RESUMEN
BACKGROUND: Few clinical data are available on NEXN mutation carriers, and the gene's involvement in cardiomyopathies or sudden death has not been fully established. Our objectives were to assess the prevalence of putative pathogenic variants in NEXN and to describe the phenotype and prognosis of patients carrying the variants. METHODS: DNA samples from consecutive patients with cardiomyopathy or sudden cardiac death/sudden infant death syndrome/idiopathic ventricular fibrillation were sequenced with a custom panel of genes. Index cases carrying at least one putative pathogenic variant in the NEXN gene were selected. RESULTS: Of the 9516 index patients sequenced, 31 were carriers of a putative pathogenic variant in NEXN only, including 2 with double variants and 29 with a single variant. Of the 29 unrelated probands with a single variant (16 males; median age at diagnosis, 32.0 [26.0-49.0] years), 21 presented with dilated cardiomyopathy (prevalence, 0.33%), and 3 presented with hypertrophic cardiomyopathy (prevalence, 0.14%). Three patients had idiopathic ventricular fibrillation, and there were 2 cases of sudden infant death syndrome (prevalence, 0.46%). For patients with dilated cardiomyopathy, the median left ventricle ejection fraction was 37.5% (26.25-50.0) at diagnosis and improved with treatment in 13 (61.9%). Over a median follow-up period of 6.0 years, we recorded 3 severe arrhythmic events and 2 severe hemodynamic events. CONCLUSIONS: Putative pathogenic NEXN variants were mainly associated with dilated cardiomyopathy; in these individuals, the prognosis appeared to be relatively good. However, severe and early onset phenotypes were also observed-especially in patients with double NEXN variants. We also detected NEXN variants in patients with hypertrophic cardiomyopathy and sudden infant death syndrome/idiopathic ventricular fibrillation, although a causal link could not be established.
Asunto(s)
Cardiomiopatías , Cardiomiopatía Dilatada , Cardiomiopatía Hipertrófica , Muerte Súbita del Lactante , Fibrilación Ventricular , Masculino , Lactante , Humanos , Adulto , Persona de Mediana Edad , Cardiomiopatía Dilatada/genética , Prevalencia , Cardiomiopatías/diagnóstico , Fenotipo , Cardiomiopatía Hipertrófica/genética , Cardiomiopatía Hipertrófica/complicaciones , Muerte Súbita Cardíaca/etiología , Pronóstico , Proteínas de Microfilamentos/genéticaRESUMEN
Tako-tsubo cardiomyopathy is characterized by a total reversibility of wall motion abnormalities of the left ventricle (LV) as well as normalization of LV ejection fraction after the acute phase. However, recent studies have shown that some patients present functional, metabolic, and morphologic abnormalities away from the acute phase suggesting an incomplete recovery of the disease. In this revue we discuss about this topic through several tools used in those studies (echocardiography, exercise test, MRI, nuclear imaging, biology, as well).
