A 5-year clinical follow-up study from the Italian National Registry for FSHD

Liliana Vercelli,Elena Pegoraro,Silvia Tripodi,Tiziana Mongini,Giovanni Antonini,Giuliano Tomelleri,Elisabetta Bucci,Giulia Ricci,Massimiliano Filosto,Antonio Di Muzio,Antonio Vallarola,Gabriele Siciliano,Louise Maranda,Maurizio Moggio,Lorenzo Maggi,Marina Scarlato,Carmelo Rodolico,Corrado Angelini,Monica Govi,Lucio Santoro,Fabiano Mele,Stefano C Previtali ,Lucia Ruggiero,Angela Berardinelli,Francesco Sera,Luísa Villa ,Rossella Tupler

doi:10.1007/s00415-020-10144-7

Abstract

BackgroundThe natural history of facioscapulohumeral muscular dystrophy (FSHD) is undefined.MethodsAn observational cohort study was conducted in 246 FSHD1 patients. We split the analysis between index cases and carrier relatives and we classified all patients using the Comprehensive Clinical Evaluation Form (CCEF). The disease progression was measured as a variation of the FSHD score performed at baseline and at the end of 5-year follow-up (ΔFSHD score).FindingsDisease worsened in 79.4% (112/141) of index cases versus 38.1% (40/105) of carrier relatives and advanced more rapidly in index cases (ΔFSHD score 2.3 versus 1.2). The 79.1% (38/48) of asymptomatic carriers remained asymptomatic. The highest ΔFSHD score (1.7) was found in subject with facial and scapular weakness at baseline (category A), whereas in subjects with incomplete phenotype (facial or scapular weakness, category B) had lower ΔFSHD score (0.6) p < 0.0001.ConclusionsThe progression of disease is different between index cases and carrier relatives and the assessment of the CCEF categories has strong prognostic effect in FSHD1 patients.

Highlights

Facioscapulohumeral muscular dystrophy (FSHD, OMIM # 158900) is a hereditary myopathy with prevalence of 1 in 8500–20,000 individuals [1, 2]
We observed that in the group carrying D4Z4 reduced allele (DRA) with 4–10 Repeat Units (RUs) index cases have higher ΔFSHD score than carrier relatives (p < 0.01), whereas we found no difference between index cases and carrier relatives carrying DRA with 1–3 RU (p = 0.831)
We investigated the possible relationships between size of DRA, or clinical phenotype, described as clinical category, with disease progression considering age, sex, length of follow-up, and facioscapulohumeral muscular dystrophy (FSHD) score at baseline

Summary

Introduction

Facioscapulohumeral muscular dystrophy (FSHD, OMIM # 158900) is a hereditary myopathy with prevalence of 1 in 8500–20,000 individuals [1, 2]. FSHD2, which represents 5–10% of cases, is contraction-independent, with affected individuals carrying two D4Z4 arrays in the healthy range (> 10 RUs) [6]. We split the analysis between index cases and carrier relatives and we classified all patients using the Comprehensive Clinical Evaluation Form (CCEF). The disease progression was measured as a variation of the FSHD score performed at baseline and at the end of 5-year follow-up (ΔFSHD score). Conclusions The progression of disease is different between index cases and carrier relatives and the assessment of the CCEF categories has strong prognostic effect in FSHD1 patients

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Conclusion