van Ruitenbeek, E., Custers, J.A.E., Verhaak, C., Snoeck, M., Erasmus, C.E., Kamsteeg, E.J., Schouten, M.I., Coleman, C., Treves, S., Van Engelen, B.G., Jungbluth, H., and Voermans, N.C.
Highlights • RYR1-related myopathies are associated with functional impairments and chronic fatigue. • This accounts for congenital myopathies and to a lesser extent for malignant hyperthermia. • This results in substantial loss of quality of life. Abstract Mutations in RYR1 are a common genetic cause of non-dystrophic neuromuscular disorders. To obtain baseline data concerning the prevalence of fatigue, the psychological disease burden and quality of life associated with these common conditions, we performed a questionnaire study. Seventy-two patients were included in this study, 33 with a congenital myopathy and 39 with malignant hyperthermia or exertional rhabdomyolysis. Our results showed that patients with RYR1 -related myopathies have more functional impairments and significant chronic fatigue compared to healthy controls, with almost half of patients being severely fatigued. Whilst fatigue, pain and associated physical and social difficulties were more pronounced in those with permanent phenotypes, individuals with intermittent phenotypes also scored higher in all relevant categories compared to healthy controls. These findings indicate that RYR1 -related myopathies, despite being often considered relatively mild conditions, are nevertheless associated with severe fatigue and functional limitations, resulting in substantial loss of quality of life. Moreover, milder but in essence similar findings in patients with RYR1 -related malignant hyperthermia and rhabdomyolysis suggest that those phenotypes are not truly episodic but in fact associated with a substantial permanent disease burden. These preliminary data should help to design more comprehensive quality of life studies to inform standards of care. [ABSTRACT FROM AUTHOR]