RESUMO
INTRODUCTION: To investigate cardiovascular characteristics and progressions of hypertrophic cardiomyopathy (HCM) and pulmonary stenosis (PS) and determine whether any genotype-phenotype correlations exist in patients with gene-confirmed RASopathy syndrome. STUDY DESIGN: Eighty patients (male, 55%) confirmed as having RASopathy syndrome by genetic testing at a single tertiary center were enrolled. Subjects' medical and echocardiography records were reviewed and the changes in the z scores of left ventricular wall thickness (LVWT) and the degree of PS over time were examined during follow-up of 5.7 ± 3.1 and 7.5 ± 5.2 years, respectively. RESULTS: The most common RASopathy gene identified was PTPN11 (56%), followed by RAF1 (10%). Eighty-five percent of patients had cardiovascular diseases, wherein 42% had HCM, and 38% PS. Mean maximal LVWT z score on the initial echocardiography (mean age 5.0 ± 6.0 years) was 3.4 ± 1.3 (median 2.8, range 2.1-6.6) in the HCM group. Overall, the maximal LVWT increased with time, especially in the HCM group (z = 3.4 ± 1.3 to 3.7 ± 1.6, P = .008) and RAF1-variant group (z = 3.7 ± 1.7 to 4.6 ± 1.8, P = .031). Five patients newly developed HCM during the study period. Genotype-phenotype correlation was significant for HCM (P = .002); 31% of patients with PTPN11 and 88% with RAF1 variants had HCM. PS did not progress in this study cohort. CONCLUSIONS: In this study, progression of ventricular hypertrophy was seen in a significant number of patients with genotype correlation. Thus, long-term follow up of cardiovascular problems in patients with RASopathy is necessary.
Assuntos
Cardiomiopatia Hipertrófica , Estenose da Valva Pulmonar , Humanos , Masculino , Pré-Escolar , Criança , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/genética , Testes Genéticos , Genótipo , Genômica , Estenose da Valva Pulmonar/complicações , Estenose da Valva Pulmonar/genéticaRESUMO
OBJECTIVE: To quantify outcomes of infants (<1 year of age) diagnosed with pulmonary vein stenosis (PVS). STUDY DESIGN: MEDLINE (PubMed), Scopus, and Web of Science were searched through February 1, 2017, with no language restrictions. Publications including infants diagnosed with primary PVS, defined as the absence of preceding intervention(s), were considered. The study was performed according to Meta-analysis of Observational Studies in Epidemiology guidelines, the Systematic Reviews, and Meta-Analysis checklist, and registered prospectively. The quality of selected reports was critically examined. Data extraction was independently performed by multiple observers with outcomes agreed upon a priori. Data were pooled using an inverse variance heterogeneity model with incidence of mortality the primary outcome of interest. RESULTS: Forty-eight studies of 185 infants were included. Studies were highly diverse with regards to the participants, interventions, and outcomes reported. The median (range) age at diagnosis was 5.0 (0.1-11.6) months. Pooled mortality was 58.5% (95% CI 49.8%-67.0%, I2 = 21.4%). We observed greater mortality incidence among infants with 3 or 4 vein stenoses than in those with 1 or 2 vein stenoses (83.3% vs 36.1%; P < .01). We observed greater mortality among infants with bilateral than unilateral disease (78.7% vs 26.0%; P < .01). CONCLUSIONS: Studies of primary PVS during infancy are highly variable in their methodological quality and estimates of clinical outcomes; therefore, estimates of prognosis remain uncertain. Multicenter, interdisciplinary collaborations, including alignment of key outcome measurements, are needed to answer questions beyond the scope of available data.