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.
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B.C. is a senior clinical investigator funded by Fund for Scientific Research Flanders (FWO). This project was funded by the Special Research foundation of Ghent University to B.C. (starting grant BOFSTA2016002401) and to A.D.P. (Methusalem grant BOF15/MET-V/011). We thank Jan C. Oosterwijk and Rebecca Igbokwe for their helpful comments on the manuscript. We are grateful to all patients and their families for their interest and participation.
The authors declare no conflicts of interest.
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Meerschaut, I., De Coninck, S., Steyaert, W. et al. A clinical scoring system for congenital contractural arachnodactyly. Genet Med (2019) doi:10.1038/s41436-019-0609-8
- congenital contractural arachnodactyly
- Beals syndrome
- clinical score
- diagnostic criteria