Titel: Diagnosis of congenital contractural arachnodactyly (CCA) in a 12-year-old boy by clinical score and a novel de novo missense variant in FBN2
ID: P-ClinG-070
Art: Postertalk
Redezeit: 2 min
Session: Poster Session
ClinG 2

Referent: Martin Kehrer (Tübingen/DE)

Abstract - Text


Heterozygous pathogenic variants in FBN2 (fibrillin 2) are associated with congenital contractural arachnodactyly (CCA), which is a rare autosomal dominant connective tissue disorder comprising a very broad phenotypic spectrum. Accurate diagnosis is important for clinical management and prognosis, but difficult due to the rarity of the disease and often non-specific clinical presentation. To facilitate clinical diagnosis of CCA, a quantitative tool for phenotyping called "clinical scoring system for CCA" has recently been developed by Meerschaut et al. (2020). We report on a 12-year-old boy with severe progressive kyphoscoliosis. Initial clinical course and muscle biopsy suggested a nemaline myopathy. Previously performed genetic diagnostics, in particular myopathy NGS panels, had not shown any pathogenic variants. Trio exome sequencing revealed a novel heterozygous de novo missense variant (c.3212A>G, p.Tyr1071Cys) in exon 24 of FBN2. It was initially classified as variant of unknown clinical significance (class 3). By CCA-specific phenotyping of the boy by use of the clinical scoring system, he was categorized as a highly likely CCA patient. Clinical re-evaluation finally led to re-classification of the missense variant as likely pathogenic (class 4). We present detailed phenotype information of the patient and the clinical CCA score. We review the literature and compare his clinical features with those of other CCA patients.