From biopsy to genotype: Clinical and genetic landscape of pediatric congenital myopathies in a single-centre series.

Background

Congenital myopathies are rare inherited neuromuscular disorders with overlapping clinical and histopathological features. Genotype-phenotype correlation is important for prognosis, respiratory surveillance and genetic counselling.

Objectives

To describe the demographic profile, genetic spectrum, genotype-phenotype correlation and outcomes of children with congenital myopathies from a tertiary care centre in South India.

Methods

This retrospective observational study included children younger than 18 years with genetically confirmed congenital myopathy diagnosed over a four-year period. Demographic details, age at symptom onset, clinical phenotype, respiratory involvement, serum creatine kinase levels, biopsy findings, genetic diagnosis, ambulatory status and outcomes were analyzed descriptively.

Results

Twelve children were included, with equal sex distribution. Symptom onset occurred predominantly in infancy or early childhood. RYR1 was the most frequent gene, identified in five children (41.7%), followed by SELENON and collagen VI-related genes. RYR1-related disease showed a variable phenotype, ranging from severe neonatal presentation to milder symptomatic forms with markedly elevated creatine kinase (CK). SELENON-related myopathy was associated with prominent axial weakness and respiratory morbidity. Collagen VI-related disorders showed joint laxity, contractures and retained ambulation, suggesting intermediate to severe phenotype. NEB-related myopathy with typical features was identified in one child. A rare form, CACNA1S myopathy was identified in one child. Respiratory involvement was observed in four children (33.3%). Eleven children survived, and one neonate with RYR1 myopathy died following severe respiratory failure.

Conclusions

This series highlights the shift from biopsy-centred to genotype-centred diagnosis, while supporting the continued role of muscle biopsy in genotype-negative, uncertain or discordant cases.