biostudies-literatureKosmanopoulos GPNational Institute of Neurological Disorders and StrokeRare Diseases Clinical Research NetworkInherited Neuropathies ConsortiumOffice of Rare Diseases ResearchNINDS NIH HHSNIHNIH HHSMuscular Dystrophy AssociationNIH National Center for Advancing Translational SciencesINC238-251https://www.ebi.ac.uk/biostudies/studies/S-EPMC12054732biostudies-literatureUnknown148(1)Dominant missense mutations of the calcium-permeable cation channel TRPV4 cause Charcot-Marie-Tooth disease (CMT) type 2C and two forms of distal spinal muscular atrophy. These conditions are collectively referred to as TRPV4-related neuromuscular disease and share features of motor greater than sensory dysfunction and frequent vocal fold weakness. Pathogenic variants lead to gain of ion channel function that can be rescued by TRPV4 antagonists in cellular and animal models. As small molecule TRPV4 antagonists have proven safe in trials for other disease indications, channel inhibition is a promising therapeutic strategy for TRPV4 patients. However, the current knowledge of the clinical features and natural history of TRPV4-related neuromuscular disease is insufficient to enable rational cBrain : a journal of neurologyTRPV4 neuromuscular disease registry highlights bulbar, skeletal and proximal limb manifestations.PMC12054732R01 NS131402U54 NS065712R35 NS122306U54NS065712K08 NS102509629305Herrmann DNMcCray BAHoke MMoroni IShy MEPeyton MAInherited Neuropathies Consortium - Rare Disease Clinical Research NetworkDay JSowden JScherer SSDonohue JKPisciotta CKosmanopoulos GPThomas SCrawford TOLaura MSaveri PLewis RATaroni FPareyson DCavalca EPagliano EFinkel RSVo LSumner CJYum SWWalk DSchirinzi GCrivellari LSkorupinska MWood EReilly MMMagri SRossor ASadjadi RMukherjee-Clavin BfalseTRPV4 neuromuscular disease registry highlights bulbar, skeletal and proximal limb manifestations.Dominant missense mutations of the calcium-permeable cation channel TRPV4 cause Charcot-Marie-Tooth disease (CMT) type 2C and two forms of distal spinal muscular atrophy. These conditions are collectively referred to as TRPV4-related neuromuscular disease and share features of motor greater than sensory dysfunction and frequent vocal fold weakness. Pathogenic variants lead to gain of ion channel function that can be rescued by TRPV4 antagonists in cellular and animal models. As small molecule TRPV4 antagonists have proven safe in trials for other disease indications, channel inhibition is a promising therapeutic strategy for TRPV4 patients. However, the current knowledge of the clinical features and natural history of TRPV4-related neuromuscular disease is insufficient to enable rational c2025-01-01T00:00:00Z2025 Jan2026-06-01T06:30:31.499Z2026-04-08T10:06:43.197ZS-EPMC120547323891702510.1093/brain/awae201