P.235Clinico-pathological characterisation of CACNA1S related congenital myopathy in children

Abstract

Mutations in the CACNA1S gene were recently identified as a new cause of congenital myopathy (CM). To date only a few cases have been described, with limited phenotypic data. We report the clinical, pathological and radiological phenotype in five children with genetically confirmed CACNA1S-CM. →Patients were referred to our national highly specialised service for CM at The Dubowitz Neuromuscular Centre, UK. We conducted retrospective case note analysis. Two patients had recessive inheritance and three autosomal dominant. →Four of five patients (age range 7-18 years) had severe neonatal presentation with foetal akinesia, weakness, hypotonia, contractures, feeding difficulties and respiratory compromise. The 5th patient presented with motor delay in infancy. All five patients had proximal predominant, bulbar and facial weakness but showed spontaneous improvement over time. Ophthalmoplegia was noted in three. Two patients remain non-ambulant. Two developed scoliosis. Two are on nocturnal non-invasive ventilation initiated at age of 5 months and 7 years. All apart from one required nasogastric/gastrostomy feeding up until 2-5 years of age, but all were able to feed orally from age 5 years. One patient had clear history of periodic weakness well responding to Acetazolamide. Two children reported fatigue and limited endurance but no abnormalities of neuromuscular transmission were detected. All muscle biopsies showed fibre size variation and marked slow fibre predominance. Additional findings included mild central nucleation, few central cores and focally accentuated pseudo-dystrophic changes. Three out of the five patients had abnormal lower limb muscle MRI but with no specific muscle pattern. →CACNA1S related myopathy is a recently described form of congenital myopathy and should be considered in cases of undiagnosed dominant and recessive congenital myopathies with phenotypical features presented above.