P.166Retrospective longitudinal study of patients with NEB-related nemaline myopathy in the United Kingdom

Abstract

Recessive mutations in the NEB gene encoding nebulin are the most common known cause of nemaline myopathy (NEB-NM). Natural history studies on NEB-NM are limited and mostly focused on cross sectional data. We present a retrospective longitudinal study of 24 NEB-NM patients seen at the Dubowitz Neuromuscular Centre and the Evelina Children's Hospital, London. Age range was 2.93-27 years (median 17.34 yrs), follow up range 1.75-12.25 years (median 4.75 yrs), with a median of 5 yearly follow-up/patients (2-13 yrs). All patients were homozygous or compound heterozygous for 2 NEB variants. Altogether, 26 variants were identified, 4 missense, 17 frameshift, 5 splice site. Longitudinal motor function scores on the Hammersmith Functional Motor Scale were available for 13 patients, with a median of 4 assessments/child. Two patients with severe NEB-NM never sat independently, 2 with the typical form lost ambulation at 6 and 12 years, respectively. All other patients were ambulant at last follow-up. 17 patients (70%) developed scoliosis and/or kyphosis, 7 had spinal surgery at a median age of 15 years (11-16.42 yrs). Forced vital capacity % trends were available for 12 patients, with a median of 4 yearly measurements/child. 9/24 (37.5%) patients required nocturnal non-invasive ventilation at a median age of 8 years (2-18.5 yrs). Two patients with severe NEB-NM required tracheostomy before age 6 months and one, with typical form, after spinal surgery at 11 years. One patient died aged 19 years due to respiratory complications. Weight trends were available for 16 patients, with a median of 4.5 measurements/child. Gastrostomy was needed in 11/24 (46%) at a median age of 4 years (0-15.75 yrs). Statistical analysis is now in progress to describe trajectories and calculate estimated change/year of motor abilities, FVC and weight. This study expands knowledge on clinical course of NEB-NM and further emphasizes the importance of long-term multidisciplinary assessment and management.