Prospective observational study of FKRP-related limb-girdle muscular dystrophy R9: A GRASP consortium study

Lindsay N Alfano; Meredith K James; Kristine Grosfjeld Petersen; Karen Rudolf; John Vissing; Renee Augsburger; Tahseen Mozaffar; Aileen Jones; Amanda Butler; Katie M Laubscher; Shelley R H Mockler; Katherine D Mathews; Megan A Iammarino; Natalie F Reash; Lindsay Pietruszewski; Linda P Lowes; Talia Strahler; Matthew Wicklund; Stephanie Hunn; Conrad C Weihl; Sandhya Sasidharan; Melissa Currence; Jeffrey M Statland; Nikia Stinson; Megan Holzer; Doris G Leung; Donovan J Lott; Peter B Kang; Scott Holsten; Urvi Desai; Nicholas E Johnson; GRASP‐LGMD Consortium

doi:10.1002/acn3.52276

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Prospective observational study of FKRP-related limb-girdle muscular dystrophy R9: A GRASP consortium study

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Prospective observational study of FKRP-related limb-girdle muscular dystrophy R9: A GRASP consortium study

Lindsay N Alfano, Meredith K James, Kristine Grosfjeld Petersen, Karen Rudolf, John Vissing, Renee Augsburger, Tahseen Mozaffar, Aileen Jones, Amanda Butler, Katie M Laubscher, …

Annals of clinical and translational neurology, Vol.12(2), pp.332-344

02/2025

DOI: 10.1002/acn3.52276

PMCID: PMC11822816

PMID: 39675022

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Abstract

Limb-girdle muscular dystrophy R9 (LGMDR9, formerly known as LGMD2I), caused by variants in the fukutin-related protein (FKRP) gene leads to progressive muscle weakness of the shoulder and pelvic limb-girdles and loss of motor function over time. Clinical management and future trial design are improved by determining which standardized clinical outcome assessments (COA) of function are most appropriate to capture disease presentation and progression, informing endpoint selection and enrollment criteria. The purpose of our study was to evaluate the cross-sectional validity and reliability of clinical outcome assessments in patients with FKRP-related LGMDR9 participating in the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP) natural history study. Enrolled patients completed a battery of COA on two consecutive days, including the North Star Assessment for limb girdle-type dystrophies (NSAD), the 100-m timed test (100 m), and the Performance of Upper Limb 2.0 (PUL). A total of 101 patients with FKRP-related LGMDR9 completed COA evaluations. All functional COA were highly and significantly correlated even across constructs, except for the 9-hole peg test. Similarly, all tests demonstrated excellent test-retest reliability across 2-day visits. The NSAD and PUL demonstrate robust psychometrics with good targeting, ordered response thresholds, fit and stability, and limited dependency of items across the scales. This study has determined the suitability of several functional COA, cross-sectionally, in LGMDR9 to inform future trial design and clinical care.

Details

Title: Subtitle: Prospective observational study of FKRP-related limb-girdle muscular dystrophy R9: A GRASP consortium study
Creators: Lindsay N Alfano - The Ohio State University
Meredith K James - Newcastle University
Kristine Grosfjeld Petersen - University of Copenhagen
Karen Rudolf - University of Copenhagen
John Vissing - University of Copenhagen
Renee Augsburger - University of California, Irvine
Tahseen Mozaffar - University of California, Irvine
Aileen Jones - Virginia Commonwealth University
Amanda Butler - Virginia Commonwealth University
Katie M Laubscher - University of Iowa
Shelley R H Mockler - Center for Disabilities and Development, University of Iowa Health Care Stead Family Children's Hospital, Iowa City, Iowa, USA
Katherine D Mathews - University of Iowa
Megan A Iammarino - Nationwide Children's Hospital
Natalie F Reash - Nationwide Children's Hospital
Lindsay Pietruszewski - Nationwide Children's Hospital
Linda P Lowes - The Ohio State University
Talia Strahler - University of Colorado Anschutz Medical Campus
Matthew Wicklund - University of Colorado Anschutz Medical Campus
Stephanie Hunn - Washington University in St. Louis School of Medicine
Conrad C Weihl - Washington University in St. Louis School of Medicine
Sandhya Sasidharan - University of Kansas Medical Center
Melissa Currence - University of Kansas Medical Center
Jeffrey M Statland - University of Kansas Medical Center
Nikia Stinson - Kennedy Krieger Institute
Megan Holzer - Kennedy Krieger Institute
Doris G Leung - Johns Hopkins Medicine
Donovan J Lott - University of Florida
Peter B Kang - University of Florida
Scott Holsten - Department of Neurology, Atrium Health, Charlotte, North Carolina, USA
Urvi Desai - Department of Neurology, Atrium Health, Charlotte, North Carolina, USA
Nicholas E Johnson - Virginia Commonwealth University
GRASP‐LGMD Consortium
Resource Type: Journal article
Publication Details: Annals of clinical and translational neurology, Vol.12(2), pp.332-344
DOI: 10.1002/acn3.52276
PMID: 39675022
PMCID: PMC11822816
NLM abbreviation: Ann Clin Transl Neurol
ISSN: 2328-9503
eISSN: 2328-9503
Publisher: WILEY
Grant note: ML Bio Solutions
Language: English
Electronic publication date: 12/15/2024
Date published: 02/2025
Academic Unit: Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Physical Therapy and Rehabilitation Science; Neurology (Pediatrics)
Record Identifier: 9984757685102771

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