CMTX5 is caused by X-Linked recessive mutations in the PRSP1 gene. Because the PRSP1 gene lives on the X chromosome, this is an X-Linked CMT.
X-Linked recessive mutations in the PRPS1 gene also cause ARTS (OMIM 301835) and X-Linked Deafness 1, or DFNX1 (OMIM 304500). There is significant symptom overlap between CMTX5, ARTS, and DFNX1, and there can also be significant disease severity variability within the same family. Some scientists have argued that CMTX5, ARTS, and DFNX1 would be best described as, together, representing a phenotypic spectrum. Others have argued that, because of the syndromic nature of CMTX5, it should not be considered a type of CMT because CMT is not syndromic.
CMTX5 symptom onset usually occurs in early childhood. CMTers who have CMTX5 will usually experience lower leg weakness and atrophy beginning in early childhood, accompanied by a progressive loss of vision caused by optic nerve atrophy. CMTers who have CMTX5 will usually experience significant atrophy and weakness of the intrinsic muscles of the hands leading to significant finger contractures. Deafness in early adulthood is not uncommon with CMTX5. A condition called Retinitis Pigmentosa (OMIM 268000) has also been reported with CMTX5.
CMTX5 nerve conduction characteristics are consistent with an axonal CMT. CMTX5 almost always includes optic nerve atrophy and deafness in addition to the manifestations of polyneuropathy that are typical of CMT. But, not every CMTer who has CMTX5 will experience optic or hearing impairment.
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)