Introduction

Tissue biopsy has long been gold standard for diagnosis of neuromuscular disorders(NMDs). Next generation sequencing(NGS) is rapidly gaining importance as non-invasive diagnostic tool for suspected genetic NMDs.

Objectives

To evaluate diagnostic yield of NGS in children with suspected genetic NMDs.

Methods

After detailed clinical, neurophysiological and biochemical assessment, confirmation of specific NMDs was done by NGS in 76/150 children over last 4 years. Genetic variants identified were correlated with parental genetics and patient history to evaluate clinical significance.

Results

NGS was done only in 76/150 children with suspected NMDs (muscle-117; nerve-28; Neuromuscular junction(NMJs)-5 due to financial constraints. 50/76, 21/76 and 5/76 belonged to muscle, nerve and NMJ disorders respectively.

45/117 children with muscle disorders suspected to have DMD were confirmed by genetic testing- 38 were exon deletions(MLPA) and 7 were point mutations(NGS). NGS revealed positive results in 44/50(88%) suspected muscle disorders. 12/44 with COL6A related myopathy, 7/44 with DMD and 8/44 with CMD were common genetic variants.

21/28(75%) with nerve disorders gave positive yield. CMT neuropathy with varying genotypes was the most common aetiology observed.

3/5(60%) with suspected congenital NMJ disorders was positive for COLQ, DOK7 and CHRNE genes respectively.

Overall NGS diagnostic yield was 81.9% with 88%, 75% and 60% in muscle, nerve and NMJ disorders respectively.

Conclusion

• NGS, a non invasive, confirmatory diagnostic tool, has a high positive yield (81.9%) in NMD
• In developing countries, cost constraints limit its uniform use.
• Early diagnosis would help with early intervention, prognostication and research-based treatment options for affected patients.