We sought to delineate the full phenotypic spectrum and characterize the natural history of limb girdle muscular dystrophy-D1 (LGMD-D1) through a combination of systematic literature review, retrospective chart review, and a cross sectional observational study with a subset of longitudinal assessments.

We extracted demographics and age at clinical events of interest contributing to LGMD-D1 disease burden, such as cardiac, respiratory, and swallowing abnormalities, as well as loss of ambulation from systematically identified case reports, case series, and LGMD-D1 patient charts. We determined the frequency of events and used survival analyses to estimate median time from onset to clinical events. When available, manual muscle testing and quantitative dynamometry were utilized to estimate muscle specific rates of strength decline. Retrospective analyses were complemented with a cross sectional observational study including the Measure of Activity Limitations (ACTIVLIM) and a customized LGMD-D1 questionnaire, cataloging patients’ ages at clinical events of interest. Longitudinal assessments were completed 1.5 years apart in a subset of patients. All data was assessed for differences between males and females, proximal and distal predominant phenotypes, as well as genotype specific changes.

At time of submission, 115 LGMD-D1 patients were included. This study is the largest description of LGMD-D1 patients to date.  Overall, this data highlights key genotype - phenotype differences among LGMD-D1 patients, including age of disease onset, progression to loss of ambulation, and weakness patterns.