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

Joshua L Hagedorn; Taylor M Dunn; Sajag Bhattarai; Carrie Stephan; Katherine D Mathews; Wanda Pfeifer; Arlene V Drack

doi:10.1007/s10633-022-09909-4

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

Journal article

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

Joshua L Hagedorn, Taylor M Dunn, Sajag Bhattarai, Carrie Stephan, Katherine D Mathews, Wanda Pfeifer and Arlene V Drack

Documenta ophthalmologica, Vol.146(1), pp.7-16

02/2023

DOI: 10.1007/s10633-022-09909-4

PMID: 36399172

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https://www.ncbi.nlm.nih.gov/pmc/articles/11171413View

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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.

Details

Title: Subtitle: Electroretinogram abnormalities in FKRP-related limb-girdle muscular dystrophy (LGMDR9)
Creators: Joshua L Hagedorn - Roy J. and Lucille A. Carver College of Medicine
Taylor M Dunn - University of Alabama at Birmingham
Sajag Bhattarai - Visual Sciences
Carrie Stephan - University of Iowa
Katherine D Mathews - University of Iowa
Wanda Pfeifer - Visual Sciences
Arlene V Drack - Roy J. and Lucille A. Carver College of Medicine
Resource Type: Journal article
Publication Details: Documenta ophthalmologica, Vol.146(1), pp.7-16
DOI: 10.1007/s10633-022-09909-4
PMID: 36399172
NLM abbreviation: Doc Ophthalmol
ISSN: 0012-4486
eISSN: 1573-2622
Grant note: name: Ronald Keech Professorship; name: University of Iowa ERG Fund; DOI: 10.13039/100001818, name: Research to Prevent Blindness; name: Iowa Wellstone Muscular Dystrophy Cooperative Research Center, award: U54 NS053672
Language: English
Electronic publication date: 11/18/2022
Date published: 02/2023
Academic Unit: Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics); Ophthalmology and Visual Sciences
Record Identifier: 9984319258802771

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