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A phenotype of an individual is resulted from an interaction among variants in several genes. Advanced molecular technologies allow us to identify more patients with mutations in more than one genes. Here, we studied a Thai woman with combined clinical features of Marfan (MFS) and Beals (BS) syndromes including frontal bossing, enophthalmos, myopia, the crumpled appearance to the top of the pinnae, midface hypoplasia, high arched palate, dermal stretch marks, aortic enlargement, mitral valve prolapse and regurgitation, aortic root dilatation, and progressive scoliosis. The aortic root enlargement was progressive to a diameter of 7.2 cm requiring an aortic root replacement at the age of 8 years. At her last visit when she was 19 years old, she had moderate aortic regurgitation. Exome sequencing revealed that she carried the c.3159C > G (p.Cys1053Trp) in exon 26 of FBN1 and c.2638G > A (p. Gly880Ser) in exon 20 of FBN2. The variant in FBN1 was de novo, while that in FBN2 was inherited from her unaffected mother. Both genes encode for fibrillins, which are essential for elastic fibers and can form the heterotypic microfibrils. Two defective fibrillins may synergistically worsen cardiovascular manifestations seen in our patient. In this study, we identified the fourth patient with both MFS and BS, carrying mutations in both FBN1 and FBN2.

ObjectiveWe sought to characterize morphology and to evaluate a strategy of using biventricular repair in patients with a small right ventricle and an unbalanced atrioventricular septal defect.MethodsThirty-eight children with a small right ventricle and an atrioventricular septal defect underwent operative therapy. Thirty-two had biventricular repair, and 6 had single-ventricle palliation. A small right ventricle was defined on the basis of echocardiographic measurements expressed as the atrioventricular valve index (ie, right atrioventricular valve/left atrioventricular valve area) and as the ratio of right ventricular to left ventricular length. Validation of measurements in patients with a small right ventricle and an atrioventricular septal defect was achieved by comparison with balanced case-matched control subjects with atrioventricular septal defects.ResultsChildren with a small right ventricle and an atrioventricular septal defect had a lower atrioventricular valve index (mean, 0.41 ± 0.1 vs 0.52 ± 0.1 [control], P < .0001) and lower right ventricular/left ventricular length ratio (0.78 ± 0.1 vs 0.99 ± 0.17 [control], P < .0001). Children with a small right ventricle undergoing single-ventricle palliation had the smallest right ventricular dimensions. There were 4 operative deaths. Three patients with a small right ventricle and an atrioventricular septal defect who underwent biventricular repair and had an atrioventricular valve index of less than 0.50 required early reoperation for right ventricular inadequacy. A restrictive atrial fenestration was created in 11 infants. Survival at 10 years was 87% for patients undergoing biventricular repair versus 100% for control subjects (P = .042).ConclusionsExtending the use of biventricular repair in properly selected patients with a small right ventricle and an atrioventricular septal defect is feasible. An atrial fenestration improves the physiologic tolerance to repair in selected patients. The use of biventricular repair in children with atrioventricular valve indexes of less than 0.50 requires caution.

Background Whereas indications expand and results improve with increasing refinements to the Fontan procedure the overall impact on outcomes related to tricuspid atresia remains suboptimally defined. Methods We reviewed 225 consecutive patients presenting between 1971 and 1999. All patients had classic tricuspid atresia with absent right atrioventricular connection and with D-transposition of the great arteries in 21%, pulmonary outflow obstruction in 75%, and aortic outflow obstruction in 11%. Results Ten patients died before any intervention and 3 patients were lost to follow-up. Palliative procedures (includes 151 with systemic shunt, 27 pulmonary artery banding, 60 venous shunt) were performed in 203 patients, with 44 deaths, 8 patients awaiting Fontan, 12 patients Fontan contraindicated, and 11 patients lost-to-follow-up. A total of 137 patients had the Fontan procedure (9 patients without previous procedures) with 7 early deaths, 11 late deaths, and 3 patients progressing to heart transplantation. Total survival for the cohort was 90% at the age of 1 month, 81% at 1 year, 70% at 10 years, and 60% at 20 years with no significant change over the time period. Independent factors associated with ineligibility or death without Fontan (n = 68, 30%) included earlier birth date, lower birth weight, presence of aortic arch anomaly and greater right ventricular hypoplasia, and no palliative procedure. There were no significant changes in mortality with Fontan over the study time period with survival of 95% at 1 month, 93% at 1year, and 82% at 10 years. Conclusions Improvements in outcomes with tricuspid atresia will require attention to management and risk factors before Fontan.

Objectives: We sought to determine factors that would predict whether a biventricular repair or Norwood procedure pathway would give the best survival in neonates with critical aortic stenosis. Methods: Survival and risk factors were determined with parametric time-dependent event analysis for patients undergoing either the Norwood procedure or biventricular repair, and predicted optimal pathway and survival benefit were derived from multivariable linear regression. Results: From 1994 to 2000, 320 neonates with critical left ventricular outflow obstruction were entered into a prospective multi-institutional study. Patients who died without intervention (n = 19) and those with primary cardiac transplantation (n = 6) were excluded. An initial intended biventricular repair pathway was indicated in 116 patients, with survival of 70% at 5 years. An initial Norwood procedure was performed in 179 patients, with survival of 60% at 5 years. Using predictions from separate multivariable hazard models for survival with each of the 2 pathways, we determined predicted optimal pathway and survival benefit for each patient. Significant independent factors associated with greater survival benefit for the Norwood procedure versus biventricular repair included younger age at entry, lower z-score of the aortic valve and left ventricular length, higher grade of endocardial fibroelastosis, absence of important tricuspid regurgitation, and larger ascending aorta. Predicted survival benefit favored the Norwood procedure in 50% of patients who had biventricular repair, and it favored biventricular repair in 20% of patients who had the Norwood procedure. Conclusions: Morphologic and functional factors can be used to predict optimal pathway and survival benefit in neonates with critical left ventricular outflow obstruction. (J Thorac Cardiovasc Surg 2001;121:10-27)