A family with Classical Ehlers-Danlos Syndrome (cEDS), mild bone fragility and without vascular complications, caused by the p.Arg312Cys mutation in COL1A1

Abstract

The Ehlers-Danlos syndromes (EDS) are heritable disorders of connective tissue (HDCT) with joint hypermobility, skin hyperextensibility and tissue fragility, which were recently re-classified (2017 International Classification). Most patients (>90%) with Classical Ehlers-Danlos syndrome (cEDS) have a mutation in the COL5A1 or COL5A2 genes encoding type V procollagen. A small number of patients with the p.Arg312Cys mutation in COL1A1 have been reported with overlapping features of both cEDS and vascular EDS (vEDS). In this report, we describe two patients from a large family with this mutation and clinical features consistent with cEDS without vascular complications. The proband presented with congenital hip dislocation (previously reported in one patient), the mother of the proband with multiple fractures in childhood, and dental defects (novel findings). The small number of patients reported with this mutation and proportion with vascular complications suggests that vascular surveillance should still be recommended.