A clinical scoring system for congenital contractural arachnodactyly.

Genet Med 2020 01 18;22(1):124-131. Epub 2019 Jul 18.

Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: Our clinical score is helpful for clinical guidance for patients suspected to have CCA, and provides a quantitative tool for phenotyping in research settings.

Download full-text PDF

Source
http://www.nature.com/articles/s41436-019-0609-8
Publisher Site
http://dx.doi.org/10.1038/s41436-019-0609-8DOI Listing
January 2020
12 Reads

Publication Analysis

Top Keywords

scoring system
12
clinical scoring
12
congenital contractural
8
contractural arachnodactyly
8
clinical
6
support diagnostic
4
diagnostic process
4
criteria support
4
diagnostic criteria
4
system diagnostic
4
process guide
4
guide molecular
4
retrospective study
4
study assessed
4
testingmethods retrospective
4
genetic testingmethods
4
molecular genetic
4
designed clinical
4
suggested designed
4
challenging prognosis
4

References

(Supplied by CrossRef)

F Hecht et al.
Pediatrics 1972

MA Ramos Arroyo et al.
Clin Genet 1985

D Viljoen et al.
J Med Genet 1994

PA Gupta et al.
Hum Mutat 2002

BL Callewaert et al.
Hum Mutat 2009

M Bamshad et al.
Am J Med Genet 1996

AJ Macnab et al.
Arch Dis Child 1991

PA Gupta et al.
J Med Genet 2004

N Takeda et al.
Am J Med Genet A 2015

RA Anderson et al.
Am J Med Genet 1984

RE Bell et al.
South Med J 1985

Similar Publications