Objective: To characterize the frequency of loss of ambulation (LOA) among patients with LGMDR, and progression to cardiac and respiratory abnormalities among those with and without LOA.
Background: Patients with LGMDR may experience muscle weakness progressing to severe impairments affecting their mobility, cardiac function, and respiratory function. The clinical course of LGMDR is highly variable; some patients have rapid onset and early progression with significant morbidity such as LOA.
Methods: A systematic review was conducted using MEDLINE and EMBASE focusing on the most common LGMDR subtypes: LGMDR1, LGMDR2/Miyoshi myopathy (MM), LGMDR3-6, LGMDR9, LGMDR12. Data were derived from cohort studies and case reports. Outcomes of interest were number and percentage n(%) of patients with vs. without LOA who experienced cardiac or respiratory abnormalities, and mean (standard deviation, SD) age at LOA, cardiac, and respiratory abnormalities.
Results: From 2,929 abstracts screened, 418 patients were identified with data on ambulatory status. LOA was reported in 265 (63.4%), and case counts by subtype ranged from 5 (LGMDR12) to 105 (LGMDR3-6). Thirty-four percent (n=142) of patients with LOA had reports of cardiac and/or respiratory function status. Among these patients, respiratory abnormalities were most frequent in LGMDR3-6 (74.1%); and cardiac, in LGMDR9 (73.3%). The mean (SD) age at cardiac abnormalities was earliest in LGMDR9 (23.7 [17.7] years; in 73.3%); and respiratory abnormalities, earliest in LGMDR3-6 (23.9 [11.0] years; in 74.1%). Abnormalities were less common in patients without LOA except in LGMDR9, where abnormalities remained frequent (71.4% respiratory, 52.4% cardiac).
Conclusions: This study described the co-occurrence of LOA, cardiac, and respiratory abnormalities in LGMDR. Caution should be taken when interpreting summary estimates as these are impacted by the frequency of underlying genotypes; an additional limitation is that data derived from case reports lack standardized reporting. Despite limited data, these findings help characterize the clinical progression of LGMDR.