EP05.23: Second trimester external hydrocephalus in Noonan syndrome with SOS1 gene mutation

Structural anomalies of central nervous system such as vermian hypoplasia, Chiari malformation and callosal dysgenesis have been described in Noonan syndrome (NS). An extremely rare finding, the prenatally presenting external hydrocephalus (EH) was described only in a single patient, with mutation of gene PTPN11 and never prenatally in mutation of gene SOS1. The aim of this case report is to describe a fetus with NS and EH. We report on a fetus at 20 week with negative cfDNA test, showing mildly dilated lateral ventricle (9mm), mild pyelectasy, polyhydramnion and larger head. The targeted neurosonography found altered Sylvian fissure- and Insula depths and concluded mild external hydrocephalus. Hypertelorism was also present, while typical NS structural anomalies (brain, heart or first trimester edema) where missing. Exome sequencing from amniotic fluid found a de novo pathogenic SOS1 (NM_005633.4:c.1644T>A) pSer548Arg mutation. This is the first case of Noonan syndrome prenatal diagnosis in a fetus presenting with external hydrocephalus and SOS1 mutation. The extent of EH became more evident in the third trimester and was also present after birth. The SOS1 gene mutations are linked to relatively normal development and stature compared to other NS types and the prenatal diagnosis is often difficult without significant structural ultrasound findings. We suggest to also consider NS related EH when neurosonographic measurements shows altered depths for the Sylvian fissure or for the Insula. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.