ベスレムミオパチー

Bethlem myopathy is a rare collagen VI-related muscle disorder characterised by slowly progressive proximal weakness and joint contractures. Walking is usually preserved into adulthood and respiratory involvement is relatively mild. A 53-year-old woman had longstanding proximal limb weakness, early contractures and respiratory insufficiency. Despite an apparent clinical improvement on follow-up, initially attributed to immunotherapy, genetic testing ultimately identified a pathogenic COL6A1 mutation. This case highlights diagnostic challenges in late-presenting myopathies and emphasises the importance of genetic testing in atypical cases.

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.

AIM: Collagen VI has recently been strongly linked to poor outcomes in heart failure through increased endotrophin, a collagen VI-derived signaling molecule linked to fibrotic remodeling in cardiovascular disease. The mutation of collagen VI can result in Ullrich congenital muscular dystrophy and Bethlem myopathy, pointing to a critical function in muscle physiology. However, the functional role of collagen VI in the heart is poorly understood. In human heart failure with reduced ejection fraction, collagen VI is increased within the remodeled T-tubules, suggesting a possible role in tubular structure and Ca2+ dynamics. METHODS: To investigate this hypothesis, a global knockout of the collagen VI alpha 1 gene (Col6a1-/-) was generated in the rat. RESULTS: T-tubule structure and ryanodine receptor cluster organization were unchanged, but echocardiography demonstrated reduced systolic function. Consistent with this, isolated trabeculae from Col6a1-/- hearts generated significantly less peak stress, confirming impaired contractile force at the tissue level. Paradoxically, isolated cardiomyocytes from the Col6a1-/- rat had increased Ca2+ transient amplitude and increased sarcoplasmic reticulum Ca2+ load that would be expected to increase force. β-adrenergic stimulation further increased Ca2+ transient amplitude and was associated with diastolic Ca2+ release events in Col6a1-/- cardiomyocytes. Furthermore, β-adrenergic stimulation of Col6a1-/- trabeculae exhibited spontaneous contractions, indicating an increased susceptibility to arrhythmic activity. CONCLUSION: Together, these results indicate collagen VI has a role in both force transduction and Ca2+ cycling in the heart.

We describe a young man with persistent hyperCKemia and MRI findings initially suggestive of inflammatory myopathy, in whom genetic testing confirmed Bethlem myopathy. This case illustrates how collagen VI-related myopathies can mimic idiopathic inflammatory myopathies (IIM), underlining the need for integrated clinical, imaging, biopsy, and genetic data to ensure diagnostic accuracy and avoid unnecessary immunosuppression.

OBJECTIVES: Collagen 6-related Bethlem myopathy and LDLR-related familial hypercholesterolemia are presumed to be quite rare in the general population. CASE REPORT: Here, we present the clinical findings from a 65-year-old man with comorbid Bethlem myopathy and familial hypercholesterolemia to highlight some important molecular diagnostic considerations and clinical management implications.