Authors : Adedeji Okikiade; Alisha Metha; Richard Adetoye; Stephen Adetoye; A. Chidimma Diala; Tebong Aboh; Anugwa Oluchi

Volume/Issue : Volume 11 - 2026, Issue 4 - April

Google Scholar : https://tinyurl.com/y5ddnsed

Scribd : https://tinyurl.com/bdcnezxp

DOI : https://doi.org/10.38124/ijisrt/26apr353

Note : A published paper may take 4-5 working days from the publication date to appear in PlumX Metrics, Semantic Scholar, and ResearchGate.

Abstract : Collagen VI–related myopathies (COL6-RM) encompass a broad clinical spectrum of inherited neuromuscular disorders ranging from severe Ullrich congenital muscular dystrophy to milder Bethlem myopathy, caused by pathogenic variants in COL6A1, COL6A2, and COL6A3. The pathogenic disruptions in collagen VI compromise extracellular matrix stability, impair autophagic flux, promote mitochondrial permeability transition, and alter fibroblast–myofiber signaling. These disorders are characterized by proximal muscle weakness, joint contractures, distal hyperlaxity, and respiratory compromise. Advances in basic science have revealed that collagen VI deficiency disrupts extracellular matrix (ECM) integrity, impairs autophagy, induces mitochondrial dysfunction, and alters the myomatrix microenvironment, collectively driving progressive muscle degeneration. Diagnosis relies on a multimodal approach that integrates clinical assessment with muscle MRI, histopathology, and next-generation sequencing. Management remains largely supportive; however, emerging strategies, including autophagy enhancers, mitochondrial permeability transition pore (mPTP) inhibitors, extracellular matrix–targeting agents, and genebased therapies show promise for disease modification. Advances in molecular biology have reshaped the understanding of COL6-RM and opened new avenues for targeted treatment. Robust natural history studies and biomarker development are needed to accelerate translational progress. The objective is to synthesize current evidence regarding pathogenesis, clinical presentation, diagnostic modalities, and evolving therapeutic approaches in COL6-RM. This review integrates and synthesizes findings from molecular pathogenesis, diagnostic tools, clinical spectrum, imaging studies, and evolving management while highlighting future therapeutic directions with emphasis on recent mechanisms involving extracellular matrix dysfunction, autophagy impairment, mitochondrial dysregulation, and myomatrix remodeling.

Keywords : Collagen VI, Myopathy, Extracellular Matrix, Autophagy, Mitochondrial Dysfunction, Ullrich Congenital Muscular Dystrophy, Bethlem Myopathy

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