Diagnostic journey for people with FKRP mutations participating in a dystroglycanopathy natural history study (n = 68; NCT00313677) was analyzed. Earliest symptoms and age at muscular dystrophy diagnosis were abstracted from subject-reported medical history and record review. Initial signs/symptoms were classified as chronic motor dysfunction (e.g., delayed motor milestones, weakness, falling; n = 40, 59%), elevated transaminases (n = 7, 10%), or acute/intermittent symptoms (myoglobinuria, myalgia, febrile illness-associated acute weakness; n = 21, 31%). Median time from sign/symptom onset to diagnosis was 6.5 years and differed by symptom group: 7.5 years for motor group, 9 years for acute/intermittent group, and 4 years for elevated transaminases group. The sign/symptom category that most commonly resulted in a diagnosis was chronic motor dysfunction (n = 45). Of those without clear weakness as first symptom (n = 55), 36.4% were not diagnosed with MD until weakness became apparent. Median time to diagnosis was shortest for those with febrile illness-associated acute weakness (0.25 years). Median time from first sign/symptom to MD diagnosis has decreased incrementally from 18.8 years for those with onset in the 1970s to < 10 years for symptom onset occurring after 2000. Awareness of disease presentation variability will aid in earlier diagnosis, which is increasingly important with treatments in development.
Keywords: Diagnosis; Diagnostic delay; Dystroglycanopathy; FKRP; Limb-girdle muscular dystrophy; Weakness.
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