X-linked Emery-Dreifuss muscular dystrophy: a multicenter, Italian, cohort study

Area of Science:

• Neurology
• Genetics
• Cardiology

Background:

• X-linked Emery-Dreifuss muscular dystrophy (EDMD1) is a rare, early-onset myopathy affecting approximately 1 in 400,000 individuals.
• Characterized by humeroperoneal weakness, contractures, and cardiac involvement, its natural history is poorly understood due to limited patient data in previous studies.
• This study aimed to elucidate the clinical and molecular characteristics of EDMD1 in a substantial Italian patient cohort.

Purpose of the Study:

• To investigate the clinical and molecular features of X-linked Emery-Dreifuss muscular dystrophy (EDMD1).
• To analyze the natural history of EDMD1 in a large Italian cohort.
• To identify novel mutations associated with EDMD1.

Main Methods:

• Retrospective data collection from 38 genetically confirmed EDMD1 males and 10 female carriers across 14 Italian centers.
• Inclusion criteria required detectable muscle weakness or contractures on neurological examination.
• Data analysis focused on clinical presentation, age of onset, cardiac involvement, motor performance, and genetic mutations.

Main Results:

• The mean age of disease onset was 12.0 ± 3.4 years, with 84.2% presenting with muscle weakness/contractures and 15.8% with cardiac symptoms.
• Cardiac involvement was observed in 76.3% of patients, with a mean onset age of 24.2 ± 13.1 years; onset age differed significantly between cardiac and muscular presentations (p=0.0011).
• Patients with muscular onset showed poorer motor performance (p=0.0163), and 10 novel EMD mutations were identified.

Conclusions:

• The natural history of EDMD1 is predominantly characterized by cardiac involvement.
• Skeletal muscle weakness in EDMD1 progresses gradually over time.
• This study provides valuable insights into EDMD1's clinical spectrum and genetic landscape.