Legius Syndrome and SPRED1  Genetics Home Reference

Mutations in the SPRED1 gene have been found in patients with Legius Syndrome, originally termed "neurofibromatosis type 1-like syndrome". Legius syndrome is caused by SPRED1 mutations on chromosome 15q13.2. Individuals frequently fulfill the NIH diagnostic criteria for NF1 based on pigmentary manifestations of café-au-lait spots and distinctive freckling patterns. This overlapping phenotype is likely due to increased Ras signal propagation caused by inactivating SPRED1 mutations. A summary of overlapping symptoms was recently published by Muram-Zborovski et al.

The phenotype due to SPRED1 mutations as described by Brems et al (2007) includes café-au-lait spots (98%), freckling (30%), and macrocephaly of >97th percentile (42%). Of the 44 reported cases (age range, 1-66 years) in these 5 families. Brems et al reported 14 patients with lipomas, 6 with learning problems, 5 with Noon-like facial features, 3 with depigmented spots, 2 with attention deficit and hyperactivity disorder, and 3 with pectus excavatum. Neurofibromas, Lisch nodules, optic pathway tumors, or malignant tumors were not identified. Three additional studies by Pasmant, Spurlock, and Messiaen reported similar phenotypes in patients with SPRED1 mutations. Spurlock et al tested 85 unrelated cases without detectable NF1 mutations or neurofibromas and identified 6 individuals with SPRED1 mutations.

The purpose of this database is to document all known SPRED1 mutations or gene variants including sequence based changes and large deletion/duplications that have been linked to Legius Syndrome, as well as any available associated clinical information or significant literature related to Legius Syndrome. The Genbank sequences NC_000015.9 and NM_152594.2 were used as ACVRL1 reference sequences.

Gene sequence analysis for the SPRED1 gene is offered as ARUP test 2002945, as well as test 2001961 for targeted sequencing of familial mutation.

Database Information

The SPRED1 database currently has 99 total entries.



Citations

When citing in publications please use:

Sumner K, Crockett DK, Muram T, Mallempati K, Best H, Mao R The SPRED1 Variants Repository for Legius Syndrome. G3(Bethesda). 2011 Nov;1(6):451-6.

Database URL:

http://www.arup.utah.edu/database/SPRED1/SPRED1_welcome.php