CMTX4 is caused by X-Linked recessive mutations in the AIFM1 gene. Because the AIFM1 gene lives on the X chromosome, this is an X-Linked CMT. CMTX4 is also known as Cowchock Syndrome.
CMTX4 symptom onset can occur anywhere between infancy and early adulthood. CMTers who have CMTX4 can experience a wide range of symptoms including hearing loss, delayed motor development, difficulty walking due to peripheral neuropathy and/or cerebellar ataxia, cognitive impairment, and cerebellar atrophy. Disease severity, however, can be widely variable, and even within the same family. Most CMTers who have CMTX4 tend to develop all features that are associated with CMTX4 though.
CMTX4 is considered a mitochondrial disorder because the AIFM1 gene encodes a mitochondrial function, and the mutation within the gene results in a disruption of that mitochondrial function. Electrodiagnostics show that CMTX4 exhibits axonal neuropathy properties.
A trait that sets all X-Linked CMT apart from the other types of CMT is that there can be no male-to-male transmission. Also, males who have X-Linked CMT tend to be more severely affected than females who have X-Linked CMT.
Homozygous (Female) or Hemizygous (Male)