Describe the diagnostic odyssey of patients with Fukutin-Related Protein (FKRP)-associated muscular dystrophy (MD) to identify barriers to diagnosis.

Dystroglycanopathies are MDs characterized by hypoglycosylation of alpha-dystroglycan. The most common dystroglycanopathy results from mutations in FKRP. Persistent diagnostic delay is reported in several neuromuscular diseases.

All participants in an ongoing dystroglycanopathy natural history study (NCT00313677) with FKRP mutations were included. Earliest symptoms, symptoms prompting evaluation, and age at MD diagnosis (independent of subtype) were abstracted from patient-reported medical history supplemented by medical record review.

68 subjects were included. Self-reported initial symptoms were classified as motor dysfunction (missed milestones, weakness, falling, etc.; n=40, 59%), incidental transaminitis (n=7, 10%), and “metabolic” (myoglobinuria, pain, febrile illness-associated acute weakness; n=21, 31%). Median age at symptom onset was 6 years for motor group,  9 years for “metabolic” group, and 4 years for transaminitis group. The median time from symptom onset to MD diagnosis was 6.5 years; motor group was 7.5 years, “metabolic” group was 9 years, and transaminitis group was 4 years. The symptom that most commonly resulted in an MD diagnosis was motor dysfunction (n=45). For those without clear weakness as first symptom (n=55), 36.4% were not diagnosed until weakness became apparent. Median time to MD diagnosis was shortest for those with febrile illness-associated acute weakness (0.25 years) and missed milestones (1.5 years). Median time from first symptom to MD diagnosis has decreased incrementally from 18.8 years for those with childhood symptom onset in the 1970s to < 10 years if symptom onset occurred after 1990. 

While our data suggests decreasing diagnostic delay over decades, time from symptom onset to MD diagnosis was still several years in our cohort. Awareness of disease presentation variability will aid in earlier diagnosis, which is increasingly important with treatments in development.