Diagnostic Precision in Pediatric Neuromuscular Disorders: A Case Study of Bethlem Myopathy Mimicking Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is the most prevalent and severe form of childhood muscular dystrophy, typically diagnosed in male children who present with progressive proximal muscle weakness, elevated serum creatine kinase (CK), and delayed motor milestones. Phenotypic overlaps with rarer congenital myopathies, however, can complicate early diagnosis. This report describes a four-year-old male who exhibited classic DMD features, including difficulty rising from the floor (Gowers' sign), calf pseudohypertrophy, generalized hypotonia, and a CK level of 1,200 IU/L. Initial multiplex ligation-dependent probe amplification (MLPA) testing for DMD gene deletions and duplications was negative. Whole exome sequencing (WES) subsequently identified a heterozygous pathogenic splice-site variant (c.1056+1G>A) in the COL6A1 gene, confirming a diagnosis of Bethlem myopathy type 1, an autosomal dominant collagen VI-related disorder. The patient was enrolled in a multidisciplinary care program including physical therapy focused on preserving joint mobility and muscle strength, as well as nutritional support to address failure to thrive. This case illustrates the diagnostic challenges posed by phenotypic similarities between dystrophinopathies and collagen myopathies and emphasizes the essential role of WES when first-line genetic testing is inconclusive. Accurate molecular diagnosis informs prognosis, multidisciplinary management, and genetic counseling, thereby enhancing patient care.