The echocardiographic findings and clinical courses in 19 fetuses with marked cardiomegaly [heart length, width, area, cardiothoracic ratio, heart/thoracic area (CTA) ratio > 2 SD] were reviewed. An abnormal heart was the reason for referral in 16 cases of 19 (84.2%). The mean gestational age was 31.5 weeks at detection. Intracardiac hemodynamics were studied using pulsed, color, and M-Mode color Doppler. Despite the heterogeneous etiology of marked cardiomegaly (5 Ebstein’s anomalies, 5 tricuspid valve dysplasias, 3 dilatative cardiomyopathies and 6 miscellaneous) a holosystolic tricuspid regurgitation with right atrial enlargement was found in 17 of the 19 cases (89.4%) as a common pathogenetic feature. A hydrops was found in 10 cases (52.6%). Besides 1 elective legal abortion, a high mortality rate of 83.3% was observed in the group followed up (6 intrauterine and 9 neonatal deaths). Among the cardiac measurements the CTA ratio seemed to correlate with fetal outcome, since all three survivors had the lowest values and all fetuses with CTA ratio > 0.6 showed a lung hypoplasia as a sequel of compression by cardiac enlargement. The presence or the development of hydrops, an obstruction of the right ventricular outflow tract, and the lung hypoplasia could be considered as signs of poor prognosis. A reliable differentiation between a patent pulmonary valve, pulmonary stenosis and pulmonary atresia in severe tricuspid regurgitation using modern Doppler means is difficult as seen in our studied group and in the literature. A cardiomegaly could be detected by nonexperienced examiners, but even if its presentation in fetal life could be considered as one of the main predictors of poor outcome, such cases have to be referred to centres experienced in fetal echocardiography.

Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, a dominantly inherited disorder of connective tissue that primarily involves the cardiovascular, ocular, and skeletal systems. There is a remarkable degree of variability both within and between families with Marfan syndrome, and FBN1 mutations have also been found in a range of other related connective tissue disorders collectively termed type-1 fibrillinopathies. FBN1 mutations have been found in almost all of the 65 exons of the FBN1 gene and for the most part have been unique to one affected patient or family. Aside from the "hot spots" for the neonatal Marfan syndrome in exons 24-27 and 31-32, genotype-phenotype correlations have been slow to emerge. Here we present the results of temperature-gradient gel electrophoresis analysis of FBN1 exons 59-65. Six mutations were identified, only one of which had been previously reported. Two of the six mutations were found in patients with mild phenotypes. Taken together with other published reports, our results suggest that a sizable subset (ca. 40%) of mutations in this region is associated with mild phenotypes characterized by the lack of significant aortic pathology, compared with about 7% in the rest of the gene. In two cases, mutations affecting analogous positions within one of the 43 cbEGF modules of FBN1 are associated with mild phenotypes when found in one of the 6 C-terminal modules (encoded by exons 59-63), but are associated with classic or severe phenotypes when found in cbEGF modules elsewhere in the gene.

We report on the prenatal diagnosis of ventriculo-coronary communication associated with pulmonary atresia and an intact interventricular septum. The diagnosis was made by transvaginal color Doppler sonography at 17 weeks' gestation and confirmed by transabdominal sonography at 19 weeks. Color Doppler demonstrated the communication between the distal hypoplastic right ventricle and the right coronary artery, with the course of this vessel situated along the outer heart wall. Spectral Doppler assessment showed bidirectional arterial flow in this vessel. Extracardiac skeletal anomalies (cleft hands and feet) were also detected and classified as an ectrodactyly-ectodermal dysplasia clefting (EEC) syndrome. This led the parents to opt for termination of pregnancy. All findings were confirmed on autopsy. Using stereomicroscopy the malformations of the coronary system and main connections to the lumen of the right ventricle were additionally demonstrated. To our knowledge this is the first report on the identification of coronary artery malformations in a midtrimester fetus using transvaginal color Doppler. The early appearance enabled us to investigate the pathophysiological sequence of the combined defect. Further investigation might elucidate whether ventriculo-coronary communications arise secondary to pulmonary atresia and intact inter-ventricular septum, due to increased ventricular pressure, or are the primary defect leading to intrauterine pulmonary atresia or, indeed, whether both defects appear simultaneously.