Next-generation sequencing for pediatric-onset neuromuscular disorders unresolved by conventional diagnostic methods

Neuromuscular disorders (NMDs), rare diseases affecting the peripheral nervous system, often cause progressive weakness and systemic complications. Despite advances in genetic diagnostics, data from Southeast Asia remain limited. Ancestral variation may influence mutation spectra, revealing novel alleles and phenotypic diversity.

We evaluated the diagnostic yield and clinical impact of targeted gene panel testing and exome sequencing in pediatric-onset NMDs at Siriraj Hospital, Thailand (2020‒2024). Patients with suspected genetic NMDs and negative single-gene tests underwent gene panel testing or exome sequencing. Genetic findings were classified as positive, probable, possible, or negative.

Among 135 patients, the overall diagnostic yield was 69.6% (94/135). Subgroup yields were 70.7% for inherited myopathies (53/75), 63.3% for inherited neuropathies (31/49), 90.0% for congenital myasthenic syndromes (9/10), and 100% for motor neuron diseases (1/1). Excluding patients with Duchenne muscular dystrophy, the diagnostic yield of inherited myopathies was 63.2% (36/57). Genetic diagnoses influenced clinical care in 87.2% of cases, prompting revised diagnoses, personalized treatments, enhanced surveillance, informed family planning, and accurate prognostication.

NGS substantially enhances diagnostic accuracy and clinical management for pediatric NMDs. These findings support incorporating NGS into diagnostic workflows for suspected genetic NMDs, thereby optimizing patient care and advancing genetic insights.

Gene panel testing and exome sequencing demonstrate an approximately 70% diagnostic yield for pediatric neuromuscular disorders, exceeding yields reported in many other hereditary diseases. Genetic findings underscore potential differences in mutation spectra among Southeast Asian populations, which remain under-investigated relative to Western cohorts. Clinical implementation of next-generation sequencing confers substantial benefits, including more accurate diagnoses, personalized management, and informed family planning, ultimately improving care for pediatric neuromuscular disorders.