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Journal Articles Neurology Year : 2019

FSHD1 and FSHD2 form a disease continuum

Angela Puma
Tanya Stojkovic
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  • PersonId : 956119
Christophe Vial
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  • PersonId : 759701
  • IdRef : 175476071
Françoise Bouhour
  • Function : Author
  • PersonId : 895072
Gael Cristofari


Objective: To compare the clinical features of patients showing a classical phenotype of facioscapulohumeral muscular dystrophy (FSHD) with genetic and epigenetic characteristics of the FSHD1 and FSHD2 loci D4Z4 and SMCHD1. Methods: This is a national multicenter cohort study. We measured motor strength, motor function, and disease severity by manual muscle testing sumscore, Brooke and Vignos scores, clinical severity score (CSS), and age-corrected CSS, respectively. We correlated these scores with genetic (D4Z4 repeat size and haplotype; SMCHD1 variant status) and epigenetic (D4Z4 methylation) parameters. Results: We included 103 patients: 54 men and 49 women. Among them, we identified 64 patients with FSHD1 and 20 patients with FSHD2. Seven patients had genetic and epigenetic characteristics of FSHD1 and FSHD2, all carrying repeats of 9–10 D4Z4 repeat units (RU) and a pathogenic SMCHD1 variant. In the remaining patients, FSHD was genetically excluded or remained unconfirmed. All clinically affected SMCHD1 mutation carriers had a D4Z4 repeat of 9–16 RU on a disease permissive 4qA haplotype. These patients are significantly more severely affected by all clinical scales when compared to patients with FSHD1 with upper-sized FSHD1 alleles (8–10 RU). Conclusion: The overlap between FSHD1 and FSHD2 patients in the 9–10 D4Z4 RU range suggests that FSHD1 and FSHD2 form a disease continuum. The previously established repeat size threshold for FSHD1 (1–10 RU) and FSHD2 (11–20 RU) needs to be reconsidered.

Dates and versions

hal-02305410 , version 1 (04-10-2019)



Sabrina Sacconi, Audrey Briand-Suleau, Marilyn Gros, Christian Baudoin, Richard J.L.F. Lemmers, et al.. FSHD1 and FSHD2 form a disease continuum. Neurology, 2019, 92 (19), pp.e2273-e2285. ⟨10.1212/WNL.0000000000007456⟩. ⟨hal-02305410⟩
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