Legius syndrome

Reviewed February 2011

What is Legius syndrome?

Legius 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. Another pigmentation change, 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 (macrocephaly) and unusual facial characteristics. Although most people with Legius syndrome have normal intelligence, some affected individuals have been diagnosed with learning disabilities, attention deficit disorder (ADD), or attention deficit hyperactivity disorder (ADHD).

Many of the signs and symptoms of Legius syndrome also occur in a similar disorder called neurofibromatosis type 1. It can be difficult to tell the two disorders apart in early childhood. However, the features of the two disorders differ later in life.

How common is Legius syndrome?

The prevalence of Legius syndrome is unknown. Many individuals with this disorder are likely misdiagnosed because the signs and symptoms of Legius syndrome are similar to those of neurofibromatosis type 1.

What genes are related to Legius syndrome?

Mutations in the SPRED1 gene cause Legius syndrome. The SPRED1 gene provides instructions for making the Spred-1 protein. This protein controls (regulates) an important cell signaling pathway that is involved in the growth and division of cells (proliferation), the process by which cells mature to carry out specific functions (differentiation), cell movement, and the self-destruction of cells (apoptosis). 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.

Related Gene(s)

Changes in this gene are associated with Legius syndrome.

SPRED1

How do people inherit Legius syndrome?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Where can I find information about diagnosis or management of Legius syndrome?

These resources address the diagnosis or management of Legius syndrome and may include treatment providers.

Children's Tumor Foundation: NF1 or Legius Syndrome--An Emerging Challenge of Clinical Diagnosis (http://www.ctf.org/Home/MyBlog/NF1-or-Legius-Syndrome-%E2%80%93-An-Emerging-Challenge-of-Clinical-Diagnosis.html)
Gene Review: Legius Syndrome (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=legius)
Genetic Testing Registry: Legius syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1969623)

You might also find information on the diagnosis or management of Legius syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/legius-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/legius-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Legius syndrome?

You may find the following resources about Legius syndrome helpful. These materials are written for the general public.

Educational resources - Information pages
University of Utah ARUP Laboratories (http://www.arup.utah.edu/database/SPRED1/SPRED1_welcome.php)
Patient support - For patients and families
Children's Tumor Foundation (http://www.ctf.org/)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=legius)
Genetic Testing Registry - Repository of genetic test information
- Genetic Testing Registry: Legius syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1969623)
ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?term=%22Legius%20syndrome%22%20%5BDISEASE%5D%20OR%20NCT00916903%20%5BID-NUMBER%5D)
PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((legius%20syndrome%5BTIAB%5D)%20OR%20(nfls%5BTIAB%5D)%20OR%20(neurofibromatosis%20type%201-like%20syndrome%5BTIAB%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/611431)

What other names do people use for Legius syndrome?

neurofibromatosis type 1-like syndrome
NFLS

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Legius syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Legius syndrome?

ADHD ; apoptosis ; attention deficit disorder ; attention deficit hyperactivity disorder ; autosomal ; autosomal dominant ; cell ; differentiation ; gene ; groin ; hyperactivity ; macrocephaly ; pigmentation ; prevalence ; proliferation ; protein ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

Brems H, Chmara M, Sahbatou M, Denayer E, Taniguchi K, Kato R, Somers R, Messiaen L, De Schepper S, Fryns JP, Cools J, Marynen P, Thomas G, Yoshimura A, Legius E. Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. Nat Genet. 2007 Sep;39(9):1120-6. Epub 2007 Aug 19. (http://www.ncbi.nlm.nih.gov/pubmed/17704776?dopt=Abstract)
Denayer E, Chmara M, Brems H, Kievit AM, van Bever Y, Van den Ouweland AM, Van Minkelen R, de Goede-Bolder A, Oostenbrink R, Lakeman P, Beert E, Ishizaki T, Mori T, Keymolen K, Van den Ende J, Mangold E, Peltonen S, Brice G, Rankin J, Van Spaendonck-Zwarts KY, Yoshimura A, Legius E. Legius syndrome in fourteen families. Hum Mutat. 2011 Jan;32(1):E1985-98. doi: 10.1002/humu.21404. (http://www.ncbi.nlm.nih.gov/pubmed/21089071?dopt=Abstract)
Gene Review: Legius Syndrome (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=legius)
Messiaen L, Yao S, Brems H, Callens T, Sathienkijkanchai A, Denayer E, Spencer E, Arn P, Babovic-Vuksanovic D, Bay C, Bobele G, Cohen BH, Escobar L, Eunpu D, Grebe T, Greenstein R, Hachen R, Irons M, Kronn D, Lemire E, Leppig K, Lim C, McDonald M, Narayanan V, Pearn A, Pedersen R, Powell B, Shapiro LR, Skidmore D, Tegay D, Thiese H, Zackai EH, Vijzelaar R, Taniguchi K, Ayada T, Okamoto F, Yoshimura A, Parret A, Korf B, Legius E. Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome. JAMA. 2009 Nov 18;302(19):2111-8. doi: 10.1001/jama.2009.1663. Erratum in: JAMA. 2010 Jun 23;303(24):2477. (http://www.ncbi.nlm.nih.gov/pubmed/19920235?dopt=Abstract)
Pasmant E, Sabbagh A, Hanna N, Masliah-Planchon J, Jolly E, Goussard P, Ballerini P, Cartault F, Barbarot S, Landman-Parker J, Soufir N, Parfait B, Vidaud M, Wolkenstein P, Vidaud D, France RN. SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype. J Med Genet. 2009 Jul;46(7):425-30. doi: 10.1136/jmg.2008.065243. Epub 2009 Apr 14. (http://www.ncbi.nlm.nih.gov/pubmed/19366998?dopt=Abstract)
Spurlock G, Bennett E, Chuzhanova N, Thomas N, Jim HP, Side L, Davies S, Haan E, Kerr B, Huson SM, Upadhyaya M. SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype. J Med Genet. 2009 Jul;46(7):431-7. doi: 10.1136/jmg.2008.065474. Epub 2009 May 13. (http://www.ncbi.nlm.nih.gov/pubmed/19443465?dopt=Abstract)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.



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