Legius syndrome is very similar to NF1 with regard to dermal manifestations. Nearly all patients exhibit multiple café au lait spots, and many patients also have intertriginous flecking in the region of the armpit and/or groin. Other clinical features of NF1 are absent from Legius syndrome, however.
In a few patients with Legius syndrome, psychomotor developmental delays are described as learning disabilities, particularly 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, described as hemangiomas or vascular malformations.
In individual cases, leukemia is reported in connection with Legius syndrome. Since SPRED1 is part of the RAS/MAPK signaling pathway, an increased risk of neoplasia is suspected when there are mutations in this gene. Due to the limited number of patients with the disease, it has not yet been possible to verify this assumption.