Proliferation-independent role of NF2 (merlin) in limiting biliary morphogenesis.

The architecture of individual cells and cell collectives enables functional specification, a prominent example being the formation of epithelial tubes that transport fluid or gas in many organs. The intrahepatic bile ducts (IHBDs) form a tubular network within the liver parenchyma that transports bile to the intestine. Aberrant biliary 'neoductulogenesis' is also a feature of several liver pathologies including tumorigenesis. However, the mechanism of biliary tube morphogenesis in development or disease is not known. Elimination of the neurofibromatosis type 2 protein (NF2; also known as merlin or neurofibromin 2) causes hepatomegaly due to massive biliary neoductulogenesis in the mouse liver. We show that this phenotype reflects unlimited biliary morphogenesis rather than proliferative expansion. Our studies suggest that NF2 normally limits biliary morphogenesis by coordinating lumen expansion and cell architecture. This work provides fundamental insight into how biliary fate and tubulogenesis are coordinated during development and will guide analyses of disease-associated and experimentally induced biliary pathologies.

Neonatal liver cirrhosis without iron overload caused by gestational alloimmune liver disease.

Gestational alloimmune liver disease has emerged as the major cause of antenatal liver injury and failure. It usually manifests as neonatal liver failure with hepatic and extrahepatic iron overload, a clinical presentation called neonatal hemochromatosis. We report on a newborn in whom fetal hepatomegaly was detected during pregnancy and who presented at birth with liver cirrhosis and mild liver dysfunction. Liver biopsy showed the absence of iron overload but strong immunostaining of hepatocytes for the C5b-9 complex, the terminal complement cascade neoantigen occurring specifically during complement activation by the immunoglobulin G-mediated classic pathway, which established the alloimmune nature of the hepatocyte injury. The infant survived with no specific therapy, and follow-up until 36 months showed progressive normalization of all liver parameters. This case report expands the recognized clinical spectrum of congenital alloimmune liver disease to include neonatal liver disease and cirrhosis, even in the absence of siderosis. Such a diagnosis is of utmost importance regarding the necessity for immunotherapy in further pregnancies to avoid recurrence of alloimmune injury.

[Fetal hepatosplenomegaly in the third trimester: A sign of leukemia in fetuses with Down syndrome]. / Hépatosplénomégalie fœtale au troisième trimestre : un signe d'appel de leucémie chez les fœtus porteurs de trisomie 21.

Risk for leukemic conditions increases in individuals with Down syndrome. We report a third trimester antenatal diagnosis of leukemia in a Down syndrome fetus. The third trimester ultrasound examination revealed a hepatosplenomegaly, which may suggest a myelopoiesis disorder. A review of the literature of eight cases described antenatally and 14 cases in the immediate neonatal period is presented.

Prenatal sonographic findings and hematological abnormalities in fetuses with transient abnormal myelopoiesis with Down syndrome.

OBJECTIVES: To determine relevant prenatal findings of transient abnormal myelopoiesis (TAM) that have important prognostic implications. METHODS: The prenatal and postnatal medical records of all cases with confirmed TAM associated with Down syndrome were reviewed retrospectively, with emphasis on prenatal sonographic findings, fetal blood analysis, neonatal outcomes, and causes of death. RESULTS: From January 1992 to December 2005, seven cases were confirmed postnatally as having TAM associated with Down syndrome. Sonography demonstrated hydrops with hepatomegaly in four, and isolated hepatomegaly in two of these seven cases. There were no findings suggestive of cardiac failure in cases of hydrops. Fetal blood analysis revealed elevated liver enzyme levels in six cases and hypoalbuminemia in four cases. Comparison of sonographic findings with fetal blood findings demonstrated an association between hydrops and hypoalbuminemia. Four of the seven cases were fatal. All fatal cases were associated with hydrops and the main cause of death was coagulopathy due to liver failure, which may have resulted from infiltration of the liver by blast cells. CONCLUSIONS: Fetal TAM is associated with hepatomegaly and elevated liver enzyme levels. The prenatal finding with prognostic implications is hydrops, which may result from hypoalbuminemia due to liver failure.

Unusual prenatal presentation of Beckwith-Wiedemann syndrome.

When Beckwith-Wiedemann syndrome (BWS) is detected prenatally, it is usually on the basis of macroglossia, exomphalos or enlarged kidneys. We describe a case that presented as gross hepatomegaly and a suspected enlarged pancreas at 20 weeks' gestation, with none of the usual features.