In some isolated cases, Legius syndrome has been associated with leukemia. It is known that various defects or changes in a specific signaling pathway (RAS/MAPK signaling pathway) inside our body’s cells result in an increased risk of developing cancer. The mutation responsible for Legius syndrome also affects this signaling pathway, which suggests that there is an increased risk of malignant diseases. Due to the low number of patients, however, it has not yet been possible to confirm this assumption.
Legius syndrome is very similar to NF1 with regard to manifestations of the skin. Nearly all patients exhibit numerous café au lait spots, and many patients also have intertriginous freckling in the armpit and/or groin region. The additional clinical features of NF1 are however lacking in the case of Legius syndrome.
In a few patients with Legius syndrome, psychomotor developmental delays are described as a learning disability, specifically affecting speech. ADHD has also been reported as part of the disease. Overall, however, patients with Legius syndrome appear to be less restricted cognitively than patients with NF1.
In addition, a few patients also exhibit vascular changes.