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

Doc Ophthalmol. 2023 Feb;146(1):7-16. doi: 10.1007/s10633-022-09909-4. Epub 2022 Nov 18.

Abstract

Background: 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.

Purpose: This study set out to characterize the electroretinogram in eight participants with LGMDR9.

Methods: 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 > 6 years 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.

Results: The electronegative electroretinogram was not seen in any participants with LGMDR9. An unusual sawtooth pattern in the 30 Hz 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 3.0 testing (p = 0.015) and decreased flicker ERG amplitudes were also detected (p = 0.0018). Additionally, compared to controls, participants with LGMDR9 had decreased a-wave amplitudes on dark-adapted 10 testing (p = 0.026).

Conclusions: Abnormal ON/OFF bipolar cell responses and sawtooth 30 Hz 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.

Keywords: Amplitudes; Dystroglycanopathy; Dystrophy; Electronegative; Electroretinogram; FKRP; LGMDR9; Limb–girdle muscular dystrophy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Child
  • Electroretinography*
  • Humans
  • Mice
  • Muscular Dystrophies, Limb-Girdle* / diagnosis
  • Muscular Dystrophies, Limb-Girdle* / epidemiology
  • Muscular Dystrophies, Limb-Girdle* / genetics
  • Mutation
  • Pentosyltransferases / genetics
  • Phenotype

Substances

  • FKRP protein, human
  • Pentosyltransferases
  • Fkrp protein, mouse

Supplementary concepts

  • Muscular Dystrophy, Limb-Girdle, Type 2I

Associated data

  • ClinicalTrials.gov/NCT00313677