P.350 - Recurrent respiratory failure in a patient with nemaline and myofibrillar myopathy features

Abstract

Mutations in the Nebulin gene (NEB) have been associated with different myopathies including nemaline myopathy, distal myopathy without nemaline rods, distal nemaline myopathy, core-rod myopathy, distal core-rod myopathy, and fetal akinesia. Myofibrillar myopathies are morphologically distinct but genetically heterogeneous muscular dystrophies arising from mutations in Z-disk related proteins. We report a 73-year-old patient who presented with recurrent hypercapnic respiratory failure requiring intubation and mechanical ventilation. She was mildly weak her entire life, and developed progressive dysarthria, dysphagia, and increased weakness with a 20 kg weight loss over 18 months. She also has a history of alcohol abuse. A fraternal twin is similarly affected. The muscle biopsy revealed large nemaline rods as well as hyaline and amorphous structures displaying ectopic expression of multiple proteins. Molecular genetic analysis showed a homozygous splice site mutation in the NEB gene but no mutation in genes known to cause myofibrillar myopathy. We conclude that mutations in Nebulin can present in adult life, and may result in respiratory failure.