A TRPV4 mutation caused Charcot-Marie-Tooth disease type 2C with scapuloperoneal muscular atrophy overlap syndrome and scapuloperoneal spinal muscular atrophy in one family: a case report and literature review

Background: Charcot-Marie-Tooth disease 2C (CMT2C) and scapuloperoneal spinal muscular atrophy (SPSMA) are different clinical phenotypes of TRPV4 gene mutation. The mutation of p.Arg316Cys has been previously found to cause CMT2C and SPSMA separately. Case presentation Here, we reported a Chinese family harboring the same p.Arg316Cys variant but with overlap syndrome and different clinical manifestations. A 58-year-old man presented with severe scapula muscle atrophy as hanger-like shoulders. Distinct muscle atrophy also presented in his four limbs especially in the lower limbs. Sural nerve biopsy of the father indicated severe loss of myelinated nerve fibers with scattered regenerating clusters and pseudo-onion bulbs. Nerve conduction study indicated axon damage in both motor and sensory nerves. Sensory nerve action potentials could not be evocated in bilateral sural or superficial peroneal nerves. He was diagnosed with Charcot-Marie-Tooth disease type 2C and scapuloperoneal muscular atrophy overlap syndrome. While his 27-year-old son was born with club foot and clinodactyly. Electromyogram examination indicated chronic neurogenic changes and anterior horn cells involvement. He complained of no obvious weakness or sensory symptoms currently. Early SPSMA could be considered for him. Conclusion A literature review of the clinical characteristics in CMT2C and SPSMA patients with TRPV4 gene mutation suggested that our case was distinct for his overlap syndrome. Altogether, this case broadened the phenotype spectrum and supplied the nerve biopsy pathological characters of TRPV4 gene mutation related neuropathy.