RESUMEN
BACKGROUND: Childhood-onset cardiomyopathy is a heterogeneous group of conditions the cause of which is largely unknown. The influence of consanguinity on the genetics of cardiomyopathy has not been addressed at a large scale. METHODS: To unravel the genetic cause of childhood-onset cardiomyopathy in a consanguineous population, a categorized approach was adopted. Cases with childhood-onset cardiomyopathy were consecutively recruited. Based on the likelihood of founder mutation and on the clinical diagnosis, genetic test was categorized to either (1) targeted genetic test with targeted mutation test, single-gene test, or multigene panel for Noonan syndrome, or (2) untargeted genetic test with whole-exome sequencing or whole-genome sequencing. Several bioinformatics tools were used to filter the variants. RESULTS: Two-hundred five unrelated probands with various forms of cardiomyopathy were evaluated. The median age of presentation was 10 months. In 30.2% (n=62), targeted genetic test had a yield of 82.7% compared with 33.6% for whole-exome sequencing/whole-genome sequencing (n=143) giving an overall yield of 53.7%. Strikingly, 96.4% of the variants were homozygous, 9% of which were found in 4 dominant genes. Homozygous variants were also detected in 7 novel candidates (ACACB, AASDH, CASZ1, FLII, RHBDF1, RPL3L, ULK1). CONCLUSIONS: Our work demonstrates the impact of consanguinity on the genetics of childhood-onset cardiomyopathy, the value of adopting a categorized population-sensitive genetic approach, and the opportunity of uncovering novel genes. Our data suggest that if a founder mutation is not suspected, adopting whole-exome sequencing/whole-genome sequencing as a first-line test should be considered.
Asunto(s)
Cardiomiopatías/genética , Acetil-CoA Carboxilasa/genética , Adolescente , Cardiomiopatías/diagnóstico , Niño , Preescolar , Proteínas de Unión al ADN/genética , Femenino , Pruebas Genéticas/métodos , Homocigoto , Humanos , Lactante , Recién Nacido , L-Aminoadipato-Semialdehído Deshidrogenasa/genética , Masculino , Linaje , Factores de Transcripción/genética , Secuenciación del ExomaRESUMEN
We report a case of cardiac rhabdomyomas in an infant who presented with right ventricular tachycardia, and a clinical picture of infective endocarditis. Typical features of tuberous sclerosis developed subsequently. To the best of our knowledge, cardiac rhabdomyoma has not been reported previously in association with infective endocarditis.
Asunto(s)
Endocarditis/etiología , Neoplasias Cardíacas/complicaciones , Rabdomioma/complicaciones , Taquicardia Ventricular/etiología , Esclerosis Tuberosa/complicaciones , Diagnóstico Diferencial , Neoplasias Cardíacas/diagnóstico , Humanos , Recién Nacido , Masculino , Rabdomioma/diagnóstico , Esclerosis Tuberosa/diagnósticoRESUMEN
OBJECTIVES: To estimate the incidence and timing of spontaneous closure of atrial septal defects within the oval fossa, to study the modalities for diagnosis, and predict the need for therapeutic intervention. METHODS: We reviewed retrospectively the medical records of patients with isolated atrial septal defects within the oval fossa, so-called "secundum defects", diagnosed between January 1990 and February 2003. Based on the initial echocardiographic evaluation, we divided defects into small ones measuring from 3 to 5 mm, medium ones from 5 to 8 mm, and large ones greater than 8 mm. RESULTS: We identified 121 patients, 50 (41.3%) of whom had failed to thrive, and 14 (11.6%) had congestive heart failure. At a mean of 44.9 +/- 22.1 months following diagnosis, with a range from 12 to 102 months, the defects had closed spontaneously in 31 patients (25.6%). Of 22 patients having small defects, spontaneous closure occurred in 18 (82%) at a mean age of 18.9 +/- 10.2 months. Of 27 patients with defects of medium size, 12 (44%) either experienced spontaneous closure, or else the defect effectively became a patent oval foramen, at a mean age of 51.2 +/- 32.2 months. Only 1 (1.4%) of the 72 patients with a defect larger than 8 mm in size underwent spontaneous closure. The defects increased in size in 8 patients (6.6%). Intervention was necessary in 76 patients (63%) at a mean age of 75.5 +/- 15.2 months. CONCLUSION: The initial size of a defect within the oval fossa at diagnosis is the best predictor of its natural history. Some defects increase in size with growth, irrespective of their initial size.
Asunto(s)
Defectos del Tabique Interatrial/diagnóstico , Factores de Edad , Procedimientos Quirúrgicos Cardíacos/métodos , Niño , Preescolar , Estudios de Cohortes , Ecocardiografía Doppler , Electrocardiografía/métodos , Femenino , Estudios de Seguimiento , Defectos del Tabique Interatrial/cirugía , Humanos , Lactante , Recién Nacido , Masculino , Probabilidad , Radiografía Torácica , Remisión Espontánea , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Factores de TiempoRESUMEN
We report a case of Uhl's anomaly in a 5-month-old cyanotic infant who presented with thromboembolic stroke and acute hemiparesis. The patient underwent successfully an initial surgical repair, which included exclusion of the right ventricle by patch closure of the tricuspid valve, atrial septectomy and construction of a bidirectional Glenn shunt. This was followed by successful construction of a total cavopulmonary connection.