X-linked Charcot-Marie-Tooth disease type 1 (CMTX1)
General description
X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is a hereditary motor and sensory neuropathy (HMSN) that belongs to the broader group of Charcot-Marie-Tooth diseases (CMT), a heterogeneous set of inherited neuropathies. Traditionally, CMT is classified into two main types: a demyelinating form (CMT1) and an axonal form (CMT2). However, CMTX1, an X-linked dominant subtype, exhibits both demyelinating and axonal characteristics.
CMTX1 is caused by mutations in the gap-junction beta-1 gene (GJB1) on chromosome Xq13.1, which encodes the gap-junction protein connexin-32. This protein is primarily localized in myelinated peripheral nerves, where it facilitates ion and small molecule diffusion across the myelin sheath. Although CMTX1 primarily affects the peripheral nervous system, a minority of patients also exhibit central nervous system (CNS) involvement.
Clinically, CMTX1 is characterized by a slowly progressive weakness and atrophy of distal muscles, reduced or absent deep tendon reflexes, sensory abnormalities, and foot deformities such as pes cavus and hammer toes. It accounts for approximately 10%–15% of hereditary motor and sensory neuropathy cases and represents about 90% of X-linked Charcot-Marie-Tooth disease cases. Additionally, some patients experience transient CNS symptoms and reversible cerebral white matter lesions, though the mechanisms underlying these manifestations remain unclear.
References
- U-King-Im, J. M., et al. "MRI findings in X-linked Charcot–Marie–Tooth disease associated with a novel connexin 32 mutation." Clinical radiology 66.5 (2011): 471-474.
T2WI and FLAIR hyperintensity
Brain MRI findings in this case exhibit symmetrical signal abnormalities and restricted diffusion, primarily affecting the parietal and occipital white matter, as well as the splenium and genu of the corpus callosum. The involvement extends to the middle cerebellar peduncles and the corticospinal tracts.