Stanislav Henkin1, Sara M Negrotto1, Marysia S Tweet2, Salman Kirmani3, David R Deyle4, Rajiv Gulati2, Timothy M Olson5, Sharonne N Hayes2. 1. Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA. 2. Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA. 3. Department of Medical Genetics, Mayo Clinic, Rochester, Minnesota, USA Division of Women and Child Health, Department of Paediatrics and Child Health, The Aga Khan University, Karachi, Pakistan. 4. Department of Medical Genetics, Mayo Clinic, Rochester, Minnesota, USA. 5. Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Abstract
OBJECTIVE: Spontaneous coronary artery dissection (SCAD) is an under-recognised but important cause of myocardial infarction and sudden cardiac death. We sought to determine the role of medical and molecular genetic screening for connective tissue disorders in patients with SCAD. METHODS: We performed a single-centre retrospective descriptive analysis of patients with spontaneous coronary artery disease who had undergone medical genetics evaluation 1984-2014 (n=116). The presence or absence of traits suggestive of heritable connective tissue disease was extracted. Genetic testing for connective tissue disorders and/or aortopathies, if performed, is also reported. RESULTS: Of the 116 patients (mean age 44.2 years, 94.8% women and 41.4% with non-coronary fibromuscular dysplasia (FMD)), 59 patients underwent genetic testing, of whom 3 (5.1%) received a diagnosis of connective tissue disorder: a 50-year-old man with Marfan syndrome; a 43-year-old woman with vascular Ehlers-Danlos syndrome and FMD; and a 45-year-old woman with vascular Ehlers-Danlos syndrome. An additional 12 patients (20.3%) had variants of unknown significance, none of which was thought to be a definite disease-causing mutation based on in silico analyses. CONCLUSIONS: 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 connective tissue disorder. These findings underscore the need for further studies to elucidate the molecular mechanisms of SCAD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
OBJECTIVE: Spontaneous coronary artery dissection (SCAD) is an under-recognised but important cause of myocardial infarction and sudden cardiac death. We sought to determine the role of medical and molecular genetic screening for connective tissue disorders in patients with SCAD. METHODS: We performed a single-centre retrospective descriptive analysis of patients with spontaneous coronary artery disease who had undergone medical genetics evaluation 1984-2014 (n=116). The presence or absence of traits suggestive of heritable connective tissue disease was extracted. Genetic testing for connective tissue disorders and/or aortopathies, if performed, is also reported. RESULTS: Of the 116 patients (mean age 44.2 years, 94.8% women and 41.4% with non-coronary fibromuscular dysplasia (FMD)), 59 patients underwent genetic testing, of whom 3 (5.1%) received a diagnosis of connective tissue disorder: a 50-year-old man with Marfan syndrome; a 43-year-old woman with vascular Ehlers-Danlos syndrome and FMD; and a 45-year-old woman with vascular Ehlers-Danlos syndrome. An additional 12 patients (20.3%) had variants of unknown significance, none of which was thought to be a definite disease-causing mutation based on in silico analyses. CONCLUSIONS: 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 connective tissue disorder. These findings underscore the need for further studies to elucidate the molecular mechanisms of SCAD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Authors: Ingrid Tarr; Stephanie Hesselson; Siiri E Iismaa; Emma Rath; Steven Monger; Michael Troup; Ketan Mishra; Claire M Y Wong; Pei-Chen Hsu; Keerat Junday; David T Humphreys; David Adlam; Tom R Webb; Anna A Baranowska-Clarke; Stephen E Hamby; Keren J Carss; Nilesh J Samani; Monique Bax; Lucy McGrath-Cadell; Jason C Kovacic; Sally L Dunwoodie; Diane Fatkin; David W M Muller; Robert M Graham; Eleni Giannoulatou Journal: Circ Genom Precis Med Date: 2022-05-18
Authors: Sharonne N Hayes; Esther S H Kim; Jacqueline Saw; David Adlam; Cynthia Arslanian-Engoren; Katherine E Economy; Santhi K Ganesh; Rajiv Gulati; Mark E Lindsay; Jennifer H Mieres; Sahar Naderi; Svati Shah; David E Thaler; Marysia S Tweet; Malissa J Wood Journal: Circulation Date: 2018-02-22 Impact factor: 29.690
Authors: Christopher Traenka; Manja Kloss; Tim Strom; Philippe Lyrer; Tobias Brandt; Leo H Bonati; Caspar Grond-Ginsbach; Stefan Engelter Journal: Eur Stroke J Date: 2019-07-12