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

@article{Koutsis2018XLC,
  title={X linked Charcot-Marie-Tooth disease and multiple sclerosis: emerging evidence for an association},
  author={Georgios Koutsis and Marianthi Breza and Georgios Velonakis and John Tzartos and Dimitrios S. Kasselimis and Chrisoula Kartanou and Efstratios Karavasilis and Dimitrios Tzanetakos and Maria C Anagnostouli and Elisavet Andreadou and Maria Eleftheria Evangelopoulos and Constantinos Kilidireas and Constantin M. Potagas and Marios Panas and Georgia Karadima},
  journal={Journal of Neurology, Neurosurgery, and Psychiatry},
  year={2018},
  volume={90},
  pages={187 - 194}
}
Objective X linked Charcot-Marie-Tooth disease (CMTX) is a hereditary neuropathy caused by mutations in GJB1 coding for connexin-32, a gap junction protein expressed in Schwann cells, but also found in oligodendrocytes. Four patients with CMTX developing central nervous system (CNS) demyelination compatible with multiple sclerosis (MS) have been individually published. We presently sought to systematically investigate the relationship between CMTX and MS. Methods Over 20 years, 70 consecutive… 
Evidence for Cognitive Deficits in X-Linked Charcot-Marie-Tooth Disease
TLDR
Evidence is provided for cognitive deficits in CMTX caused by mutations in GJB1 coding for connexin-32, found in Schwann cells, but also expressed in oligodendrocytes.
CNS phenotype in X linked Charcot- Marie-Tooth disease
TLDR
The study by Koutsis et al reporting an increased prevalence of multiple sclerosis (MS) in their cohort of patients with X linked Charcot-Marie-Tooth disease (CMTX1) was reviewed to look for a similar association.
Structural and functional brain changes in X-linked Charcot-Marie-Tooth disease: insights from a multimodal neuroimaging study
TLDR
Advanced magnetic resonance (MR) neuroimaging techniques in CMTX patients revealed structural and functional involvement of multiple motor and extra-motor brain areas, which have the potential to delineate the CNS phenotype of a peripheral neuropathy like CMTx.
Recent advances in understanding connexin gap junction pathology in demyelinating diseases
TLDR
The findings show that Cx43 astrocytopathy and Cx47/Cx32 oligodendrogliopathy can be seen in MS, BD and NMOSD and might be associated with disease aggressiveness and distal oligod endocrineopathy in demyelinating conditions.
Whole exome sequencing establishes diagnosis of Charcot–Marie–Tooth 4J, 1C, and X1 subtypes
TLDR
Patients with Charcot–Marie–Tooth hereditary polyneuropathies are diagnosed by whole exome sequencing (WES) following years of fruitless testing.

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TLDR
This work presents a patient with CNS involvement who was previously reported to have Tyr211His mutation affecting the intracellular C-terminal domain of the Cx32 protein, a 24-year-old man who was followed for his polyneuropathy since 1998.
Transient, recurrent, white matter lesions in X-linked Charcot-Marie-Tooth disease with novel connexin 32 mutation.
TLDR
A CMTX family with hereditary demyelinating neuropathy and transient CNS symptoms is presented, in addition to the classic polyneuropathy, transient and reversible white matter lesions on magnetic resonance imaging scans, correlating similarly with transient CNS Symptoms.
Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement
TLDR
The increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.
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TLDR
Four additional patients with Charcot-Marie-Tooth disease with CNS involvement are presented as shown by electrophysiological studies and the presence of myelin lesions in brain MRI.
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TLDR
This is the first female patient with CMTX who showed permanent atypical scattered lesions in cerebral white matter of the brain on T2-weighted magnetic resonance images (MRI), which is very rare.
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TLDR
It is postulate that overexpression of PMP22, the target protein in CMT1A, might influence the immunological self-tolerance to CNS proteins via molecular mimicry, leading to a CNS autoimmune demyelinating disorder.
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TLDR
Four novel mutations of the Cx32 gene are reported in four Greek unrelated families with variable clinical features, closely located to other known mutations associated with CMTX, cosegregate with the disease and are not common polymorphisms.
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TLDR
Animal models of CMT1X demonstrate that loss of C×32 in myelinating Schwann cells causes a demyelinating neuropathy.
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TLDR
Two male patients with CMTX who on separate occasions developed transient ataxia, dysarthria, and weakness within 3 days of returning from ski trips at altitudes above 8,000 feet are considered to be at risk for developing an acute, transient, neurological syndrome when they travel to places at high altitudes and return to sea level.
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