Clinical and therapeutic impact of whole-exome sequencing in inherited neuromuscular disorders: first autonomous cohort from Algeria

Inherited neuromuscular disorders are characterised by marked clinical and genetic heterogeneity and remain highly exposed to prolonged diagnostic delay, with direct consequences for prognosis, therapeutic timing, surveillance, and family counselling. Whole-exome sequencing (WES) has substantially reshaped the diagnostic trajectory of these conditions, particularly in healthcare systems where access to genomic diagnostics remains limited and where delayed diagnosis may result in missed treatment opportunities. We report four clinically distinct inherited neuromuscular cases investigated through a fully autonomous, in-country WES workflow implemented in Algeria. These cases encompassed Duchenne muscular dystrophy ( DMD ), limb-girdle muscular dystrophy R5 ( SGCG ), infantile-onset Pompe disease ( GAA ) superimposed on an unresolved dysmorphic syndrome, and a dynein-related neuromuscular disorder ( DYNC1H1 ). Diagnostic delay ranged from approximately two to six years, during which multiple non-contributive investigations had been performed, including electromyography, muscle imaging, MLPA, and prolonged clinical follow-up. WES established a definitive molecular diagnosis in all four cases and led to major clinical consequences. These included nosological reclassification, genotype-guided phenotypic reassessment, avoidance of invasive or redundant investigations, implementation of targeted surveillance strategies, cascade familial testing, and direct therapeutic impact. Most notably, WES enabled the diagnosis of infantile-onset Pompe disease in a phenotypically masked syndromic context, allowing timely initiation of enzyme replacement therapy. Beyond diagnostic performance, this study illustrates the multidimensional clinical and therapeutic utility of WES in inherited neuromuscular disorders and demonstrates the feasibility of a fully localised genomic workflow in a middle-income setting. These findings support the early integration of WES into neuromuscular diagnostic pathways, particularly when delayed molecular confirmation may compromise therapeutic opportunities.