Bethlem myopathy: A novel homozygous variant of c.385C>T (p.Arg129Cys) in the COL6A2 gene.

Abstract

This case highlights the challenges in diagnosing Bethlem myopathy, the need for a high index of suspicion, and the importance of recognizing the diverse clinical presentations of this rare condition. Enhanced understanding can aid in early diagnosis and tailored management. Bethlem myopathy (BM), a rare collagen VI-related myopathy, is characterized by progressive muscle weakness and contractures, typically affecting the proximal muscles and joints. This case report presents a 15-year-old girl from Tehran, Iran, with a 5-year history of severe limb pain and progressive weakness. Born to consanguineous parents, the patient displayed delayed walking milestones and significant hypotonia, leading to a waddling gait and lumbar hyperlordosis. Neurological examination revealed marked proximal lower limb weakness, a positive Gowers' sign, and absent myotatic reflexes. Elevated creatine phosphokinase (CPK) levels and electromyography (EMG) results indicated myopathy, while nerve conduction studies showed no neuropathy. Genetic testing revealed a novel homozygous variant of c.385C>T (p.Arg129Cys) in the COL6A2 gene, classified as a variant of uncertain significance (VUS) per American College of Medical Genetics and Genomics (ACMG) guidelines due to its rarity and specific phenotype association. Differential diagnosis is essential to distinguish it from other neuromuscular conditions. Management primarily focuses on symptom relief and enhancing patients' quality of life. This case highlights the challenges in diagnosing BM, the need for a high index of suspicion, and the importance of recognizing the diverse clinical presentations of this rare condition. Enhanced understanding can aid in early diagnosis and tailored management.