Abstract
Variants in the FKRP (Fukutin-related protein) gene result in a slowly progressive neuromuscular disease called FKRP-related limb-girdle muscular dystrophy or LGMDR9. Several potential disease-modifying therapies have now entered clinical trials for LGMDR9 (NCT05224505, NCT05230459), so there is a fundamental need for internationally agreed upon standards of care (SOC) guidelines. SOC guidelines are a framework to assist clinicians providing appropriate and safe management of patients. Moreover, their implementation facilitates interpretation of clinical research results by ensuring similar baseline care for patients across trial sites, particularly important in a rare disease requiring international sites. Experts in LGMDR9 collaborated in a series of online workshops to present, review, and discuss published evidence in the disease. They covered topics including diagnosis; outcome measures; cardiac and respiratory function; nutrition and weight; pain; fatigue; exercise; psychosocial care; surgery; emergency care and advanced care planning; and pregnancy. Following the online discussions, the experts had a face-to-face meeting to develop provisional recommendations in the aforementioned areas. Evidence from several recent natural history studies in LGMDR9 informed the guidelines (NCT04001595) [1-4]. The experts agreed that LGMDR9 should be suspected in patients with autosomal recessive LGMD, high CK levels, and common clinical features such as proximal and calf hypertrophy. Detection of pathogenic mutations in both alleles of the FKRP gene via direct sequencing or next generation sequencing (NGS) is the only definitive way to diagnose LGMDR9; muscle biopsy and muscle MRI can help guide the diagnosis. Cardiac and respiratory involvement is common so should be monitored and managed proactively [5]. Physiotherapy and input from occupational therapists can help maximise motor function and minimise the impact on daily living by using outcome measures to inform forward planning. A significant number of patients will experience pain, fatigue, and psychosocial concerns; clinicians should address these aspects when symptoms impact daily living and provide support where indicated.
Acknowledgements: We are grateful to the MDA, the AFM, MDUK, The Speak Foundation, LGMD2i Research Fund, CureLGMD2i Foundation, Ask Bio, Atamyo, and MLBio Solutions for their support for this workshop.