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Furthermore, there is very limited cardiovascular morbidity or mortality data in children and adults. We analyzed cardiac data on the largest series of 114 patients with LOF <jats:italic>FLNA<\/jats:italic> mutations, both children and adults, with periventricular nodular heterotopia (PVNH), including 48 study patients and 66 literature patients, median age of 22.0 years (88\u2009F, 26\u2009M, range: 0\u201371 years), with 75 <jats:italic>FLNA<\/jats:italic> mutations observed in 80 families. Most (64.9%) subjects had a cardiac anomaly or vascular abnormality (80.8% of males and 60.2% of females). Thoracic aortic aneurysms or dilatation (TAA) were found in 18.4% (<jats:italic>n<\/jats:italic>\u2009=\u200921), and were associated with other structural cardiac malformations in 57.1% of patients, most commonly patent ductus arteriosus (PDA) and valvular abnormalities. TAA most frequently involved the aortic root and ascending aorta, and sinus of Valsalva aneurysms were present in one third of TAA patients. Six TAA patients (28.5%) required surgery (median age 37 yrs, range 13\u201341 yrs). TAA with its associated complications was also the only recorded cause of premature, non\u2010accidental mortality in adults (2\u2009M, 2\u2009F). Two adult patients (1\u2009F, 1\u2009M, median 38.5 yrs), died of spontaneous aortic rupture at aortic dimensions smaller than current recommendations for surgery for other aortopathies. Data from this largest series of LOF <jats:italic>FLNA<\/jats:italic> mutation patients underscore the importance of serial follow\u2010up to identify and manage these potentially devastating cardiovascular complications.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38580","type":"journal-article","created":{"date-parts":[[2018,1,16]],"date-time":"2018-01-16T12:37:31Z","timestamp":1516106251000},"page":"337-350","source":"Crossref","is-referenced-by-count":67,"title":["Thoracic aortic aneurysm in patients with loss of function <i>Filamin A<\/i> mutations: Clinical characterization, genetics, and recommendations"],"prefix":"10.1002","volume":"176","author":[{"given":"Ming Hui","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Cardiology Boston Children's Hospital Boston Massachusetts"},{"name":"Division of Genetics and Genomics Manton Center for Orphan Disease Research, Department of Pediatrics and Howard Hughes Medical Institute Boston Children's Hospital Boston Massachusetts"},{"name":"Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangita","family":"Choudhury","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Manton Center for Orphan Disease Research, Department of Pediatrics and Howard Hughes Medical Institute Boston Children's Hospital Boston Massachusetts"},{"name":"Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mami","family":"Hirata","sequence":"additional","affiliation":[{"name":"Tokyo Women's Medical University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siri","family":"Khalsa","sequence":"additional","affiliation":[{"name":"Department of Cardiology Boston Children's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Chang","sequence":"additional","affiliation":[{"name":"Harvard Medical School Boston Massachusetts"},{"name":"Department of Neurology Beth Israel Deaconess Medical Center Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0156-2238","authenticated-orcid":false,"given":"Christopher A.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Manton Center for Orphan Disease Research, Department of Pediatrics and Howard Hughes Medical Institute Boston Children's Hospital Boston Massachusetts"},{"name":"Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,15]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"GeneReviews(R)","author":"Chen M. 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