Legius syndrome has been estimated to occur with a prevalence of 1:46,000–1:75,000 and is caused by pathogenic variants in the SPRED1 gene located on chromosome 15q13.2 (Brems et al. 2007, 2012; Messiaen et al. 2009; Pasmant et al. 2009; Spurlock et al 2009; Laycock-van Spyk et al. 2011). Here, SPRED1 is linked to Legius syndrome.