Selenoprotein N‐related myopathy: a retrospective natural history study to guide clinical trials

Abstract Objective To describe clinical features and disease progression of Selenoprotein N‐related myopathy in a large multicenter cohort of patients. Methods Cross‐sectional multicenter data analysis of 60 patients (53 families) with Selenoprotein N‐related myopathy and single‐center retrospective longitudinal analysis of 25 patients (21 families) over a median period of 5.3 years. Results The majority of patients (46/60, 77%) presented before age 2 years with hypotonia, poor head/neck control, and developmental delay. At last assessment (median age 14 years; range 2.5 to 36 years), 10/60 patients had minimal or no ambulation. Ventilatory support was initiated in 50/60 patients at a mean Forced Vital Capacity (FVC) of 38% and at a median age of 13 years. Forty‐five/60 patients developed scoliosis (at median age 12.1 years) and 18 had scoliosis surgery at a median age of 13.6 years. Five children needed nasogastric feeds and/or gastrostomy. Longitudinal data analysis on 25 patients showed progressive decline of Hammersmith functional motor scores (estimated annual change −0.55 point), time to walk 10 meter, time standing from sitting, and from lying. Sixteen patients had weights