Double Trouble: a Comprehensive Study into Unrelated Genetic Comorbidities in Adult Patients with Facioscapulohumeral Muscular Dystrophy Type I

Overview

Journal Eur J Hum Genet

Specialty Genetics

Date 2025 Jan 8

PMID 39775061

Authors

Angela Puma

Giulia Tammam

Andra Ezaru

Abderhmane Slioui

Eleonora Torchia

Giorgio Tasca

Luisa Villa

Michele Cavalli

Leonardo Salviati

Patrick J van der Vliet

Richard Jlf Lemmers

Jonathan Pini

Silvere M van der Maarel

Sabrina Sacconi

Affiliations

Soon will be listed here.

Abstract

Facioscapulohumeral dystrophy type 1 (FSHD1) displays prominent intra- and interfamilial variability, which complicates the phenotype-genotype correlation. In this retrospective study, we investigated FSHD1 patients classified as category D according to the Comprehensive Clinical Evaluation Form (CCEF), a category defined by FSHD patients showing uncommon clinical features, to identify genetic causes explaining these uncommon phenotypes. Demographics, clinical data and clinical scales of FSHD1 patients were retrospectively evaluated. Patients were divided into four CCEF categories, and comparisons between groups were performed. In category D, when uncommon features suggested the presence of an unrelated genetic disease, a more extensive collection of data was performed. 157 FSHD1 patients were included in the study (82 males, 75 females) with mean age of 52.1 ± 13.5 years at the time of the study. D4Z4 repeat sizes ranged between 2 and 10 RU. According to the CCEF, 114 patients were classified into category A, 8 into category B and C each, and 27 into category D. In category D, 9 patients presented uncommon features related to commonly acquired comorbidities, whereas in the remaining 18 patients, all but two with upper-sized FSHD1 D4Z4 repeats (7-10 RU), we suspected an unrelated genetic neurological disease based on clinical phenotype. In 14/18 patients, we identified FSHD-unrelated genetic causes, most often unrelated repeat expansion disorders. This emphasizes the need of careful clinical and genetic work-up to avoid confusion between FSHD-intrinsic clinical variability and clinical features unrelated to the disease.

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