Electroretinogram abnormalities in FKRP-related limb-girdle muscular dystrophy (LGMDR9).

Abstract

Dystroglycanopathies are a heterogeneous group of membrane-related muscular dystrophies. The dystroglycanopathy phenotype includes a spectrum of severity ranging from severe congenital muscular dystrophy to adult-onset limb-girdle muscular dystrophy (LGMD). LGMDR9 is a dystroglycanopathy caused by mutations in the FKRP gene. Previous studies have characterized electroretinogram findings of dystroglycanopathy mouse models but have not been reported in humans. This study set out to characterize the electroretinogram in eight participants with LGMDR9. Eight participants were recruited from an ongoing dystroglycanopathy natural history study at the University of Iowa (NCT00313677). Inclusion criteria for the current study were children and adults > 6years old with confirmed LGMDR9. Age similar controls were identified from our electrophysiology service normative control database. Full-field electroretinograms were recorded using ISCEV standards. Six of the eight participants underwent light-adapted ON/OFF testing. The electronegative electroretinogram was not seen in any participants with LGMDR9. An unusual sawtooth pattern in the 30Hz flicker with faster rise than descent was noted in all 8 participants. Our cases showed a decreased b-wave amplitude in light-adapted ON responses (p = 0.011) and decreased d-wave amplitude in light-adapted OFF responses (p = 0.015). Decreased b-wave amplitude in light-adapted 3.0testing (p = 0.015) and decreased flicker ERGamplitudes were also detected (p = 0.0018). Additionally, compared to controls, participants with LGMDR9 had decreased a-wave amplitudes on dark-adapted 10testing (p = 0.026). Abnormal ON/OFF bipolar cell responses and sawtooth 30Hz flicker waveforms on full-field electroretinogram may be specific for LGMDR9. If confirmed in a larger population and if related to disease stage, these tests are potential biomarkers which could be useful as endpoints in clinical treatment trials.