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.