|This condition is inherited in an autosomal dominant manner.|
|Symptoms||café au lait spots; +/- learning disabilities|
|Usual onset||at birth|
|Causes||Mutations in the SPRED1 gene|
|Diagnostic method||Clinical findings, Genetic test|
|Differential diagnosis||neurofibromatosis type I (NF-1)|
|Treatment||Physical therapy, Speech therapy|
|Frequency||rare (estimated at 1:46,000-1:75,000)|
Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots. It was first described in 2007 and is often mistaken for neurofibromatosis type I (NF-1). It is caused by mutations in the SPRED1 gene. It is also known as neurofibromatosis type 1-like syndrome (NFLS).
Symptoms and signs
Nearly all individuals with Legius syndrome show multiple café au lait spots on their skin. Symptoms may include:
- Freckles in the axillary and inguinal skin fold
- Lipomas, developing in adulthood
- Learning disabilities
- Developmental delay
Features common in neurofibromatosis – like Lisch nodules (iris hamartomas diagnosed on slit lamp exam), bone abnormalities, neurofibromas, optic pathway gliomas and malignant peripheral nerve sheath tumors – are absent in Legius syndrome.
Legius syndrome is a phakomatosis and a RASopathy, a developmental syndrome due to germline mutations in genes. The condition is autosomal dominant in regards to inheritance and caused by mutations to the SPRED1 gene at chromosome 15, specifically 15q14 (or (GRCh38): 15:38,252,086-38,357,248). The gene in question demonstrates almost 100 mutations.
A mutated SPRED1 protein adversely regulates Ras-MAPK signaling, which is a chain of proteins in a cell that sends signals from the surface of a cell to the nucleus which in turn causes the symptoms of this condition.
Genetic testing is necessary to identify the syndrome. The DNA test is necessary sometimes, because symptoms may not be sufficient to definitely diagnose this condition.
The symptoms of Legius syndrome and NF-1 are very similar; An important difference between Legius syndrome and NF-1 is the absence of tumor growths Lisch nodules and neurofibromas which are common in NF-1.
A genetic test is often the only way to make sure a person has LS and not NF-1; the similarity of symptoms stem from the fact that the different genes affected in the two syndromes code for proteins that carry out a similar task in the same reaction pathway.[medical citation needed]
Management of Legius syndrome is done via the following:
- Physical therapy
- Speech therapy
- Pharmacologic therapy (e.g. methylphenidate for ADHD)
The prognosis of this condition is generally considered good with appropriate treatment.
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Legius syndrome". www.orpha.net. Archived from the original on 2017-11-16. Retrieved 2017-06-01.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Stevenson, David; Viskochil, David; Mao, Rong (1993). "Legius Syndrome". GeneReviews. PMID 20945555. Archived from the original on 10 September 2017. Retrieved 1 June 2017.update 2015
- ↑ 3.0 3.1 [https://web.archive.org/web/20170627230347/https://ghr.nlm.nih.gov/condition/legius-syndrome Archived 2017-06-27 at the Wayback Machine "Legius syndrome", Genetics Home Reference, National Institutes of Health
- ↑ 4.0 4.1 "Legius syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Archived from the original on 2017-01-14. Retrieved 2017-06-01.
- ↑ [https://web.archive.org/web/20180103193433/https://ghr.nlm.nih.gov/gene/SPRED1 Archived 2018-01-03 at the Wayback Machine "SPRED1", Genetics Home Reference, National Institutes of Health
- ↑ [https://web.archive.org/web/20191011202620/https://www.medscape.com/viewarticle/712643 Archived 2019-10-11 at the Wayback Machine "Legius Syndrome Often Mistaken for Neurofibromatosis Type 1", by Allison Gandley, November 18, 2009, Medscape
- ↑ 7.0 7.1 "OMIM Entry - # 611431 - LEGIUS SYNDROME". omim.org. Archived from the original on 2017-03-10. Retrieved 2017-06-01.
- ↑ Rosser, Tena (February 2018). "Neurocutaneous Disorders". Continuum (Minneapolis, Minn.). 24 (1, Child Neurology): 96–129. doi:10.1212/CON.0000000000000562. ISSN 1538-6899. PMID 29432239. S2CID 4107835. Archived from the original on 2021-06-02. Retrieved 2021-01-02.
- ↑ Tidyman, William (2009). "The RASopathies: Developmental syndromes of Ras/MAPK pathway dysregulation". Current Opinion in Genetics & Development. 19 (3): 230–236. doi:10.1016/j.gde.2009.04.001. PMC 2743116. PMID 19467855.
- ↑ "OMIM Entry - * 609291 - SPROUTY-RELATED EVH1 DOMAIN-CONTAINING PROTEIN 1; SPRED1". www.omim.org. Archived from the original on 2017-03-10. Retrieved 2017-06-01.
- ↑ "Homo sapiens sprouty related EVH1 domain containing 1 (SPRED1), RefSeq - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Archived from the original on 2018-01-24. Retrieved 2017-06-01.
- ↑ Molina, Julian R.; Adjei, Alex A. (2006-01-01). "The Ras/Raf/MAPK Pathway". Journal of Thoracic Oncology. 1 (1): 7–9. doi:10.1016/S1556-0864(15)31506-9. PMID 17409820.
- ↑ "SPRED1 sprouty related EVH1 domain containing 1 - Gene - GTR - NCBI". www.ncbi.nlm.nih.gov. Archived from the original on 2018-05-27. Retrieved 2017-06-01.
- ↑ Jakob Storebø Ole (2015). "Benefits and harms of methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD) | Cochrane". Reviews (11): CD009885. doi:10.1002/14651858.CD009885.pub2. PMID 26599576. Archived from the original on 2020-11-30. Retrieved 2021-01-02.
- MD, Robert P. Erickson; PhD, Anthony J. Wynshaw-Boris MD (2016). Epstein's Inborn Errors of Development: The Molecular Basis of Clinical Disorders of Morphogenesis. Oxford University Press. ISBN 9780190275426. Archived from the original on 28 August 2021. Retrieved 1 June 2017.
- Zhang, Jia (2016). "Molecular screening strategies for NF1-like syndromes with café-au-lait macules". Molecular Medicine Reports. 14 (5): 4023–4029. doi:10.3892/mmr.2016.5760. PMC 5112360. PMID 27666661. Review
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