Fatal congenital hypertrophic cardiomyopathy and a pancreatic nodule morphologically identical to focal lesion of congenital hyperinsulinism in an infant with costello syndrome: case report and review of the literature.

Costello syndrome is characterized by constitutional mutations in the proto-oncogene HRAS, causing dysmorphic features, multiple cardiac problems, intellectual disability, and an increased risk of neoplasia. We report a male infant with dysmorphic features, born prematurely at 32 weeks, who, during his 3-month life span, had an unusually severe and ultimately fatal manifestation of hypertrophic cardiomyopathy and hyperinsulinemic hypoglycemia. Molecular studies in this patient demonstrated the uncommon Q22K mutation in the HRAS gene, diagnostic of Costello syndrome. The major autopsy findings revealed hypertrophic cardiomyopathy, congenital myopathy, and a 1.4-cm pancreatic nodule that was positive for insulin expression and morphologically identical to a focal lesion of congenital hyperinsulinism. Sequencing of KCNJ11 and ABCC8, the 2 most commonly mutated genes in focal lesion of congenital hyperinsulinism, revealed no mutations. While hyperinsulinism is a recognized feature of RASopathies, a focal proliferation of endocrine cells similar to a focal lesion of hyperinsulinism is a novel pathologic finding in Costello syndrome.

Systolic and diastolic function of the fetal single left ventricle.

BACKGROUND: The functionally single fetal right ventricle demonstrates reduced longitudinal relative to circumferential contraction velocities and deformation, a pattern similar to the normal fetal left ventricle. Altered diastolic properties are also present, with greater reliance on atrial contraction for right ventricular filling. It is unknown whether the functionally single left ventricle (SLV) demonstrates similar altered deformation patterns and diastolic properties. METHODS: Echocardiograms from 29 fetuses with SLVs were retrospectively compared with those from 48 controls with appropriately grown left ventricles. Ventricular function was assessed using Velocity Vector Imaging velocity, tissue deformation, two-dimensional, and Doppler flow parameters. RESULTS: Fetuses with functionally SLVs showed no difference in peak global left ventricular longitudinal velocity or displacement or strain, while global radial displacement was increased (P < .001). The ratio of longitudinal to circumferential deformation was also no different from that in controls. The SLVs showed increased diameters (P < .001) with normal lengths. Mitral inflow peak E-wave (P < .05) and A-wave (P < .0001) velocities were increased, with a reduced E/A ratio (P < .001). A-wave inflow fraction was also increased (P < .05), with no change in A duration. Although ejection time was no different, inflow duration was increased (P < .01) and there was a trend toward reduction of the Tei index (P = .07). CONCLUSIONS: The functionally single fetal left ventricle shows comparable changes to the single right ventricle, with a more spherical morphology and greater reliance on atrial contraction for ventricular filling than in controls. However, in contrast to the single right ventricle, the SLV had a normal longitudinal to circumferential deformation ratio with enhanced early diastolic filling.

Right ventricular function in fetal hypoplastic left heart syndrome.

BACKGROUND: The systemic right ventricle in palliated hypoplastic left heart syndrome (HLHS) has relatively reduced longitudinal compared with circumferential deformation, a pattern of contraction more akin to the normal left ventricle, which presumably improves right ventricular (RV) pumping efficiency. The aim of this study was to test the hypothesis that these changes in the RV contraction pattern in infants with HLHS are present prenatally. METHODS: Echocardiograms from 48 fetuses with HLHS were retrospectively compared with those from appropriately grown RV and left ventricular controls. Ventricular function was assessed using Velocity Vector Imaging velocity, tissue deformation, two-dimensional echocardiography, and Doppler flow parameters. RESULTS: Fetuses with HLHS demonstrated reduced peak global RV longitudinal velocity (P < .01), strain (P < .001), and displacement (P < .05), while radial displacement was increased (P < .001) compared with the normal fetal right ventricle. Mean RV diameter was increased in HLHS (P < .001), but length was unchanged. The ratio of longitudinal to circumferential deformation was reduced in HLHS compared with the normal right ventricle (P < .001) and equivalent to the normal left ventricle. Tricuspid inflow peak A-wave velocity (P < .01), A-wave duration, A-wave inflow fraction, RV Tei index (P < .05 for all), and inferior vena cava A-wave reversal (P < .0001) were increased in HLHS. CONCLUSIONS: The fetal right ventricle in HLHS becomes more spherical because of increased RV diameter. It has relatively reduced longitudinal compared with circumferential deformation and an increased reliance on atrial contraction for ventricular filling. These findings are similar to postnatal changes observed in the systemic right ventricle in palliated congenital heart disease, suggesting that ventricular remodeling is initiated in fetal life.

Management of the sick neonate with suspected heart disease.

A proportion of symptomatic neonates with congenital heart disease have lesions requiring urgent stabilisation. Despite increasing antenatal diagnoses, the importance of early recognition of symptomatic neonates is highlighted by the fact that up to 10% of all deaths in congenital heart disease continue to occur in children undiagnosed at the time of death. Specific anatomical knowledge of the many complex lesions is not required for good early management. The focus of this article is the specific symptom complexes in critically ill neonates with congenital heart disease, initial management strategies for stabilization and transfer to specialist centres, and issues in the ongoing preoperative care.