Objective: To characterize the time from disease onset to LOA among patients with LGMDR.
Background: Patients with LGMDR predominantly present with proximal muscle weakness; severity varies widely between patients. Progression to severe mobility impairments such as LOA has been described; however, it is unclear how the occurrence and timing of LOA compares between subtypes and by age at onset.
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 frequency of and mean (standard deviation [SD]) time from onset to LOA among those with adult-, late childhood- (10-18 years), and early childhood-onset LGMDR (<10 years).
Results: From 2,929 abstracts, 375 patients were identified with age at LGMD onset and ambulatory status reported, with case counts ranging from 20 (LGMDR12) to 113 (LGMDR2/MM). Among patients with LOA (n=228), adult-onset disease was least common in LGMDR3-6 (1.5%) and most common in LGMDR2 (46.5%); LGMDR3-6 cases with LOA primarily had early childhood-onset (84.8%). Mean (SD) time to LOA varied between subtypes, being shortest for patients with early childhood-onset LGMDR9 (12.0 [4.9] years, n=19) and longest for those with late childhood-onset LGMDR2 (21.5 [12.5] years, n=21).
Conclusions: These findings suggest that patients with early childhood-onset disease tend to have faster progression to LOA than those with late childhood- or adult-onset disease, particularly in LGMDR9. Caution should be taken when interpreting summary estimates as these are impacted by the frequency of the underlying genotypes; an additional limitation is that data derived from case reports lack standardized reporting. Nevertheless, these findings provide a greater understanding of progression to LOA by subtype in LGMDR.