Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant incurable skeletal muscle disease. FSHD1 constitutes 95% of cases and is linked to truncation of the D4Z4 macrosatellite at 4q35. In most cases the condition initially presents with facial and proximal weakness of the upper limbs, but over the course of the disease involves lower limb and truncal muscles. Weakness is progressive and frequently asymmetric, which is a hallmark of the disease. Here we performed an analysis of 643 FSHD1 patients in the UK FSHD patient registry, investigating factors affecting rate of onset of 5 major FSHD symptoms: facial, periscapular, foot dorsiflexor, hip girdle weakness, and hearing loss. We found shorter D4Z4 repeat length associated with accelerated onset of each symptom. Furthermore, paternal inheritance of the pathogenic allele was associated with accelerated onset of foot dorsiflexor weakness, while pregnancy and carrying multiple children to term was associated with slower onset of all muscle symptoms. Lastly, we performed clustering analysis on age of onset of the 4 muscle symptoms across 222 patients. We identified 4 clinical presentations of FSHD1. A classical presentation (74%) and 3 facial sparing phenotypes: a mild presentation (5%) with later facial and periscapular involvement, an early shoulder presentation (10%) with accelerated periscapular weakness and an early foot presentation (9%) with accelerated foot dorsiflexor weakness. The mild presentation was associated with longer D4Z4 repeat lengths, while the early foot presentation had a female bias. We note, however that symptom progression differs significantly in these 4 clinical presentations independently of D4Z4 repeat length and gender, motivating investigation of further modifiers of FSHD1 severity.

中文翻译：

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面肩肱型肌营养不良症 1 参加英国 FSHD 登记的患者可细分为 4 种自我报告症状模式

面肩肱型肌营养不良症 (FSHD) 是一种常染色体显性遗传的无法治愈的骨骼肌疾病。FSHD1 占病例的 95%，与 D4Z4 大卫星在 4q35 的截断有关。在大多数情况下，该病症最初表现为上肢的面部和近端无力，但在疾病过程中涉及下肢和躯干肌肉。虚弱是渐进的并且经常是不对称的，这是该疾病的标志。在这里，我们对英国 FSHD 患者登记处的 643 名 FSHD1 患者进行了分析，调查了影响 5 种主要 FSHD 症状发生率的因素：面部、肩胛骨周围、足背屈肌、髋带无力和听力损失。我们发现较短的 D4Z4 重复长度与每种症状的加速发作相关。此外，致病等位基因的父系遗传与足背屈肌无力的加速发作有关，而怀孕和生育多个孩子与所有肌肉症状的发作较慢有关。最后，我们对 222 名患者的 4 种肌肉症状的发病年龄进行了聚类分析。我们确定了 FSHD1 的 4 种临床表现。典型表现 (74%) 和 3 种面部保留表型：轻度表现 (5%) 后面部和肩胛骨受累，早期肩部表现 (10%) 加速肩胛骨周围无力，早期足部表现 (9%) 加速足背屈肌无力。温和的表现与更长的 D4Z4 重复长度相关，而早期的足表现有女性偏见。我们注意到，