Progression to Loss of Ambulation Among Patients with Autosomal Recessive Limb-girdle Muscular Dystrophy: A Systematic Review

J Neuromuscul Dis. 2022;9(4):477-492. doi: 10.3233/JND-210771.

PMID: 35527561

Ivana F Audhya, Antoinette Cheung, Shelagh M Szabo

Highlights: This review illustrated that patients with early childhood-onset disease tend to have faster progression to loss of ambulation than those with late childhood- or adult-onset disease, particularly in LGMDR9.

Abstract

Background: The effect of age at the onset of autosomal recessive limb girdle muscular dystrophy (LGMDR) on the development of loss of ambulation (LOA), particularly by subtype, is not well understood.

Objectives: To characterize the prevalence and timing of LOA and to describe the characteristics of patients with adult, late childhood, and early childhood onset LGMDR by subtype.

Methods: A systematic review of MEDLINE, Embase, and the Cochrane library was done. Data from published sources were combined to determine the frequency and timing of LOA in individuals with LGMDR1, LGMDR2/Miyoshi myopathy (MM), LGMDR3-6, LGMDR9, and LGMDR12.

Results: Among patients with a documented age at onset (n = 1,603) in 195 studies, 695 (43.4%) had adult-, 532 (33.2%) late childhood-, and 376 (23.5%) early childhood-onset disease; the distribution of age at onset differed amongst subtypes. Among patients with LOA (n = 228), adult-onset disease was uncommon in LGMDR3-6 (14%) and frequent in LGMDR2/MM (42%); LGMDR3-6 cases with LOA primarily had early childhood-onset (74%). Mean (standard deviation [SD]) time to LOA was shortest for patients with early childhood-onset LGMDR9 (12.0 [4.9] years, n = 19) and LGMDR3-6 (12.3 [10.7], n = 56) and longest for those with late childhood-onset LGMDR2/MM (21.4 [11.5], n = 36). The mean time to LOA varied between subtypes.

Conclusions: In particular for LGMDR9, this research demonstrated that patients with early childhood onset disease likely to develop to LOA more quickly than those with late childhood or adult onset disease. These findings offer a better knowledge of how each LGMDR subtype contributes to the development of LOA, which may assist guide the design of clinical trials and serve as a foundation for natural history investigations.

Keywords: Muscular dystrophies, age of onset, disease progression, limb-girdle, systematic review