RESUMO
Sudden cardiac death, mostly related to ventricular arrhythmia, is a major public health issue, with still very poor survival at hospital discharge. Although coronary artery disease remains the leading cause, other etiologies should be systematically investigated. Exhaustive and standardized exploration is required to eventually offer specific therapeutics and management to the patient as well as his/her family members in case of inherited cardiac disease. Identification and establishing direct causality of the detected cardiac anomaly may remain challenging, underlying the need for a multidisciplinary and experimented team.
Assuntos
Morte Súbita Cardíaca/etiologia , Adulto , Fatores Etários , Algoritmos , Arritmias Cardíacas/complicações , Arritmias Cardíacas/diagnóstico , Autopsia , Cardiomiopatias/complicações , Doença da Artéria Coronariana/complicações , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/prevenção & controle , Feminino , França/epidemiologia , Doenças Genéticas Inatas/complicações , Doenças Genéticas Inatas/diagnóstico , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Sistema de Registros , Fatores de Risco , Fatores SexuaisRESUMO
Syndromic thoracic aortic aneurysm and dissection (TAAD) can suggest Marfan, vascular Ehlers-Danlos or Loeys-Dietz (LDS) syndromes. Several of the TGFß-pathway-related genes predispose to different types of LDS. Heterozygous loss-of-function variations in TGFß2 have been shown to be responsible for a novel form of syndromic TAAD associated with an impairment of the mitral valve and cerebrovascular disease called Loeys-Dietz syndrome type 4 (LDS4). We report the clinical characterization of a LDS4 French family with sudden deaths and diffuse vascular lesions, caused by a frameshift mutation in TGFß2 gene: c.[995del]; p.(Leu332TrpfsTer27). Clinical characteristics include aneurysm of aortic sinus, skeletal and cutaneous features compatible with a syndromic form of TAAD (joint hypermobility, scoliosis, and easy bruises), intracranial aneurysms and rare mitral valve involvement. Iliac aneurysms, systemic medium caliber arteries dissections, and mild developmental delay were present in the family, and have not been described in LDS4. Phenotypic variability was also an important finding, including absence of clinical vascular events at advanced age in one case. Our data expand the phenotype of LDS4: we confirm that TGFß2 mutations are responsible for true LDS syndrome with non-specific features of connective tissue disorders and diffuse vascular lesions. Adapted vascular follow up and prevention has to be proposed for these patients.
