Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Department of Pediatrics, Ghent University Hospital, Ghent, Belgium.
Genet Med. 2020 Jan;22(1):124-131. doi: 10.1038/s41436-019-0609-8. Epub 2019 Jul 18.
Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder manifesting joint contractures, arachnodactyly, crumpled ears, and kyphoscoliosis as main features. Due to its rarity, rather aspecific clinical presentation, and overlap with other conditions including Marfan syndrome, the diagnosis is challenging, but important for prognosis and clinical management. CCA is caused by pathogenic variants in FBN2, encoding fibrillin-2, but locus heterogeneity has been suggested. We designed a clinical scoring system and diagnostic criteria to support the diagnostic process and guide molecular genetic testing.
In this retrospective study, we assessed 167 probands referred for FBN2 analysis and classified them into a FBN2-positive (n = 44) and FBN2-negative group (n = 123) following molecular analysis. We developed a 20-point weighted clinical scoring system based on the prevalence of ten main clinical characteristics of CCA in both groups.
The total score was significantly different between the groups (P < 0.001) and was indicative for classifying patients into unlikely CCA (total score <7) and likely CCA (total score ≥7) groups.
Our clinical score is helpful for clinical guidance for patients suspected to have CCA, and provides a quantitative tool for phenotyping in research settings.
先天性挛缩性蜘蛛指（趾）畸形（CCA）是一种常染色体显性结缔组织疾病，其主要特征为关节挛缩、蜘蛛指（趾）、卷曲耳和脊柱侧凸。由于其罕见性、非特异性临床表现以及与马凡综合征等其他疾病的重叠，诊断具有挑战性，但对于预后和临床管理非常重要。CCA 是由编码原纤维蛋白-2 的 FBN2 中的致病性变异引起的，但已有研究提示存在基因座异质性。我们设计了一种临床评分系统和诊断标准，以支持诊断过程并指导分子遗传学检测。
在这项回顾性研究中，我们评估了 167 名因 FBN2 分析而转诊的先证者，并根据分子分析将他们分为 FBN2 阳性（n=44）和 FBN2 阴性组（n=123）。我们基于两组中 10 种主要 CCA 临床特征的患病率，制定了一个 20 分加权临床评分系统。
两组之间的总评分差异显著（P<0.001），且可用于将患者分类为不太可能 CCA（总分<7）和可能 CCA（总分≥7）。
我们的临床评分有助于对疑似患有 CCA 的患者进行临床指导，并为研究环境中的表型提供了一种定量工具。
