A Rare Case of Charcot-Marie-Tooth Disease Type 1C With an Unusual Presentation

Abstract

Charcot-Marie-Tooth neuropathy type 1 (CMT1) is an inherited demyelinating neuropathy characterized by distal muscle weakness and atrophy. Charcot-Marie-Tooth disease type 1C (CMT1C) is a rare form of CMT1 caused by mutations in the lipopolysaccharide-induced tumor necrosis factor (LITAF) or small integral membrane protein of the lysosome/late endosome (SIMPLE) gene. Phenotypically, CMT1C is characterized by sensory loss and slow conduction velocity, and is typically slowly progressive and often associated with pes cavus foot deformity and bilateral foot drop. A 42-year-old female presented with a 10-year history of slowly progressive bilateral calf pain and cramps. After multiple electromyography/nerve conduction studies (EMG/NCS) and genetic testing, the patient was revealed to have CMT1C with a heterozygous pathogenic variant, c.334G>A (p.Gly112Ser). However, the presentation of the patient's CMT1C phenotype was unusual compared to patients with similar diagnosis in a previous study, including a normal sensory exam with the exception of high arches and mildly reduced vibratory sense. Additionally, the patient's teenage son already started showing symptoms of CMT1C despite the fact that the onset of the disease typically occurs at an older age. This particular case further highlights the idea that the phenotype related to CMT1C may have a wide spectrum of disease severity.

An exceptional presentation of Charcot–Marie‐tooth 1C disease: Case report of a diagnostic dilemma

“…4 Typically, this phenotype is manifested by distal predominant sensory loss and slow conduction velocity, slow progression, and skeletal deformity. 5 We describe here an unusual presentation of CMT1C with other significant associated features.…”

Variants of uncertain significance in the era of next-generation sequencing

“…Unfortunately, the grandparents of the index patient are deceased, and the mother refused to test. CMT 1С is a rare type of CMT with a prevalence of <1/1,000,000 and could present with classic symptoms of this disorder or a milder clinical presentation (Khosa & Mishra, 2020). This variant is not present in population databases.…”

“…In case 1, both the daughter and her father carried a VUS in a gene associated with CMT type 1 C and demonstrated symptoms related to this disorder. The VUS, found in the LITAF gene, is linked to CMT type 1C, which follows an autosomal dominant type of inheritance (Khosa & Mishra, 2020). Unfortunately, the grandparents of the index patient are deceased, and the mother refused to test.…”

Atypical presentation of Charcot-Marie-Tooth disease type 1C with a new mutation: a case report

“…CMT1C has been described as a symmetrical length-dependent mild form of slowly progressive sensory-motor demyelinating polyneuropathy, and lower limbs are affected more often. The clinical phenotype may differ between individuals even in one family with the same mutation in LITAF [ 4 , 5 ]. The disease in our patient started as subacute asymmetric distal mild weakness and paraesthesia of the right upper limb.…”

“…Patients carrying LITAF mutations may present with either a classical CMT1A phenotype or a sensory phenotype limited to isolated paresthesias [ 4 ]. Recently an atypical course of CMT1C was described as slowly progressive bilateral calf pain and cramps [ 5 ].…”