Abstract
SP44 Advancing the understanding of clinical phenotypes using standardized outcome assessments: Insights from the GRASP consortium
Neuromuscular disorders : NMD, Vol.67(Suppl 1), 107349
09/29/2026
DOI: 10.1016/j.nmd.2026.107349
Abstract
The rarity and geographic dispersion of genetically inherited muscle diseases make it difficult to establish a comprehensive understanding of their clinical manifestations and functional trajectories. The limb-girdle muscular dystrophies (LGMDs) exemplify this challenge, comprising over 30 subtypes with substantial genetic and phenotypic heterogeneity. Since 2018, the Genetic Resolution and Assessments Solving Phenotypes (GRASP) consortium has established a 15-site international network to characterize disease phenotypes and support clinical trial readiness. To date, 216 participants have been enrolled, including LGMD R1 (n=45), R2 (n=8), R3–6 (n=30), R9 (n=100), R12 (n=18), D1 (n=15), and Becker muscular dystrophy (n=46). Longitudinal assessments were conducted using standardized clinical outcome assessments (COAs) including but not limited to the North Star Assessment for limb girdle type muscular Dystrophies (NSAD), North Star Ambulatory Assessment (NSAA), 100-meter timed test (100m), 10 meter walk/run (10m), other timed function tests, and Performance of Upper Limb v2.0 (PUL). Analyses of performance relative to age and disease duration, alongside item-level changes, reveal emerging patterns of subtype-specific functional progression. Cohort-level analyses further enable the identification of potential predictors of skill loss, which may substantially improve clinical management through anticipatory guidance and preparation for transitions in functional status. Notably, across all cohorts, those completing the 10m in 7.1-11.1 seconds or less (0.9-1.4 m/s) retained the ability to rise independently from the floor, suggesting a clinically meaningful functional threshold. Similar to Duchenne muscular dystrophy (DMD), individuals with BMD demonstrate a comparable pattern of functional decline and skill loss, albeit at a slower rate of progression. In contrast, individuals with a sarcoglycanopathy (LGMD R3–6) exhibit early proximal upper extremity weakness while remaining ambulatory, differing from DMD in which significant upper extremity involvement typically follows loss of ambulation. In LGMD R12 (predominantly homozygous cohort), independent standing and ambulation are preserved despite earlier loss of transitional movements such as rising from a chair, sitting up in bed, and rolling supine to prone. Further, upper limb weakness as measured by PUL, appears to emerge much later in disease progression often well after the initiation of regular power wheelchair use. Additional findings that highlight subtype-specific trajectories will be presented.
Details
- Title: Subtitle
- SP44 Advancing the understanding of clinical phenotypes using standardized outcome assessments: Insights from the GRASP consortium
- Creators
- Megan Iammarino - The University of Texas at San Antonio Health Science CenterMichael Kiefer - Virginia Commonwealth UniversityStacy Dixon - University of Colorado DenverDoris Leung - Kennedy Krieger InstituteLinda Lowes - Nationwide Children's HospitalPeter Kang - University of MinnesotaKatherine Mathews - University of IowaTahseen Mozaffar - University of California, IrvineJeffrey Statland - University of Kansas Medical CenterConrad Weihl - Washington University Sch Med, St. Louis, USAMatthew Wicklund - The University of Texas at San Antonio Health Science CenterJennifer Raymond - Virginia Commonwealth UniversityRuby Langeslay - Virginia Commonwealth UniversityLindsay Alfano - Nationwide Children's HospitalNicholas Johnson - Virginia Commonwealth University
- Resource Type
- Abstract
- Publication Details
- Neuromuscular disorders : NMD, Vol.67(Suppl 1), 107349
- DOI
- 10.1016/j.nmd.2026.107349
- ISSN
- 0960-8966
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 09/29/2026
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9985241831202771
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