Background: We recently reported the first risk allele for SCAD, a variant (rs9349379-A) in the PHACTR1/EDN1 genetic locus (Adlam et al J Amer Coll Cardiol 73:58-66, 2019). Purpose: We sought to determine the clinical characteristics and initial genetic data for 11 families, in which more than one member has had an episode of SCAD. Methods: Participants were recruited via social media. Informed consent was obtained for whole genome sequencing and collection of clinical information. SCAD was confirmed by review of coronary angiograms and clinical data collected by phone interview and review of specialist letters. Results: Of 235 participants recruited to date, 23 cases showed familial clustering involving sister-sister pairs in six families, three first-degree cousins in one family (picture), two first-degree cousins in two families, a mother-son pair, and a family with concordant monozygotic twins, that is both twins having had SCAD. In an additional family, SCAD is discordant in monozygotic twins. A comparison of symptoms, age at SCAD, clinical syndrome, cardiovascular risk factors, SCAD risk factors, environmental triggers, SCAD location, acute management, left ventricular function and recurrent SCAD events in these families versus isolated cases, will be presented. Three sister-sister pairs have undergone whole genome sequencing and these data sets are undergoing segregation analysis to identify rare variants that are present exclusively in affected family members. Conclusions: To our knowledge, this is the largest assembly of SCAD cases with familial clustering reported to date. It provides strong evidence supporting an underlying genetic basis for SCAD, which most likely is a multi-genic disorder that also involves important gene-environment interactions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.