CMT is inheritable because the genetic mutations that cause CMT, whatever those mutations might be, are inheritable. The chances of your children inheriting CMT depend solely on the specific underlying genetic mutation. How CMT is passed on/inherited is referred to as an inheritance pattern, and CMT has five of these patterns. To describe these, we’ll first cover the basic terminology.
In genetics and inheritance, autosomal refers to any gene that lives on a numbered chromosome (1-22)—the autosomes. Dominant refers to a gene needing/having one mutation. Recessive refers to a gene needing/having two mutations. X-Linked refers to any gene that lives on an X-chromosome. Mitochondrial refers to a mutation in a gene that is found only in mitochondrial DNA. Y-Linked refers to a gene that lives on the Y-chromosome (there are no Y-Linked CMT subtypes at present time).
What is autosomal dominant inheritance? In autosomal dominant inheritance, the gene lives on an autosome, and the gene has just one CMT-causing mutation. The majority of CMT subtypes (89 subtypes) are inherited in an autosomal dominant pattern. Somebody who has an autosomal dominant CMT subtype has a 50/50 chance of passing on their CMT to each of their children, regardless of gender and regardless of their children’s gender.
What is autosomal recessive inheritance? In autosomal recessive inheritance, the gene lives on an autosome and the gene has two CMT-causing mutations. There are 69 CMT subtypes that are inherited in an autosomal recessive pattern. Because these subtypes are caused by having two mutations within the gene and having only one of the needed mutations does not cause CMT, these subtypes are more rare than autosomal dominant subtypes, as a whole.
We normally have two copies of every gene, with only a few exceptions. When somebody has an autosomal recessive CMT subtype, they have a CMT-causing mutation in both copies of the associated gene. When somebody has an autosomal recessive CMT subtype, they likely inherited one of their two CMT-causing mutations from one parent, and the other mutation from the other parent. Each parent likely had only one mutation each, having only one mutation in this context does not cause CMT (this is different than autosomal dominant CMT), and each likely were not aware they even had this one mutation until after their child was diagnosed. In this situation, there was a 25% chance of inheriting both CMT-causing mutations.
Somebody who has an autosomal recessive CMT subtype will pass on one of their two CMT-causing mutations to each of their children, regardless of gender and regardless of their children’s gender. They cannot pass on both of their CMT-causing mutations. Their children, however, will not have CMT. They won’t have CMT because they will have inherited only one of the needed two CMT-causing mutations.
What is X-Linked inheritance? In X-Linked dominant inheritance, the gene lives on the X-chromosome and has one CMT-causing mutation. In X-Linked recessive inheritance, the gene has two CMT-causing mutations. Chromosomal females (X-X) who have X-Linked CMT, whether X-Linked dominant or X-Linked recessive, have the same chances of passing on their CMT-causing genetic mutation as though the subtype was autosomal dominant or autosomal recessive. Chromosomal males (X-Y), however, will not and cannot pass on their X-Linked CMT-causing mutation to any of their sons but they will pass it onto every daughter. This difference between chromosomal females and chromosomal males who have X-Linked CMT owes itself to chromosomal females having two X-chromosomes, chromosomal males having only one X-chromosome, and chromosomal males passing on their Y-chromosome only to their sons while passing on only their X-chromosome to their daughters.
Because chromosomal males have only one X-chromosome and therefore only one copy of the genes that live on the X-chromosomes, X-Linked dominant and X-Linked recessive inheritance terminology isn’t used. Instead, in the context of chromosomal males, the patterns combine into a single X-Linked inheritance description.
What is mitochondrial inheritance? In mitochondrial inheritance, the genes found in mitochondrial DNA are passed only from a chromosomal female to her children. There is only one CMT subtype caused by a mutation in a gene found only in mitochondrial DNA (ATP6-associated CMT). If a chromosomal male has this CMT subtype, his children will not inherit it from him. But, if a chromosomal female has this subtype, each of her children will inherit it from her. There is some research that suggests chromosomal males do pass on mitochondrial DNA to their children, but the research, at this time, is not conclusive.
