From the Guidelines
Testing for Bethlem myopathy later in life should primarily involve genetic testing for mutations in the COL6A1, COL6A2, and COL6A3 genes, as this approach provides the most definitive diagnosis. This is because genetic testing can identify specific mutations that encode collagen VI proteins, which are associated with Bethlem myopathy. A blood sample is collected and sent to a specialized laboratory where DNA is extracted and analyzed for these specific mutations 1.
Clinical Evaluation and Additional Tests
Clinical evaluation by a neurologist or neuromuscular specialist is also essential, focusing on characteristic symptoms like:
- Joint contractures (especially in fingers, elbows, and ankles)
- Skin abnormalities
- Mild to moderate muscle weakness with a slow progression Muscle biopsy may sometimes be performed to examine muscle tissue structure and collagen VI expression, though this is becoming less common with advances in genetic testing 1. Muscle imaging techniques like MRI can help identify patterns of muscle involvement characteristic of Bethlem myopathy.
Importance of Early Diagnosis
Early diagnosis is important for appropriate management of contractures and muscle weakness, even when symptoms appear later in life. The testing process should be coordinated through a neuromuscular specialist or genetic counselor who can interpret results and provide guidance on disease management. This comprehensive approach ensures that patients receive timely and effective care, improving their quality of life and reducing morbidity and mortality associated with Bethlem myopathy.
From the Research
Testing for Bethlem Myopathy Later in Life
To test for Bethlem myopathy later in life, the following methods can be used:
- Muscle magnetic resonance imaging (MRI) to establish the pattern and degree of muscle involvement 2
- Genetic testing through next-generation sequencing of custom amplicon-based targeted genes panel of myopathies to identify mutations in the COL6A1, COL6A2, and COL6A3 genes 3, 4
- Whole exome sequencing (WES) in combination with neuromuscular diseases-associated genes-filtering to detect possible causative mutations 4
- Clinical evaluation, including assessment of muscle weakness, joint contractures, and other musculoskeletal abnormalities 5
- Laboratory tests, such as creatine kinase (CK) levels, although CK levels may not correlate with disease severity 3
Key Findings
- Muscle MRI findings in Bethlem myopathy show a specific pattern of muscle involvement, with variable severity in parallel with the severity of motor function impairment 2
- Genetic mutations in the COL6A1, COL6A2, and COL6A3 genes are associated with Bethlem myopathy, with some mutations predicting a more severe clinical evolution 3, 4, 6
- The clinical manifestations of Bethlem myopathy are highly variable, and no phenotype-genotype correlation has been described 3
- Long-term follow-up of patients with Bethlem myopathy identifies important phenotypic variability, with worsening of functional disability typically occurring after the age of 40 6