Thoracic aortic aneurysm in patients with loss of function Filamin A mutations: Clinical characterization, genetics, and recommendations
| Autor: | Siri Khalsa, Christopher A. Walsh, Sangita Choudhury, Ming-Hui Chen, Mami Hirata, Bernard S. Chang |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Adolescent Genotype Filamins 030204 cardiovascular system & hematology Thoracic aortic aneurysm Article Young Adult 03 medical and health sciences Aortic aneurysm 0302 clinical medicine Loss of Function Mutation medicine.artery Internal medicine Ductus arteriosus Ascending aorta Genetics Humans Medicine FLNA Genetic Predisposition to Disease Young adult Child Aortic rupture Alleles Genetic Association Studies Genetics (clinical) Aged Aortic Aneurysm Thoracic business.industry Infant Newborn Brain Infant Cardiovascular Manifestation Middle Aged medicine.disease Phenotype 030104 developmental biology medicine.anatomical_structure Echocardiography Child Preschool cardiovascular system Cardiology Female business |
| Zdroj: | Am J Med Genet A |
| ISSN: | 1552-4833 1552-4825 |
| Popis: | The frequency and gender distribution of thoracic aortic aneurysm as a cardiovascular manifestation of loss-of-function (LOF) X-linked FilaminA (FLNA) mutations are not known. 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 FLNA 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 F, 26 M, range: 0-71 years), with 75 FLNA 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% (n = 21), 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 13-41 yrs). TAA with its associated complications was also the only recorded cause of premature, non-accidental mortality in adults (2 M, 2 F). Two adult patients (1 F, 1 M, 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 FLNA mutation patients underscore the importance of serial follow-up to identify and manage these potentially devastating cardiovascular complications. |
| Databáze: | OpenAIRE |
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