Affiliation:
1. Sarepta Therapeutics Inc, Cambridge MA, USA
2. Broadstreet HEOR, Vancouver, BC, V6A 1A4 Canada
3. Washington University School of Medicine, St. Louis, MO, USA
Abstract
Background The impact of age at autosomal recessive limb girdle muscular dystrophy (LGMDR) onset on progression to loss of ambulation (LOA) has not been well established, particularly by subtype. Objectives: To describe the characteristics of patients with adult-, late childhood-, and early childhood-onset LGMDR by subtype and characterize the frequency and timing of LOA. Methods: A systematic review was conducted in MEDLINE, Embase and the Cochrane library. Frequency and timing of LOA in patients with LGMDR1, LGMDR2/Miyoshi myopathy (MM), LGMDR3-6, LGMDR9, and LGMDR12 were synthesized from published data. Results: In 195 studies, 695 (43.4%) patients had adult-, 532 (33.2%) had late childhood-, and 376 (23.5%) had early childhood-onset of disease across subtypes among those with a reported age at onset (n = 1,603); distribution of age at onset varied between 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 varied between subtypes and 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). Conclusions: This review illustrated 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. These findings provide a greater understanding of progression to LOA by LGMDR subtype, which may help inform clinical trial design and provide a basis for natural history studies.
Subject
Neurology (clinical),Neurology
Reference204 articles.
1. Limb-girdle muscular dystrophy: Diagnostic evaluation, frequency and clues to pathogenesis;Lo;Neuromuscular Disorders,2008
2. The Limb-Girdle Muscular Dystrophies: Is Treatment on the Horizon?;Chu;Neurotherapeutics,2018
3. Prevalence, pathological mechanisms, and genetic basis of limb-girdle muscular dystrophies: A review;Taghizadeh;J Cell Physiol,2019
4. Genetic basis of limb-girdle muscular dystrophies: The update;Nigro;Acta Myol,2014
5. The Limb-Girdle Muscular Dystrophies and the Dystrophinopathies;Iyadurai;Continuum (Minneap Minn),2016
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献