Predicting Loss of Ambulation in Limb Girdle Muscular Dystrophy R9

Chandra L. Miller; Lauren N. Coffey; Shelley R. H. Mockler; Katie M. Laubscher; Carrie M. Stephan; M. Bridget Zimmerman; Katherine D. Mathews

doi:10.1002/acn3.70299

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Predicting Loss of Ambulation in Limb Girdle Muscular Dystrophy R9

Journal article

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Predicting Loss of Ambulation in Limb Girdle Muscular Dystrophy R9

Chandra L. Miller, Lauren N. Coffey, Shelley R. H. Mockler, Katie M. Laubscher, Carrie M. Stephan, M. Bridget Zimmerman and Katherine D. Mathews

Annals of clinical and translational neurology

01/04/2026

DOI: 10.1002/acn3.70299

PMCID: PMC13251427

PMID: 41486779

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Abstract

Background Limb girdle muscular dystrophy type R9 (LGMDR9) results from biallelic variants in FKRP. There is limited data to predict loss of ambulation (LOA) among those with LGMDR9. Methods Participants in an ongoing dystroglycanopathy natural history study (NCT00313677) with FKRP variants who had achieved ambulation and were more than 3 years old were included (n = 97). LOA was defined as self-reported full-time wheelchair use, weakness preventing completion of the 10-m walk-run test (10MWT) or 10MWT time > 30 s. Interval-censored time-to-event analysis was used to determine median age at LOA. Receiver operating characteristic curves were used to examine the ability of 10MWT and 4-stair climb (4SC) times to predict LOA. Results Of 97 participants, 55 (57%) were homozygous for the c.826C>A founder variant. Thirty-one participants lost ambulation; 15 (49%) were homozygous for c.826C>A. Earliest age at LOA was 9 years (non-homozygous for c.826C>A). Median age at LOA for the cohort was 46.0 years. Performances on 10MWT and 4SC were highly predictive of LOA within 3 years, with areas under the ROC curve of 0.89 (10MWT) and 0.87 (4SC) when genotype was included in analysis. Optimal cutoffs for predicting LOA within 3 years differed by genotype and had acceptable sensitivity and specificity. Discussion LOA among those with LGMDR9 is strongly predicted by performance on 10MWT and 4SC. These results demonstrate the real-world significance of standardized motor function tests used in LGMDR9 clinical trials and aid in anticipatory guidance.

dystroglycanopathy

FKRP

limb-girdle muscular dystrophy

loss of ambulation

UIOWA OA Agreement

Details

Title: Subtitle: Predicting Loss of Ambulation in Limb Girdle Muscular Dystrophy R9
Creators: Chandra L. Miller - University of Iowa
Lauren N. Coffey - University of Iowa
Shelley R. H. Mockler - University of Iowa Health Care
Katie M. Laubscher - University of Iowa
Carrie M. Stephan - University of Iowa
M. Bridget Zimmerman - University of Iowa
Katherine D. Mathews - University of Iowa
Resource Type: Journal article
Publication Details: Annals of clinical and translational neurology
DOI: 10.1002/acn3.70299
PMID: 41486779
PMCID: PMC13251427
NLM abbreviation: Ann Clin Transl Neurol
ISSN: 2328-9503
eISSN: 2328-9503
Publisher: Wiley
Grant note: National Institutes of Health: NIH U54 NS053672
This work was supported by the National Institutes of Health, NIH U54 NS053672.
Language: English
Electronic publication date: 01/04/2026
Academic Unit: Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Biostatistics; Physical Therapy and Rehabilitation Science; Neurology (Pediatrics)
Record Identifier: 9985116168502771

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