Cardiomyopathy in Patients with FKRP Mutations


Real World Data - Disease registries, natural history, post marketing surveillance

Poster Number: 154


Eric Libell, MD student, Julia Richardson, Katie Lutz, Benton Ng, Shelley Mockler, PT, DSc, Katie Laubscher, Carrie Stephan, Bridget Zimmerman, Erik Edens, Bemjamin Reinking, katherine Mathews, MD


1. University of Iowa, 2. University of Iowa, 3. University of Iowa, 5. University of Iowa, 6. University of Iowa, 7. University of Iowa, 8. University of Iowa, 9. University of Iowa, 10. University of Iowa, 11. University of Iowa

Objective: To describe the frequency and age at onset of abnormal echocardiograms in a cohort of patients with mutations in FKRP. Background: The dystroglycanopathies (DGs), caused by mutations in one of 18 known genes, are autosomal recessive muscular dystrophies that share hypoglycosylation of a-dystroglycan. The DGs range from severe congenital muscular dystrophy to limb-girdle muscular dystrophy. The largest subgroup of DGs results from mutations in FKRP (LGMDR9). Reported frequencies of cardiomyopathy in LGMDR9 are varied. Methods: All available echocardiogram reports and/or films done for clinical indications on participants in a DG natural history study ( NCT00313677) with mutations in FKRP were collected and retrospectively reviewed. All echocardiograms were classified as normal (EF >55%; SF ≥ 28% for patients aged 15 years and older, 31-41% for patients aged 4-14 years, 33-43% for patients aged 2-3 years, and 35-45% for infants; normal wall motion) or abnormal. The probability of developing an abnormal echocardiogram was assessed by Kaplan-Meier analysis. Results: Of 269 echocardiograms on 56 subjects, at least one abnormal echocardiogram occurred in 25 subjects (44.6%). Median age at first abnormal echocardiogram for the whole cohort was 33.25 years (95% CI: 17.98, 54.21). Median age at first abnormal echocardiogram for subjects homozygous for the c.826C>A variant was 54.21 years (95% CI 39.67, 54.21) compared to median age for all other FKRP genotypes of 15.44 years (95% CI: 14.31, 18.06), p<0.0001. The earliest age at first abnormal echocardiogram was 3 years. There was no significant difference in cardiomyopathy onset by sex. Conclusions: Cardiomyopathy is prevalent in those with FKRP mutations. While the median onset is in mid-adulthood, it can present in childhood. Genotype influences age at onset; cardiomyopathy occurs later in subjects homozygous for the c.826C>A mutation. These data can help to guide surveillance frequency.