Adult centronuclear myopathies: A hospital-based study

Area of Science:

• Neurology
• Genetics
• Rare Diseases

Background:

• Centronuclear myopathies (CNM) are inherited neuromuscular disorders.
• Characterized by centrally located nuclei in muscle fibers.
• Key genes include MTM1, DNM2, and BIN1, each associated with different inheritance patterns.

Purpose of the Study:

• To describe the clinical and molecular characteristics of adult CNM patients.
• To identify the genetic causes of CNM in a cohort of adult patients.
• To assess the spectrum of clinical manifestations and associated conditions in adult CNM.

Main Methods:

• Retrospective monocentric study of 14 adult CNM patients (2000-2012).
• Standardized clinical examinations, biological tests, electrophysiology, muscle biopsy, and molecular testing were performed.
• Analysis included patients from families and sporadic cases.

Main Results:

• Seven patients developed CNM before 15, seven after 25; all had mild, slowly progressive distal weakness.
• Commonly observed: cognitive impairment (7), axonal polyneuropathy (6), ophthalmoparesis/ptosis (5).
• DNM2 mutations identified in 8 patients; BIN1 and MTM1 mutations were absent. Six patients lacked molecular diagnosis.

Conclusions:

• Adult CNM presents as a slowly progressive distal myopathy with normal CK levels.
• DNM2 mutations are the primary cause in this adult cohort, including autosomal dominant and sporadic cases.
• The absence of MTM1/BIN1 mutations and the presence of undiagnosed cases suggest undiscovered CNM-causing genes.