Puma Angela, Tammam Giulia, Ezaru Andra, Slioui Abderhmane, Torchia Eleonora, Tasca Giorgio, Villa Luisa, Cavalli Michele, Salviati Leonardo, van der Vliet Patrick J, Lemmers Richard Jlf, Pini Jonathan, van der Maarel Silvère M, Sacconi Sabrina
Peripheral Nervous System & Muscle Department, Pasteur 2 Hospital, Nice University Hospital, Nice, France.
Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Eur J Hum Genet. 2025 Jan 7. doi: 10.1038/s41431-024-01770-0.
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.
1型面肩肱型肌营养不良症（FSHD1）表现出显著的家族内和家族间变异性，这使得表型-基因型相关性变得复杂。在这项回顾性研究中，我们调查了根据综合临床评估表（CCEF）被归类为D类的FSHD1患者，该类别由具有不常见临床特征的FSHD患者定义，以确定解释这些不常见表型的遗传原因。对FSHD1患者的人口统计学、临床数据和临床量表进行了回顾性评估。患者被分为四个CCEF类别，并进行了组间比较。在D类中，当不常见特征提示存在无关的遗传疾病时，会进行更广泛的数据收集。本研究纳入了157例FSHD1患者（82例男性，75例女性），研究时的平均年龄为52.1±13.5岁。D4Z4重复序列大小在2至10个重复单位（RU）之间。根据CCEF，114例患者被归类为A类，8例为B类，8例为C类，27例为D类。在D类中，9例患者表现出与常见获得性合并症相关的不常见特征，而在其余18例患者中，除了两名具有较大FSHD1 D4Z4重复序列（7 - 10 RU）的患者外，基于临床表型，我们怀疑存在无关的遗传性神经疾病。在18例患者中的14例中，我们确定了与FSHD无关的遗传原因，最常见的是无关的重复序列扩增疾病。这强调了需要进行仔细的临床和基因检查，以避免FSHD内在临床变异性与与疾病无关的临床特征之间的混淆。
