Hepatoblastoma, the most common pediatric liver cancer, is tightly linked to excessive Wnt/beta-catenin signaling. Here, we used microarray analysis to identify two tumor subclasses resembling distinct phases of liver development and a discriminating 16-gene signature. beta-catenin activated different transcriptional programs in the two tumor types, with distinctive expression of hepatic stem/progenitor markers in immature tumors. This highly proliferating subclass was typified by gains of chromosomes 8q and 2p and upregulated Myc signaling. Myc-induced hepatoblastoma-like tumors in mice strikingly resembled the human immature subtype, and Myc downregulation in hepatoblastoma cells impaired tumorigenesis in vivo. Remarkably, the 16-gene signature discriminated invasive and metastatic hepatoblastomas and predicted prognosis with high accuracy.

Intracerebral cysts and porencephaly or arachnoid cysts are rarely but are repeatedly reported in orofaciodigital (OFD) syndrome type 1. We report on 2 families in which OFD syndrome type 1 was observed with central nervous system (CNS) malformations and 3 sporadic cases of OFD with CNS defects, most likely representing fresh mutations for OFD 1. In one case, vermis hypoplasia was present; in another, periventricular heterotopiae were noted. We review the literature on CNS anomalies in OFD syndromes and stress the difficulties in genetic counseling and functional prognosis for children of OFD 1 female carriers prenatally diagnosed with a malformation of the brain. As for CNS malformations, renal cystic disease is an often overlooked complication specific to OFD 1. In 1 family, cystic medullary disease was noted in OFD 1 carriers, leading 1 patient to dialysis by age 35 years and the other to severe renal insufficiency by age 28 years. Longitudinal follow-up of OFD 1 carriers should be performed, and renal function should be assessed in those with cysts because the functional prognosis of this developmental anomaly may be worse than usually reported in the literature.

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In the context of chronic physical child abuse, two entities have been described based on macroscopical and radiological criteria: the battered baby syndrome and the shaken baby syndrome. However, in some autopsy cases, clinico-radiological information may not be available. In these cases, histological examinations are necessary to look for sequelae of repeated haemorrhages, particularly in organs likely to have suffered traumatisms such as the lungs, or in organs belonging to the mononucleated macrophage resorption system, such as the liver and the spleen. We examined a series of 15 young children who died from proven chronic child abuse and compared them with 15 sex and age-matched control subjects who died from natural causes with no history of child abuse. Using Perl's stain for iron, we identified haemosiderin deposits in pulmonary, hepatic and splenic samples and the deposits were evaluated qualitatively and quantitatively. Haemosiderin deposits were significantly (P < 0.001) more abundant in the lungs and liver of the chronic abuse victims than in those of the control subjects. However, they were not significantly more abundant in the spleens of child abuse victims than in controls. We conclude that haemosiderin deposits in lungs and liver could be proposed as a marker for chronic physical child abuse. This study stresses the importance of systematic histological examination to look for pulmonary and hepatic haemosiderin deposits in cases in which chronic child abuse is suspected.