Fetomaternal hemorrhage (FMH) syndrome refers to a group of symptoms, including fetal anemia and maternal hemolytic transfusion reaction caused by fetal blood entering the maternal circulation through intervillous space. Diagnosis of FMH can be easily missed due to its non-specific symptoms and may lead to high perinatal mortality. The degree of fetal anemia and the volume of blood loss can be clinically evaluated by ultrasound measurement of middle cerebral artery peak systolic velocity and Kleihauer-Betke test. Clinical management is based on the degree of fetal anemia and gestational age. Intrauterine blood transfusion and termination are standard management. Fetal-maternal transfusion over 20 ml/kg is associated with fetal/neonatal morbidity or mortality. The incidence of FMH in twin pregnancy is rarely reported. We here report a case of dichorionic diamniotic twin pregnancy. Intrauterine death occurred to one of the twins because of FMH, and the other fetus was delivered at term with good outcome based on close monitoring.

BACKGROUNDVon Hippel-Lindau (VHL) syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various organs. The genetic basis of VHL in Southern Chinese is largely unknown. In this study, we characterized the mutation spectrum of VHL in nine unrelated Southern Chinese families.

METHODSNine probands with clinical features of VHL, two symptomatic and eight asymptomatic family members were included in this study. Prenatal diagnosis was performed twice for one proband. Two probands had only isolated bilateral phaeochromocytoma. The VHL gene was screened for mutations by polymerase chain reaction, direct sequencing and multiplex ligation-dependent probe amplification (MLPA).

RESULTSThe nine probands and the two symptomatic family members carried heterozygous germline mutations. Eight different VHL mutations were identified in the nine probands. One splicing mutation, NM_000551.2: c.463+1G > T, was novel. The other seven VHL mutations, c.233A > G [p.Asn78Ser], c.239G > T [p.Ser80Ile], c.319C > G [p.Arg107Gly], c.481C > T [p.Arg161X], c.482G > A [p.Arg161Gln], c.499C > T [p.Arg167Trp] and an exon 2 deletion, had been previously reported. Three asymptomatic family members were positive for the mutation and the other five tested negative. In prenatal diagnosis, the fetuses were positive for the mutation.

CONCLUSIONSGenetic analysis could accurately confirm VHL syndrome in patients with isolated tumours such as sporadic phaeochromocytoma or epididymal papillary cystadenoma. Mutation detection in asymptomatic family members allows regular tumour surveillance and early intervention to improve their prognosis. DNA-based diagnosis can have an important impact on clinical management for VHL families.

Asian Continental Ancestry Group ; DNA Mutational Analysis ; Humans ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; von Hippel-Lindau Disease ; genetics