatments are available.
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