TRPV4 neuromuscular disease registry highlights bulbar, skeletal and proximal limb manifestations - Report - MDSpire

TRPV4 neuromuscular disease registry highlights bulbar, skeletal and proximal limb manifestations

  • By

  • Gage P Kosmanopoulos

  • Jack K Donohue

  • Maya Hoke

  • Simone Thomas

  • Margo A Peyton

  • Linh Vo

  • Thomas O Crawford

  • Reza Sadjadi

  • David N Herrmann

  • Sabrina W Yum

  • Mary M Reilly

  • Steven S Scherer

  • Richard S Finkel

  • Richard A Lewis

  • Davide Pareyson

  • Chiara Pisciotta

  • David Walk

  • Michael E Shy

  • Charlotte J Sumner

  • Inherited Neuropathies Consortium - Rare Disease Clinical Research Network

  • Eleonora Cavalca

  • Luca Crivellari

  • John Day

  • Matilde Laura

  • Stefania Magri

  • Isabella Moroni

  • Bipasha Mukherjee-Clavin

  • Emanuela Pagliano

  • Alex Rossor

  • Paola Saveri

  • Giulia Schirinzi

  • Mariola Skorupinska

  • Janet Sowden

  • Franco Taroni

  • Elizabeth Wood

  • Brett A McCray

  • June 25, 2024

  • 0 min

Share

Clinical Report: TRPV4 Neuromuscular Disorders Show Bulbar, Limb, and Skeletal Symptoms

Overview

Dominant TRPV4 mutations cause neuromuscular diseases characterized by motor-predominant dysfunction, vocal fold weakness, respiratory issues, and skeletal abnormalities. A registry of 68 patients revealed distinct clinical features including proximal limb weakness and a bimodal age of onset, with infantile onset cases showing less sensory involvement and slower progression.

Background

Charcot-Marie-Tooth disease (CMT) and spinal muscular atrophy (SMA) are hereditary neuromuscular disorders caused by mutations in various genes, including TRPV4. TRPV4 mutations lead to gain-of-function ion channel activity causing motor neuropathy with variable sensory involvement. These disorders manifest as CMT type 2C, scapuloperoneal SMA, and congenital distal SMA, with overlapping phenotypes complicating diagnosis and treatment. Understanding the clinical spectrum and natural history of TRPV4-related disease is critical for designing effective clinical trials and therapeutic strategies.

Data Highlights

FeaturePrevalence (%)
Vocal fold weakness55
Shortness of breath55
Ventilatory support required11
Scoliosis64
Arthrogryposis33
Foot deformitiesNot specified

Key Findings

  • TRPV4-related neuromuscular disease shows a bimodal age of onset, with a major peak in the first two years of life.
  • Patients exhibit more proximal arm and leg muscle involvement and greater ambulatory difficulties compared to CMT1A patients.
  • Motor dysfunction predominates over sensory symptoms, though sensory deficits are often clinically detectable.
  • Over half of patients experience vocal fold weakness and respiratory symptoms; a subset requires ventilatory support.
  • Skeletal abnormalities such as scoliosis and arthrogryposis are common among affected individuals.
  • Infantile-onset patients demonstrate less sensory involvement and slower disease progression based on CMT Examination Scores.

Clinical Implications

Clinicians should recognize the distinctive motor-predominant phenotype of TRPV4-related neuromuscular disease, including proximal limb weakness and bulbar involvement. Respiratory function and vocal fold status require routine monitoring due to frequent impairment. Outcome measures for clinical trials should incorporate assessments of non-length dependent motor dysfunction, respiratory capacity, and vocal fold function to capture disease impact accurately.

Conclusion

This registry study delineates the unique clinical spectrum of TRPV4-related neuromuscular disorders, highlighting the need for tailored clinical assessments and outcome measures. These insights will facilitate rational clinical trial design and therapeutic development targeting TRPV4 channel dysfunction.

References

  1. Original Article -- Registry of TRPV4-Related Neuromuscular Disorders Reveals Bulbar, Skeletal, and Proximal Limb Symptoms

Original Source(s)

TRPV4 neuromuscular disease registry highlights bulbar, skeletal and proximal limb manifestations

  • by Gage P Kosmanopoulos, Jack K Donohue, Maya Hoke, Simone Thomas, Margo A Peyton, Linh Vo, Thomas O Crawford, Reza Sadjadi, David N Herrmann, Sabrina W Yum, Mary M Reilly, Steven S Scherer, Richard S Finkel, Richard A Lewis, Davide Pareyson, Chiara Pisciotta, David Walk, Michael E Shy, Charlotte J Sumner, Inherited Neuropathies Consortium - Rare Disease Clinical Research Network, Eleonora Cavalca, Luca Crivellari, John Day, Matilde Laura, Stefania Magri, Isabella Moroni, Bipasha Mukherjee-Clavin, Emanuela Pagliano, Alex Rossor, Paola Saveri, Giulia Schirinzi, Mariola Skorupinska, Janet Sowden, Franco Taroni, Elizabeth Wood, Brett A McCray

  • June 25, 2024

Related Content

Ultrasound Models Estimate Whole-Body Muscle Mass

New equations incorporating cross-sectional area improve estimation accuracy.

Comparison of Low-Dose and Standard-Dose Intravenous Immunoglobulin for Treating Generalized Myasthenia Gravis: A Prospective Cohort Study at a Single Center

Medical Oddities: Tattoos and Teeth Share Work Struggles

From unexpected workplace parallels to kitchen-counter experiments and a few clinical twists, this set of stories covered more ground than your average shift.