Wheelchair use in genetically confirmed FSHD1 from a large cohort study in Chinese population

Qiu, Liangliang; Chen, Long; Zheng, Fuze; Lin, Min-Ting; Lin, Yi‐Han; Fu, Ying; Wang, Ning; Wang, Zhi-Qiang

doi:10.1093/brain/awac097

Cited by 7 publications

(6 citation statements)

References 6 publications

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“…Among patients with FSHD1 carrying fewer (1-3) D4Z4 RU (n = 231), CpG6 hypomethylation was mild or modest and significantly correlated with onset age of first-ever muscle weakness (Spearman r = 0.371, p < 0.001), CS (Spearman r = -0.347, p < 0.001), and ACSS (Spearman r = -0.503, p < 0.001). Similarly, CpG6 methylation level was also significantly correlated with onset age of first-ever muscle weakness, CS, and ACSS in patients with FSHD1 carrying an intermediate (4)(5)(6) or large (7-9) D4Z4 RU number (eTable 3, links.lww.com/WNL/C846).…”

Section: Kruskal-wallismentioning

confidence: 90%

“… 3 Wheelchair dependency was defined based as an mRS of grade 4–5 and a CSS of 4.5–5 (wheelchair use for most activities or wheelchair bound). 4 Yearly follow-ups were conducted through outpatient service, telephone survey, or remote video conferences performed by the same neurologist (Z.Q.W.).…”

Section: Methodsmentioning

confidence: 99%

“… 2 Ultimately, FSHD1 can lead to disability with loss of independent ambulation 3 or even wheelchair dependence. 4 An American team recently reported the relatively high disability rate of 23.7% in their cohort. 5 In China, 12.0% of patients with genetically confirmed FSHD1 will likely lose independent ambulation within 40 years of first onset of muscle weakness; in this large-scale population studied by our group, the incidence of wheelchair reached 8.9%.…”

mentioning

confidence: 99%

“… 5 In China, 12.0% of patients with genetically confirmed FSHD1 will likely lose independent ambulation within 40 years of first onset of muscle weakness; in this large-scale population studied by our group, the incidence of wheelchair reached 8.9%. 3 , 4 The development of disability in FSHD1 may involve 3 processes, including lower extremity involvement, independent ambulation loss, and wheelchair dependence.…”

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confidence: 99%

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Association of 4qA-Specific Distal D4Z4 Hypomethylation With Disease Severity and Progression in Facioscapulohumeral Muscular Dystrophy

et al. 2023

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Objective:To examine whether the regional methylation levels at the most distal D4Z4 repeat units (RU) in the 4qA-permissive haplotype were associated with disease severity and progression in facioscapulohumeral muscular dystrophy type 1 (FSHD1).Methods:This was a 21-year, retrospective, and observational cohort study conducted at the Fujian Neuromedical Centre (FNMC) in China. Methylation levels of the most distal D4Z4 RU, including 10 CpGs, were assessed in all participants by bisulfite sequencing. FSHD1 patients were stratified into 4 groups based on methylation percentage quartiles, including LM1 (low methylation), LM2 (low to intermediate methylation), LM3 (intermediate to high methylation), and highest methylation levels (HM). Patients received evaluations of motor function focusing on lower extremity (LE) progression at baseline and in follow-ups. FSHD clinical score (CS), age-corrected clinical severity scale (ACSS), and modified Rankin Scale were used to assess motor function.Results:The methylation levels of the 10 CpGs were significantly lower in all 823 genetically confirmed FSHD1 patients than in 341 healthy controls (HCs). CpG6 methylation levels could distinguish: 1) FSHD1 patients from HCs; 2) symptomatic from asymptomatic/unaffected patients; 3) patients with LE involvement from those without LE involvement, with AUCs (95% CI) of 0.9684 (0.9584–0.9785), 0.7417 (0.6903–0.7931), and 0.6386 (0.5816–0.6956), respectively. CpG6 methylation levels were negatively correlated with both CS (r = -0.392) and ACSS (r = -0.432), and positively correlated with onset age of first-ever muscle weakness (r = 0.297). For the LM1, LM2, LM3, and HM groups, the respective proportions of LE involvement were 52.9%, 44.2%, 36.9%, and 23.4%; and onset ages of LE involvement were 20, 26.5, 25, and 26.5 years. Cox regression analysis—adjusted for sex, age at examination, D4Z4 RU, and 4qA/B haplotype—showed that the LM1, LM2, and LM3 groups (i.e., groups with lower methylation levels) had a higher risk for independent ambulation loss, with HRs (95% CI) of 3.523 (1.565–7.930), 3.356 (1.458–7.727), and 2.956 (1.245–7.020), respectively.Conclusion:4q35 distal D4Z4 hypomethylation is correlated with disease severity and progression to lower extremity involvement.

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Section: Kruskal-wallismentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Association of 4qA-Specific Distal D4Z4 Hypomethylation With Disease Severity and Progression in Facioscapulohumeral Muscular Dystrophy

et al. 2023

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“…However, the prevalence during 2001 to 2020 was probably underestimated in our previous publications. [37,38] Hence, we need to calculate a true prevalence rate and robust conclusions through implementation and execution a large, nationwide registry-based study in the future. In addition, CF1R allows for collection and analysis of longitudinal data, and next steps are to carry out an in-depth analysis on this and extended data, focusing on the biomarkers of progression.…”

Section: Discussionmentioning

confidence: 99%

The China facioscapulohumeral muscular dystrophy type 1 (FSHD1) registry: rationale for and description of a nationwide, observational cohort study

Qiu

Chen

Zheng

et al. 2022

Preprint

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Background: Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is a rare, hereditary, and progressive muscular dystrophy characterized by weakness and wasting of the facial (facio-) and shoulder-upper arm (scapulo-humeral-) muscles. The clinical severity varies from nonpenetrant/asymptomatic to disability with independent ambulation loss or even wheelchair dependence. Expansion of our knowledge of the genetic model D4Z4 macrosatellite repeat contraction leading to inappropriate expression of DUX4 has led to advances in developing targeted therapeutic strategies. Thus, clinical trial readiness is now required, particularly patient registry. However, there is no FSHD registry in China, let alone any database of the epidemiology, natural history, and clinical management of FSHD. This nationwide, longitudinal, non-interventional, rare-disease patient registry (The China FSHD1 Registry, CF1R ) was established to address the paucity of data in FSHD1 and to help inform future clinical practice and optimization clinical management. Results: This explorative study aims to recruit all patients with a genetically confirmed diagnosis of FSHD1 in China. Practice data, including demographic factors, disease progression history, family history, and clinical and genetic features are collected; the protocol does not mandate any interventions. Patients will be continuously assessed for 10 years at 5-year intervals. Several data analyses and peer-reviewed publications are expected to be generated throughout this period. Conclusions: The data collected within this rare-disease patient registry (CF1R) will be utilized to synthesize real-world data on epidemiological information, disease progression, and clinical and (epi)genetic information, which are vital for adequate symptom management and clinical trial-readiness of FSHD1 in China. Ethics and dissemination The study was granted ethics committee approval by the First Affiliated Hospital of Fujian Medical University (MRCTA, ECFAH of FMU [2020]026) in 2020. Findings will be disseminated via presentations and peer-reviewed publications. Dissemination will target different audiences, including national stakeholders, researchers from different disciplines and the general public. Trial registration number NCT04369209

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Management of FSHD symptoms: current assistive technologies and pharmacological approaches

Hitti,

Kavanaugh,

Zukotynski

et al. 2024

Disability and Rehabilitation: Assistive Technology

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Wheelchair use in genetically confirmed FSHD1 from a large cohort study in Chinese population

Cited by 7 publications

References 6 publications

Association of 4qA-Specific Distal D4Z4 Hypomethylation With Disease Severity and Progression in Facioscapulohumeral Muscular Dystrophy

Association of 4qA-Specific Distal D4Z4 Hypomethylation With Disease Severity and Progression in Facioscapulohumeral Muscular Dystrophy

The China facioscapulohumeral muscular dystrophy type 1 (FSHD1) registry: rationale for and description of a nationwide, observational cohort study

Management of FSHD symptoms: current assistive technologies and pharmacological approaches

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