EP18.14: The fetal brain in RASopathies: Noonan genes revisited

Although the neurodevelopmental variability among patients with RASopathies is well known, only recently have brain imaging features of these patients been studied. The fetal CNS phenotypic presentation of these entities is yet to be described. Our aim was to describe the fetal brain and associated features of fetuses with confirmed RASopathies. This retrospective study included fetuses with RASopathies confirmed by ES. Data on the variant involved, dedicated neurosonography, fetal MRI and echocardiography was assessed. Whenever inherited from a parent, parental brain imaging was also included in the analysis. Four patients with variants in RIT1, LZTR1, RRAS-2 and PTPN11 were included. 3 cases were inherited from a healthy parent. In 2 cases ES was performed in for an increased NT, and in 2 cases for polyhydramnios, and macrocephaly. All cases presented with enlarged extracerebral spaces, less pronounced in PTPN11 case. LTZR1 and RRAS2 cases featured macrocephaly in the 3rdT and abnormal gyration pattern. Severe polyhydramnios was feature of 3 cases. RRAS2 patient presented with severe overgrowth features and megalencephaly and was terminated. PTPN11 case had normal brain morphology. In all cases the TCD was large. No brain damage was observed. Corpus callosum was thin in all cases, and dysmorphic in 3. Also, variable degrees of facial dysmorphism was observed. In all cases AC was around or above 90th centile and femur around 5th centile. Associated extra-CNS findings differed between cases. Our study describes CNS and non-CNS features in RASopathies, and the variability between different entities. Fetal brain imaging presents a range of features that should be known as a clue for prenatal diagnosis specially in cases with abnormal NT, severe polyhydramnios, skin edema or large AC and HC with borderline FL and HL. Prenatal assessment of the fetal brain improves the diagnostic rate and is of utmost importance in prenatal counselling.