A Rare Phenotype of Uncommon Charcot–Marie–Tooth Genotypes Complicated With Inflammation Evaluated by Genetics and Magnetic Resonance Neurography

Abstract

The pathogenesis of Charcot–Marie–Tooth (CMT) disease, an inherited peripheral neuropathy, is associated with more than 60 nuclear genes. We reported a rare phenotype of the uncommon CMT genotype complicated with neuroinflammation, that is, an MPZ mutation, NC_000001.11 (NM_000530.6): c.308G > C detected by next-generation sequencing. Moreover, we present a case of the CMT type 1B, with atypical presentation as two patterns of hypertrophy in the brachial and lumbosacral plexus, as well as enhancement in the cauda equina and nerve roots on multimodal magnetic resonance neurography (MRN). MRN assessment facilitated the identification of coexisting neuroinflammation and provided more evidence, especially for patients with atypical symptoms in hereditary sensory and motor neuropathy, who could benefit from immunotherapy.

Charcot–Marie–Tooth Disease with Myelin Protein Zero Mutation Presenting as Painful, Predominant Small-Fiber Neuropathy

“…In particular, it has been suggested that the manifestations and the course of the disease in some patients are modified by a superimposed autoimmune/inflammatory response, possibly driven by the changed immunogenicity of an abnormal MPZ protein, in keeping with the experimental observations of secondary autoimmunity and CIDP-like manifestations in P0 knockout mice [41,42]. In some patients, consistent features of an acute/subacute onset [20], rapidly progressive [43] or stepwise-fluctuating course [19,44,45], elevation of cerebrospinal fluid protein [19,20,22,[44][45][46], and response to immunotherapies [22,[44][45][46] were described, including cases with painful neuropathy. Other comorbidities potentially influencing the neuropathy expression, such as diabetes or B12 deficiency that are often associated with painful neuropathy, are not mentioned in the case studies.…”