G.P.265: Nebulin-related nemaline myopathy: Clinical and histopathological spectrum in Argentinean patients

Abstract

Nebulin (NEB) is a sarcomeric structural protein. Mutations in NEB genes particularly cause autosomal recessive nemaline myopathy (NM) and core-rod myopathy. Clinical presentations range from a severe neonatal form to a mild adult-onset form as part of the different diagnosis of distal myopathy. We describe the clinical, histopathological, and molecular findings of three patients with different phenotypes of NEB gene mutations. Case 1: A 5-year-old boy with distal finger retractions, hypotonia, and motor development delay since birth with mainly distal general weakness and hyperlaxity. At age 1 he developed progressive respiratory difficulties needing ongoing invasive ventilation by tracheostomy. He was never able to walk. Spine surgery was performed at 4years. Cognitive development was normal. Quadriceps muscle biopsy showed NM consisting of rod structures, type 1 predominance and atrophy. Exome sequencing showed mutations in exon 139 and 172. Case 2: A 2.5-year-old girl presenting with motor developmental delay, hypomimia, and hypotonia since birth. At 18months of age she walked independently and steppage gait was noticed. She is still improving. Deltoid biopsy showed NM consisting of rod structures and type 1 predominance. Exome sequencing showed mutations in intron 12 and exon 150. Case 3: A 22-year-old girl had frequent falls since she started to walk at 1year, linked to distal hyperlaxity, as well as distal weakness, arreflexia, and steppagge gait. Slow symptom progression was seen. EMG ruled out neuropathic disease and muscle biopsy showed rod and core structures with type 1 predominance. Exome sequencing showed mutations in exon 129 and exon 74 to exon144. Conclusion: NEB-related NM has a broad clinical spectrum particularly including congenital and distal myopathy forms that may mimic a neurogenic process. Our three patients presented with predominantly distal weakness and muscle biopsies showed rod or core-rod myopathies.