Prenatal diagnosis of Noonan syndrome in fetuses with increased nuchal translucency and a normal karyotype.

OBJECTIVE: Noonan syndrome (NS), one of the most common RASopathies, has an estimated incidence of 1 in 1,000-2,500 live births. In the prenatal period increased nuchal translucency, hygroma colli, hydrops fetus, congenital heart disease, kidney defects, larger amount of amniotic fluid can be observed in affected fetuses with this syndrome. In the fetuses with normal karyotype and no microdeletion/microduplication syndromes the examination of selected genes for RASopathies was added. The aim of the study was to evaluate the clinical benefit of massively parallel sequencing (MPS) of susceptible fetal DNA for NS, i.e., the diagnostic yield on the one hand and the proportion of detected variants of unknown significance (VOUS) on the other. DESIGN: Clinically diagnostic. SETTING: Centrum prenatální diagnostiky, Brno, s.r.o; Cytogenetická laboratoř Brno, s.r.o. METHODS: Samples of amniotic fluid or chorionic villus were analyzed. Selected genes associated with RASopathies were analyzed in case of the negative result of karyotype and array-CGH. A panel of twenty genes was investigated by MPS. RESULTS: In the two-years period, Noonan syndrome was detected in 10 from 95 investigated fetuses. This represents a 10.5% diagnostic efficiency of the method. DNA variants of unknown significance were detected in 10 fetuses. A segregation analysis helped to clarify their meaning in six fetuses. CONCLUSION: MPS allows fast molecular-genetic diagnosis of RASopathies already in the prenatal period. This method contributes to the clarification not only of phenotypic manifestations in already born individuals but also of ultrasound findings in fetuses with both normal karyotype and aCGH.

Non-invasive fetal RHD and RHCE genotyping from maternal plasma in alloimmunized pregnancies.

BACKGROUND: In this prospective study, we assessed the feasibility of fetal RH genotyping by analysis of DNA extracted from maternal plasma samples of alloimmunized pregnant women using real-time PCR and primers and probes targeted toward RHD (exon 7 and exon 10) and RHCE (intron 2 and exon 5) genes. METHODS: We analysed 23 alloimmunized pregnant women (16 anti-D, 5 anti-D + C, 2 anti-E) at risk of haemolytic disease of the newborn (HDN) within 11th and 37th week of pregnancy and correlated the results with serological analysis of cord blood. RESULTS AND CONCLUSION: Detection of the presence of the RHD gene, the C and/or E alleles of the RHCE gene in maternal plasma samples is highly accurate and enables implementation in a clinical diagnostic algorithm for following pregnancies at risk for HDN. The absence of RHD gene, the C and/or E alleles of RHCE gene in the current pregnancy excludes the risk of HDN caused by anti-D, anti-C and/or anti-E alloantibodies and the performance of invasive fetal-blood sampling.

[Prenatal use of a vesico-amniotic shunt in obstructive uropathy]. / Prenatální aplikace vezikoamniálního shuntu pri obstrukcní uropatii.

Obstructive uropathy was diagnosed in a fetus in the 31st week of gestation. Good renal functioning and a low L/S index (lecithin/sphingomyelin) in amniotic fluid having been found, a vesocoamniotic shunt was inserted percutaneously. Draining through the shunt lasted for three weeks; then the gravidity was terminated due to stent dislocation while the lung maturity was good. After delivery, right kidney afunction, 4th-5th degree reflux and left-sided hydroureter were diagnosed. At the age of one year, nephrectomy on the right, left-sided hydroureter resection and plastic correction of the megaloureter on the right were performed. The child's condition is satisfactory.