The goal of this research is to document the symptoms and disease progression in patients with TRPV4 neuromuscular disease. Additionally, the study will evaluate different ways of measuring disease symptoms in order to measure disease severity and track how symptoms change over time.

Mutations in TRPV4 cause a range of inherited neuromuscular diseases which share features of progressive weakness of the arms and legs, variably sensory difficulties, and frequent weakness of vocal cords and breathing muscles. TRPV4 is an ion channel that allows calcium ions to flow into cells. Work in animal models of this condition has shown that disease mutations cause TRPV4 to be overactive, and drugs that block the channel are effective as treatments in these models. This suggests that TRPV4 blocking drugs could potentially be used as a treatment for patients with TRPV4 neuromuscular disease. To help prepare for possible future clinical trials, this study will seek to 1) define the natural history of TRPV4 neuromuscular disease and 2) identify relevant outcome measures and markers of disease biomarkers that can be used in future clinical trials.

The eligible conditions include all forms of neuromuscular disease caused by mutations in TRPV4, which can be referred to as CMT2C, scapuloperoneal spinal muscular atrophy (SPSMA), or congenital distal spinal muscular atrophy (CDSMA). If the patient has a variant of unknown significance in the TRPV4 gene, their clinical phenotype must be consistent with the spectrum of TRPV4 neuromuscular diseases.

Children (aged 3 and older) and adults with a confirmed genetic mutation in the TRPV4 gene and clinical symptoms consistent with TRPV4 neuromuscular disease are encouraged to participate in this study.As a participant in the study, you would be asked to visit Johns Hopkins on an annual basis for 6 years. The study testing is scheduled to occur over two days for each visit. Participants will be reimbursed for travel expenses and hotel accommodations, and all tests will be performed free of charge. Planned testing includes thorough neurological exams, nerve conduction studies, standardized questionnaires, brain MRIs, skeletal X-rays and bone density scans (DEXA), vocal cord and voice assessments, retinal (eye) scans, and a series of tests to evaluate the ability to perform tasks of daily living such as getting up from a chair or walking for six minutes. The investigators will also collect blood samples from each participant to be used for laboratory research.

Enrollment for this study is expected to start at Johns Hopkins between October and December 2023.

If you think you or a family member might be eligible and interested in taking part in this research, or would like any further information, please contact the study team directly with the subject line ‘CMTA Referral for TRPV4 Research’. Email: or by Phone: 410-502-2705.