Systematic review of CMTX1 patients with episodic neurological dysfunction

Abstract

ObjectiveX‐linked Charcot‐Marie‐Tooth type 1 (CMTX1) is an inherited peripheral neuropathy caused by mutations in the gap junction beta 1 (GJB1) gene, which encodes the connexin32 protein. A small number of patients with GJB1 mutations present with episodic neurological dysfunction and reversible white matter lesions, which has not been adequately reported. Here, we aim to enable clinicians to further understand this particular situation through systematically reviewing all published relevant cases.MethodsWe conducted a comprehensive search of the PubMed electronic database for medical literature relevant to CMTX1 patients with episodic neurological dysfunction and then fully analyzed the general information, clinical manifestations, and characteristics of magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and nerve conduction study (NCS).ResultsWe identified 47 cases of CMTX1 associated with episodic central nervous system (CNS) dysfunction from 38 publications. CMTX1 patients experienced episodic CNS deficits at a young age, ranging from infancy to 26 years, and 45 (95.7%) of them were male. The CNS symptoms manifested as facial, lingual, or limb weakness in 44 (93.6%), dysarthria or dysphagia in 39 (83.0%), facial or limb numbness in 15 (31.9%), and ataxia in 10 (21.3%) patients. The duration of episodic symptoms ranged from 3 minutes to 6 months. Thirty (63.8%) CMTX1 cases have reported obvious predisposing factors, among which the most common factors were infection or fever (27.7%), travel to high altitude (12.8%), and intensive exercise (8.5%). As for brain MRI, most abnormal signals were found in bilateral deep white matter (88.9%) and corpus callosum (80.0%). In addition, most of the NCS results were abnormal, including prolonged latency, reduced amplitude, and slowed conduction velocity. The motor nerve conduction velocity (MNCV) of median nerve was the most detectable and valuable, ranging from 25 to 45 m/s.InterpretationWe have reported the most comprehensive summary of the demographic and clinical profile from 47 CMTX1 patients with episodic CNS deficits and provided new insight into the phenotype spectrum of CMTX1. We hope that our study can help clinicians make early diagnosis and implement the best prevention and treatment strategies for CMTX1 patients with episodic CNS deficits.

X-linked Charcot-Marie-Tooth disease after SARS-CoV-2 vaccination mimicked stroke-like episodes: A case report

“…The most common predisposing factors for CMTX1 are infection or fever, high-altitude travel, and intense exercise[ 13 ]. However, this patient did not have any of these predisposing factors before the onset.…”

Novel mutations in GJB1 trigger intracellular aggregation and stress granule formation in X-linked Charcot-Marie-Tooth Disease

“…GJB1 mutations may lead to reversible PNS phenotype in CMT1X as well as CNS abnormality. The CNS manifestations of CMT1X primarily include episodic limbs or facial weakness, facial or limb numbness, dysarthria or dysphagia, ataxia, spasticity, hyperreflexia, and cognitive impairment (Niu et al, 2019 ; Tian et al, 2021 ). All four probands in the present study shared a similar phenotype of early-onset, slowly progressive distal muscle weakness, decreased or absent tendon reflex, and pes cavus.…”

Phenotypic Variability and Diagnostic Characteristics in Inherited Peripheral Neuropathy in Latvia

“…CMTX1 patients can exhibit CNS involvement with relapsing-remitting neurologic symptoms. There are controversial data pertaining to evidence of cognitive impairment prevalence and decreased volume of white matter in patients with CMTX1 (Chanson et al, 2013;Daniel et al, 2019;Tian et al, 2021).…”