A Review of X-linked Charcot-Marie-Tooth Disease

Abstract

X-linked Charcot-Marie-Tooth disease (CMTX) is the second common genetic variant of CMT. CMTX type 1 causes 90% of CMTX. The most important clinical features of CMTX are similar with other types of CMT; however, a few patients get the central nervous system involved with or without white matter lesions; males are more severely and earlier affected than females. In this review, the authors focus on the origin and classification of CMTX, the central nervous system manifestations of CMTX1, the possible mechanism by which GJB1 mutations cause CMT1X, and the emerging therapeutic strategies for CMTX. Moreover, several cases are presented to illustrate the central nervous system manifestations.

Clinical and Genetic Features of Chinese X-linked Charcot-Marie-Tooth Type 1 Disease

“…Patients with an earlier onset before 10 years old or in infancy were rare in the present study and other reports. [222627] Electrophysiological findings of our patients further confirmed that CMT1X is an intermediate neuropathy.…”

X linked Charcot-Marie-Tooth disease and multiple sclerosis: emerging evidence for an association

“…In fact, there is evidence that these transient WMLs do not involve demyelination, as suggested by increases rather than decreases in magnetisation to transfer ratio during the acute phase 7. The comprehensive list documented in the review by Wang and Yin43 includes a case with atypical small scattered WMLs, but no CNS symptoms, which resembles the second of our ‘other notable cases’ 44…”

“…A recent review has comprehensively documented the vast majority of CMTX cases with CNS involvement reported in the literature 43. It includes two of the four cases reporting inflammatory CNS demyelination compatible with a diagnosis of MS 15 18.…”

“…We could not identify other cases fulfilling MS diagnostic criteria. The vast majority of cases had transient CNS symptoms lasting usually a few hours, bilateral symmetric white matter hyperintensities, absence of gadolinium enhancement, no evidence of CSF oligoclonal bands and evidence of WML resolution within a few months, whenever checked 43. In fact, there is evidence that these transient WMLs do not involve demyelination, as suggested by increases rather than decreases in magnetisation to transfer ratio during the acute phase 7.…”

Fits, feet and HIV: lessons from a case of coexisting epilepsy and neuropathy in a patient with perinatally acquired HIV-1 infection

“…CMT is a demyelinating peripheral neuropathy characterised by distal muscle weakness, atrophy and sensory loss, frequently associated with foot deformity and foot drop,3 and affects approximately 10–80 per 100 000 individuals worldwide and 12 per 100 000 individuals in England 4. Individuals usually develop symptoms between 5 and 25 years.…”