Illness-associated muscle weakness in dystroglycanopathies.

Abstract

To describe the phenomenon of acute illness-associated weakness (AIAW) in patients with dystroglycanopathy (DG), determine the frequency of this phenomenon in DGs, and compare it to the frequency in Duchenne-Becker muscular dystrophy (DBMD). Patients enrolled in a DG natural history study provided medical history, including major illnesses or hospitalizations, at enrollment and annually. We noted a recurring syndrome of profound transient weakness in the setting of febrile illness. To determine the frequency of this phenomenon in the DG cohort and compare it to a cohort with another membrane-related muscular dystrophy, DBMD, we surveyed patients (e-survey tool), collecting demographics and information about episodes of sudden progression of weakness and events surrounding the episodes. Surveys were completed by 52 (56.6%) patients with DG and 51 (27.3%) patients with DBMD. AIAW was reported in 12 (23%) patients with DG and 2 (4%) patients with DBMD (odds ratio 7.35; 95% confidence interval 1.55, 34.77; <i>p</i> = 0.005). Altogether (history or survey), 21 patients with DG, with mutations in <i>FKRP</i>, <i>FKTN</i>, <i>POMT1</i>, <i>POMT2</i>, or <i>POMGNT1</i>, reported AIAW. These events typically occurred in children <7 years old, and the preceding illness usually included respiratory symptoms. In 10 (47.6%) patients with DG, AIAW preceded the diagnosis of muscular dystrophy. People with DG, across genotypes, can experience acute, transient weakness associated with a febrile illness, a phenomenon that rarely occurs in DBMD. The physiologic basis of this phenomenon is unknown. NCT00313677.