Legius syndrome, originally termed "neurofibromatosis type 1-like syndrome", is a condition characterized by changes in skin coloring pigmentation. Almost all affected individuals have multiple café-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. Freckles in the armpits and groin, may occur in some affected individuals.
Other signs and symptoms of Legius syndrome may include an abnormally large head and unusual facial characteristics. Although most people with Legius syndrome have normal intelligence, some affected individuals have been diagnosed with learning disabilities, ADD, or ADHD. Many of the signs and symptoms of Legius syndrome also occur in a similar disorder called neurofibromatosis type 1. An important difference is the absence of Lisch nodules and Neurofibromas which are common in NF1. Individuals frequently fulfill the NIH diagnostic criteria for NF1 based on pigmentary manifestations of café-au-lait spots and distinctive freckling patterns. A summary of overlapping symptoms was recently published by Muram-Zborovski et al.
Mutations in the SPRED1 gene cause Legius syndrome. The SPRED1 gene provides instructions for making the Spred-1 protein. This protein regulates an important cell signaling pathway that is involved in the growth and division of cells, the process by which cells mature to carry out specific functions, cell movement, and the self-destruction of cells. Mutations in the SPRED1 gene lead to a nonfunctional protein that can no longer regulate the pathway, resulting in overactive signaling. It is unclear how mutations in the SPRED1 gene cause the signs and symptoms of Legius syndrome.
Methodology: Sequencing of entire coding region
Purpose: Confirmation of Clinical Diagnosis
Test Requisition: Sequencing Requisition
CPT Code: 81405 Cost: $440.00
Turn-around-time: 3-4 weeks
1. Brems H, Chmara M, Sahbatou M, Denayer E, Taniguchi K, Kato R, Somers R, et al. (2007). “Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype”. Nat Genet. 39(9):1120-6.
2. Denayer E, Chmara M, Brems H, Kievit AM, van Bever Y, Van den Ouweland AM, et al. (2011). “Legius syndrome in fourteen families”. Hum Mutat. 32(1):E1985-98.
3. Messiaen L, Yao S, Brems H, Callens T, Sathienkijkanchai A, et al. (2009). “Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome”. JAMA. 302(19):2111-8.
4. Muram-Zborovski TM, Stevenson DA, Viskochil DH, Dries DC, Wilson AR, Rong Mao (2010). “SPRED 1 mutations in a neurofibromatosis clinic”. J Child Neurol. 25(10):1203-9.