Brachydactyly with extrahepatic biliary atresia, patent ductus arteriosus and seizures--a new syndrome?

Brachydactyly is a relatively common congenital anomaly and can be associated with many other malformations. However, brachydactyly in association with biliary atresia is rare. We present a male child with strikingly symmetrical brachydactyly and nail hypoplasia, extrahepatic biliary atresia, patent ductus arteriosus, seizures, developmental delay and cataracts. This combination of features has not previously been described and we suggest that this case represents a new syndrome.

Neutrophils from patients with heterozygous germline mutations in the von Hippel Lindau protein (pVHL) display delayed apoptosis and enhanced bacterial phagocytosis.

Neutrophils are key mediators of the innate immune response and are required to function at sites of low oxygenation. We have shown that in hypoxia neutrophils are protected from apoptosis via a mechanism dependent on prolyl hydroxylase domain/hypoxia-inducible factor 1alpha (PHD/HIF-1alpha). This response would be predicted to involve the von Hippel Lindau protein (pVHL)-dependent ubiquitination and degradation of HIF-1alpha. Patients with VHL disease inherit a mutation in one VHL allele, which allows us to study the effects of heterozygous VHL expression in human neutrophils. Neutrophils exhibited a striking "partial hypoxic" pheno-type, with delayed rates of apoptosis and enhanced bacterial phagocytosis under normoxic conditions and preserved responses to low levels of oxygen. This provides direct evidence that the HIF-1alpha/VHL pathway regulates the innate immune response in humans. It also establishes that heterozygous VHL defects are sufficient to perturb normal responses and illustrates the potential to use this to address the role of HIF and VHL in human biology.

Placental mesenchymal dysplasia associated with fetal aneuploidy.

OBJECTIVES: To describe three cases of placental mesenchymal dysplasia (PMD) associated with abnormal karyotype and review the cases reported in the literature. METHODS: The cases were retrieved from the files of three different institutions. A search of the English language literature was performed using Medline database. RESULTS: Placental abnormalities suggestive of molar changes were seen on the prenatal ultrasound scans. Histologically, the cases had large, hydropic stem villi with myxomatous stroma, cistern formation and 'chorangiomatoid' changes. The placental and fetal karyotypes identified were trisomy 13 (47,XX,t(1:13)(q32;q32)+ 13); Klinefelter syndrome (47,XXY) and triploidy (69,XXX). Including these 3 cases, of 66 reported cases, 51 (78%) were female and 14 (22%) male (ratio 3.6:1); the karyotype was normal in 32/36 (89%) and abnormal in 4/36 (11%); Beckwith-Wiedemann syndrome was confirmed or suspected in 15/66 (23%). Excluding termination of pregnancies, intrauterine death occurred in 18/54 (33%) cases. CONCLUSION: Molar ultrasonographic appearances associated with increased maternal serum alpha-fetoprotein but normal, or slightly elevated, levels of ss human Chorionic Gonadotrophin should raise the clinical suspicion of PMD. The diagnosis of this condition should not be disregarded when an abnormal fetus and/or an abnormal karyotype are demonstrated.