We present a case of an infant prenatally diagnosed with bilateral outflow-tract obstruction and severe aortic regurgitation who underwent cardiac transplantation at 45 days of life. Aortico-left ventricular tunnel was subsequently diagnosed on pathologic examination of the explant heart. Aortico-left ventricular tunnel is a rare congenital cardiac malformation and can remain undiagnosed if the clinician has a low level of suspicion. Aortico-left ventricular tunnel should be considered in any fetus or newborn with aortic regurgitation.

Wilms tumor is the fourth most common malignancy of childhood; its pathogenesis, however, remains largely unknown. With advancements in cytogenetic techniques, such as array comparative genomic hybridization (aCGH), there is new hope for uncovering small chromosomal microdeletions or microduplications that may contribute to our understanding of Wilms tumor. We performed aCGH on 10 samples of Wilms tumor with normal conventional cytogenetic and chromosomal CGH findings. Array CGH revealed abnormalities in 3 of the 10 samples, including microdeletions (2q37.1, 7q31 approximately q32, and 11q22.3), microduplication (18q21.1), and gains and losses of larger chromosomal areas (1q and 7q gain and loss of 7p, 11q, 14q, and 16q). Fluorescence in situ hybridization (FISH) analysis confirmed the abnormalities and revealed the majority of them existed only in a proportion cells (> or =30% of cells). We also performed aCGH on three samples of Wilms tumor with previously identified translocations between chromosomes 1 and 16, to determine the breakpoints. The breakpoints were seen in the pericentromeric regions of both chromosomes. Array CGH is useful for identifying submicroscopic changes in Wilms tumor and is more sensitive for detecting clonal abnormalities than conventional methods.

We report two cases of arrhythmogenic right ventricular cardiomyopathy (ARVC) in the pediatric age group. In both cases, the diagnosis was considered and pursued but would not be made utilizing Task Force Criteria. The diagnosis was made based on the morphology of a single beat during exercise testing. We illustrate the difficulty of diagnosing ARVC in the young even with a heightened index of suspicion.

Mutations in SCO2, a metallochaperone involved in mitochondrial copper delivery, are associated with early onset, fatal hypertrophic cardiomyopathy. All reported patients carry at least one copy of the common 1541G>A (E140K) mutation. Whereas patients with one copy of the E140K allele, in combination with a more deleterious mutation, follow a severe clinical course, patients homozygous for the E140K mutation have a delayed onset of disease and a more prolonged survival. Here, we have investigated a patient who appeared homozygous for the common 1541G>A mutation based on DNA sequencing and restriction enzyme analysis of a PCR product, yet presented with early onset, severe cardiomyopathy. Restriction enzyme analysis of parental DNA revealed that the mother was heterozygous for 1541G>A, while the father was homozygous wild-type. The patient showed biparental inheritance for microsatellite markers spanning the length of chromosome 22, making isodisomy unlikely. Sequencing of several single nucleotide polymorphisms within the 5'-UTR, intron and single exon of the SCO2 gene was uninformative; however, a 16 bp deletion within the intron was present in the patient and the mother, but not the father. Restriction enzyme analysis confirmed that the mother was heterozygous and that the patient was hemizygous for the deletion. Southern blot, Northern blot, and FISH analyses were consistent with the de novo deletion of one allele of SCO2 in the patient. This is the first report of hemizygosity in a SCO2 patient. The patient phenotype underscores the strikingly similar clinical course in all patients with one copy of the E140K allele. Examination of both patient and parental genotypes by thorough molecular analyses can reveal information with important implications for genetic counseling.