Legius Syndrome

Legius syndrome is an autosomal dominantly inherited genetic disorder characterized by multiple café-au-lait spots with or without freckling. Heterozygous inactivating SPRED1 pathogenic variants are causing Legius syndrome. The same clinical phenotype can be seen in some families with neurofibromatosis type 1 (NF1). In the case of “pigmentary findings only” molecular analysis of the NF1 and SPRED1 genes is recommended to distinguish the two disorders. Both NF1 and Legius syndrome are caused by inactivating mutations in genes coding for proteins involved in the RAS/MAPK signaling pathway. Legius syndrome, however, is not associated with the typical tumors or bone abnormalities seen in NF1 and specific surveillance for these complications is not recommended. It is only recommended to monitor children for potential learning disabilities.