Inheritance Patterns and CMT
Knowing which of the forms of CMT you have is important so that you can understand the implications for passing the disorder on to your children. The many different forms of CMT are inherited in different ways, so genetic counseling will vary depending on your form of CMT and its mode of inheritance.
There are three distinct inheritance patterns that encompass all the many variations of CMT.
Autosomal Dominant Inheritance
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The most common forms of CMT are inherited in an autosomal dominant pattern. Autosomal means that the mutation occurs on a chromosome other than the X or Y chromosome. An affected person has one normal gene and one CMT gene in the relevant pair and each child has a 50/50 chance of inheriting the abnormal or CMT gene, giving them the disorder. Either boys or girls have an equal chance of inheriting the disease in this inheritance pattern. In this form, affected children can pass the CMT gene to their children, but unaffected children do not have the abnormal gene in their DNA and cannot pass CMT to their children.
Autosomal Recessive Inheritance
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The least common formsof CMT are inherited in an autosomal recessive manner. All Type 4 patients have inherited the autosomal recessive form of CMT. In autosomal recessive forms, both parents have to be “carriers” of the defective gene before a child can be affected. Neither parent shows signs of any symptoms of CMT, but the child who inherits autosomal recessive CMT gets a double dose of the defective gene causing him or her to have the disease, usually in a more severe form. Two parents each with an autosomal recessive CMT gene have a 1 in 4 chance of passing it on to their children. It can affect both males and females.
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The final form of inheritance is called X-linked. In this form, the faulty CMT gene is carried on the female sex chromosome. The disease is inherited by males from their mothers, who are carriers. The mother will typically have no symptoms at all or be mildly affected. Each of her sons will have a 50 percent chance of having CMT, and an affected son is likely to be more severely affected than his mother. Each of her daughters has a 50 percent chance of being a carrier.
A male affected with X-linked CMT cannot pass the disorder to his sons, but all of his daughters will be carriers of the disorder. Unaffected children cannot pass the disorder onto their children since they don’t carry the gene.
It is also possible for CMT to develop as a result of a new mutation or spontaneous mutation. These cases are called “de novo” or the new case of CMT in a family. A child who is a new mutation case can then pass the defect on to his/her children.
Genetic Testing and Counseling
Since researchers have found many of the genes and mutations that cause CMT, they have been able to develop genetic tests that offer people information about their specific diagnosis. People consider genetic testing for a variety of reasons. One reason is to confirm a tentative diagnosis of CMT, since early symptoms of CMT can mimic those of other disorders. Another reason for a person with clear signs of CMT to have genetic testing is to enable other family members to determine if they are affected and help them make decisions regarding family planning.
Advice about genetic testing and genetic counseling can be found through the National Society of Genetic Counselors on the Internet at www.nsgc.org. Choose the resource link to find a genetic counselor near you.