Spontaneous coronary artery dissection and heritable connective tissue disease
Paediatrics and Child Health
Background: Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic cause of acute coronary syndrome with a predilection for young women. Genetic risk factors for SCAD are not well characterized.
Methods: We performed a retrospective single-center descriptive analysis of consecutive patients with SCAD (n=114) who had undergone comprehensive genetic evaluation. The presence or absence of six features suggestive of heritable connective tissue disease (CTD) were extracted: facial features, myopia, skin features, pectus deformity, arachnodactyly, and joint hypermobility. Physical examination features were stratified as mildly (0-2 features), moderately (3-4 features), or strongly (5-6 features) suggestive of a heritable disorder. Genetic testing, if performed, was also reviewed.
Results: Of the 114 patients (mean age 44.1 years, 94.7% women), 49 (43.0%) had fibromuscular dysplasia (FMD), and six (5.3%) had features moderately suggestive of a heritable CTD. No patients had features strongly suggestive of a heritable disorder. Four of 6 patients underwent genetic testing, which was normal. Of the 58 total patients who underwent genetic testing (panel-based sequencing of genes associated with arterial dissection), only 2 (3.4%) received a diagnosis of CTD as a result of clinical features and a definite mutation: a 50 year-old man with Marfan's Syndrome (FBN1) who had a dissection of distal left anterior descending artery; and 43 year-old woman with Type IV Ehlers-Danlos Syndrome and FMD who had dissection of left anterior descending and ramus arteries. Neither of the two patients had any identifiable family history of CTD or vascular dissections or aneurysms. An additional 11 patients (19.0%) had variants of unknown significance, none of which was thought to be a definite disease causing mutation based on in-silico analyses.
Conclusion: Only a minority of patients with SCAD who undergo genetic evaluation have a likely pathogenic mutation identified on gene panel testing. Even fewer exhibit clinical features of CTD. These findings underscore the need for further studies to elucidate mechanisms of SCAD.
Publication ( Name of Journal)
Journal of the American College of Cardiology
(2015). Spontaneous coronary artery dissection and heritable connective tissue disease. Journal of the American College of Cardiology, 65(10_Supplement), A7-A7.
Available at: https://ecommons.aku.edu/pakistan_fhs_mc_women_childhealth_paediatr/1290