Legius syndrome and its link with Neurofibromatosis type 1.

12_Eric Legius_wbs.jpgEric Legius is professor in Human Genetics at the University of Leuven in Belgium and current head of the Department of Clinical Genetics at the University Hospital of Leuven. He is a clinician scientist.

His research is targeted towards Neurofibromatosis type 1 and related conditions. The research group contributed successfully towards the understanding of the molecular aetiology of a number of tumours in NF1. In 2007 his research team identified a new condition resembling Neurofibromatosis type 1, now known as Legius syndrome.

Legius syndrome is an autosomal dominant condition characterized by multiple café-au-lait spots and caused by heterozygous pathogenic variants in SPRED1. The SPRED1 protein is an important regulator of the ras-mapk pathway and the protein is needed to recruit neurofibromin (the protein produced by the NF1 gene) to the cell membrane where neurofibromin can downregulate activated ras. Legius syndrome and Neurofibromatosis type 1 are both characterized by multiple café-au-lait spots and the two conditions are very similar in children.

Recently diagnostic criteria for Legius syndrome and revised diagnostic criteria for Neurofibromatosis type 1 were published stressing the importance of molecular testing to differentiate the two diseases that affect the Ras-MAPK pathway in a similar way.

We will discuss the binding of SPRED1 to neurofibromin and the effect of missense variants in these regions in both genes on the function of the respective proteins. An important difference between the two diseases is the absence of Neurofibromatosis type 1 related tumours in Legius syndrome. A similarity is the effect on cognition and behaviour.