Homozygous missense variant in exon 66 of the RYR1 gene causing congenital myopathy 1B

Congenital myopathy 1B is a rare autosomal recessive disorder caused by mutations in the RYR1 gene. The disease has a highly variable phenotype, which can be fatal in the neonatal period. The poor prognosis of this disease makes the prenatal identification of the mutation important, and thus, reporting of all likely pathogenic variants of the RYR1 gene is crucial. Here, we present a new likely pathogenic variant of the RYR1 gene. A late preterm neonate with an antenatal history of polyhydramnios, decreased foetal movements, delivered to consanguineous parents, required resuscitation at birth. Other features noted were high arched palate, pooling of oral secretions, bitemporal hollowing, inverted V-shaped upper lip, paradoxical movement of the bilateral chest wall, undescended testis, absent gag reflex, and generalized hypotonia. Baby remained ventilator dependent and succumbed at 6 weeks of life. Clinical exome was reported as a homozygous missense variant in exon 66 of the RYR1 gene, chromosome 19 that results in the amino acid substitution of proline for leucine at codon 3316. Sanger sequencing was done for both parents, who were reported as heterozygous carriers. This was classified as a variant of uncertain significance due to a dearth of reported literature. Considering the highly correlated phenotype and confirmed heterozygous carrier status in asymptomatic parents, this report could aid in concluding that this mutation is likely pathogenic.