P.280 - The natural history of nemaline myopathy

Abstract

Nemaline myopathy (NM) is characterized by weakness, hypotonia and respiratory distress due to mutations in at least 12 genes with various inheritance patterns. Currently, no treatment exists. This study represents the first longitudinal examination of NM patients, providing a more accurate estimate of the rate of change and a more precise documentation of the clinical phenotype. Participants were evaluated at family conferences in 2009 and 2016. Physical examinations, pulmonary function testing (PFT) and motor function assessment (MFM20) were performed along with collection of medical history. 58 patients were enrolled with 17 participating at both time points. Ages ranged from 1–37 years (73% under age 18). Genotypes included 24% ACTA1, 29% NEB, 3% TPM2 and 43% unknown. The majority of participants were ambulant (67%) and required respiratory support (60%). Motor function testing using MFM20 showed a clinically meaningful decrease of total scores in 54% between time points, while 31% remained stable. Participants demonstrated greatest difficulty in domain 1, representing standing and transfers. Of those requiring respiratory support, 52% required invasive ventilation. PFT revealed significant respiratory involvement with the majority of patients below the clinical cutoffs for MIPS (90%), peak cough flow (53%) and FVC (74%). Longitudinal analysis of PFT's (n = 4) showed stable peak cough flow and FVC with increasing MIPS. Many of participants did not have a severe phenotype based on the requirement of technologies (wheelchair, trach/vent, G/GJ tube) as 41% did not require any support, while only 15% required all three. NM represents a wide clinical spectrum, with the majority of patients on the milder end compared to other congenital myopathies. Motor function appears to decrease over time, while respiratory status remains relatively stable. MFM20 and PFT's look promising for use as outcome measures in future clinical trials.