A diagnosis of vascular ehlers-danlos syndrome in childhood: clinical and molecular features of 63 individuals

Abstract Background Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder characterised by generalised severe tissue friability and predominantly caused by pathogenic COL3A1 variants. Diagnosis of vEDS in childhood primarily occurs due to a positive family history and/or the occurrence of an early arterial or intestinal event. However, little has been reported on additional clinical characteristics and management in this population. Purpose This study aims to identify critical drivers of a childhood vEDS diagnosis in individuals diagnosed through a national EDS service. Methods 63 individuals (24 index, 31 females) with a clinical and genetic diagnosis of vEDS in childhood (< 18 years) were identified through a national EDS service, and childhood cardiovascular surveillance was conducted through joint inherited cardiovascular disease clinics. Results Diagnosis of vEDS in childhood occurred at a median age of 7 years (IQR 3-12) and was predominantly driven by positive family history of vEDS (55.5%). Clinical investigations were directly initiated by occurrence of a major clinical event in n=13 (20.6%), and a total of 17 major clinical events in childhood were recorded in 13 individuals. First events occurred at a median age of 11 years (IQR 0-13) and vascular events, though infrequent, occurred as early as the first year of life. In individuals who did not have a positive family history or major event, easy and/or excessive bruising was the most frequent cause for referral (60%). Conclusions This cohort provides further details of the clinical and genetic characteristics of children with vEDS and contributes new insight into drivers of vEDS diagnosis in childhood and the importance of long-term management, including paediatric cardiovascular surveillance.