Multimodal Evaluation of Bethlem Myopathy with the c.788G > A Variant in the COL6A1 Gene: a case report with genetic, ultrasonographic, and structural-functional discordance correlations.

Introduction: Bethlem myopathy (BM) is a collagen-VI-related myopathy caused by mutations in the COL6A1, COL6A2, and COL6A3 genes. It is characterized by proximal muscle weakness, distal joint laxity, and contractures, with symptoms appearing during childhood and progressing slowly. Muscle ultrasound, using tools like the Heckmatt scale, complements genetic analysis and provides noninvasive insights into muscle pathology, particularly in atypical presentations.

Case report: An 8-year-old male presented with muscle weakness since birth, delayed motor milestones, toe walking, and frequent falls. Family history revealed maternal-line neuromuscular disorders. Clinical examination showed hyporeflexia, thoracic hypotrophy, and decreased proximal muscle strength, alongside joint hypermobility and keratosis pilaris. Electromyography indicated a myopathic pattern in proximal upper limb muscles. Genetic analysis confirmed a pathogenic COL6A1 variant (c.788G > A, p.Gly263Asp). Ultrasound findings revealed advanced structural compromise with Heckmatt grade IV echogenicity in the deltoid, iliopsoas, and rectus femoris, indicating fatty infiltration and fibrosis. Functional tests, including Motor Function Measurement (MFM), showed adequate performance despite significant structural abnormalities.

Discussion: This case illustrates the diagnostic challenges of BM, characterized by phenotypic variability and the complexity of correlating structural and functional findings. Muscle ultrasound findings demonstrated advanced echogenic changes, but functional performance remained preserved, highlighting a mismatch between structural changes and functional outcomes.

Conclusion: This case highlights the diagnostic challenges of BM, where a patient with a COL6A1 gene mutation exhibited significant muscle abnormalities on ultrasound but maintained relatively preserved motor function according to the MFM scale. This discrepancy emphasizes the limitations of functional assessments like MFM in capturing the extent of muscle weakness. Ultrasound and dynamometry provided a more comprehensive evaluation, underscoring the importance of integrating structural and functional assessments for accurate diagnosis and management. This case stresses the need for an individualized approach in managing BM, considering both genetic and clinical findings.