Severe Nerve Enlargement in SOS2-Related Noonan Syndrome

Noonan syndrome is a genetic multisystem congenital disorder, caused by pathogenic variants in genes that encode components of the RAS/MAPK signaling pathway. Pathogenic variants in SOS2 represent less than 2% of cases with NS. The phenotype includes a particularly high prevalence (65%) of lymphatic disease. Recently, severe nerve enlargements were described in patients with a pathogenic variant in SOS2. To establish the occurrence of nerve enlargements in SOS2-related Noonan syndrome, we retrospectively analyzed the data of all six patients with SOS2-related Noonan syndrome at our center. All patients had undergone high-resolution nerve ultrasound for clinical reasons, and all had enlarged nerves, most of them severe. All of our patients and the three patients with enlarged nerves described in three published case series have an amino acid substitution at p.Met267.