Afhandling--Copenhagen.

Afhandling--Copenhagen.

Heterotaxy refers to the abnormal arrangement of internal organs in relation to each other. Model organism studies have shown that functions of more than eighty genes are required for normal asymmetric left-right organ development. CRELD1 has been shown to be necessary for proper heart development and mutations in CRELD1 are known to increase risk of cardiac atrioventricular septal defects (AVSD). AVSD is the most common form of heart defect associated with heterotaxy, and we have previously shown that some individuals with heterotaxy-related AVSD have mutations in CRELD1. Therefore, we propose to examine the CRELD1 gene in a large sample of patients with heterotaxy syndrome. Our goal was to determine if mutations in CRELD1 are associated with other manifestations of heterotaxy or if they only coincide with AVSD. To achieve this aim, a sample size of 126 patients with heterotaxy collected by Dr. Belmont, Baylor college of Medicine, Texas, with approximately 66% of the heterotaxy population with different types of heart defects, were used for this study. Ten exons, promoter regions, and regulatory elements in the introns of CRELD1 gene were sequenced and analyzed. In this study three different heterozygous missense mutations in CRELD1 were identified in three unrelated individuals. These three individuals were diagnosed with different forms of heart defects in addition to AVSD. All three mutations were identified in highly conserved regions of CRELD1 possibly altering the CRELD1 properties. This demonstrates that mutations in CRELD1 may increase the susceptibility of AVSD in heterotaxy population. This information can help us to find factors effecting disease susceptibility in heterotaxy patients since the heart defects are a complex trait with incomplete penetrance.

Made available in DSpace on 2016-01-26T12:51:45Z (GMT). No. of bitstreams: 1 carlosdemarchi_tese.pdf: 849020 bytes, checksum: f72fc171abbb042bef869d955b6fd632 (MD5) Previous issue date: 2004-09-10 / Objective: Balloon atrial septostomy (BAS) is a life-saving palliative procedure for some congenital heart defects and typically performed in the cardiac catheterization laboratory. The aim of this study was to evaluate BAS under echocardiographic guidance. Method: From August 1997 through January 2004, 31 children with congenital heart defects with indication of ASB were submitted to the procedure under exclusive echocardiographic guidance. Success was admitted the obtaining of atrial septal defect (ASD) with size of four millimeters (mm) or greater and torn septal tissue flapping freely. Results: Male infants predominated (83.9%). Median age was 5 days (1 - 150) and median weight was 3300g (1800 - 7500). Transposition of the Great Arteries was present in 80.6%, Tricuspid Atresia in 12.9%, Total Anomalous Pulmonary Venous Return in 3.2% and Pulmonary Atresia with intact ventricular septum in 3.2%. The procedure was successful in all cases. ASD size increased from 1.8 ± 0.8 mm to 5.8 ± 1.3 mm (P<0.0001) and arterial oxygen saturation increased from 64.5 ± 18.9% to 85.1 ± 9.2% (P<0.0001). As complications occured three balloon ruptures, one tear of right femoral vein, one case of supraventricular tachycardia and one case of atrial flutter. Conclusion: BAS under echocardiographic guidance is a safe and effective method. It can be performed at the bedside, identifies the catheter location avoiding serious complications and evaluates the immediate result of the procedure. / Atnosseptostomia com balão (ASB) é procedimento de grande valor no tratamento de cardiopatias congênitas e monitorado tradicionalmente por radioscopia. O objetivo do presente estudo foi avaliar a ASB monitorada pela ecocardiografia. Casuística e Método: Entre agosto de 1997 e janeiro de 2004, 31 crianças foram submetidas à ASB sob monitoração ecocardiográfica exclusiva. Admitiu-se sucesso a obtenção de comunicação interatrial (CIA) com diâmetro igual ou maior que quatro milímetros (mm) e com ampla mobilidade das suas margens. Dados coletados: diâmetro da CIA e saturação arterial de oxigênio (SAT) iniciais e finais e número de trações do cateter balão. Resultados: Sexo masculino predominou (83,9%). A idade mediana foi de 5 dias (1-150) e o peso teve mediana de 3300g (1800-7500). Transposição das Grandes Artérias ocorreu em 80,6%, Atresia Tricúspide em 12,9%, Drenagem Anômala Total de Veias Pulmonares em 3,2% e Atresia Pulmonar com septo Integro em 3,2%. Sucesso foi obtido em todos os casos. O tamanho da CIA aumentou de 1,8 0,8 mm para 5,8 1,3 mm (p <0,0001) e a SAT aumentou de 64,5 18,9 % para 85,1 9,2 % (p < 0,0001). Complicações ocorridas: três rupturas de balão, uma lesão de veia femoral direita, uma taquicardia supraventricular e um flutter atnal. Conclusões: ASB monitorada pela ecocardiografia é método seguro e eficaz. Possibilita a realização do procedimento à beira do leito evitando o transporte da criança, identifica o posicionamento do cateter reduzindo complicações graves e avalia o resultado imediato do procedimento.