Legius syndrome

Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots.[3] It was first described in 2007 and is often mistaken for neurofibromatosis type I. It is caused by mutations in the SPRED1 gene.[5][6] It is also known as neurofibromatosis type 1-like syndrome.[1]

Legius syndrome
Other namesNeurofibromatosis 1-like syndrome[1]
This condition is inherited in an autosomal dominant manner.
Symptomscafé au lait spots; +/- learning disabilities[2]
Usual onsetat birth
CausesMutations in the SPRED1 gene[3]
Diagnostic methodClinical findings, Genetic test[4]
Differential diagnosisneurofibromatosis type I
TreatmentPhysical therapy, Speech therapy[2][1]
Prognosisgood
Frequencyrare (estimated at 1:46,000-1:75,000)[2]

Symptoms and signs
See also: List of conditions associated with café au lait macules
larger café au lait spot on right forearm

Nearly all individuals with Legius syndrome show multiple café au lait spots on their skin.[7] Symptoms may include:[2]

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.[1]

Cause
CHR 15

Legius syndrome is a phakomatosis[8] and a RASopathy, a developmental syndrome due to germline mutations in genes.[7][9] 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).[10][11] The gene in question demonstrates almost 100 mutations.[1]

Mechanism

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.[2][12]

Diagnosis

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.[4][1][13]

Differential diagnosis

The symptoms of Legius syndrome and neurofibromatosis type I are very similar; An important difference between Legius syndrome and neurofibromatosis type I is the absence of tumor growths Lisch nodules and neurofibromas which are common in neurofibromatosis type I.[2]

A genetic test is often the only way to make sure a person has Legius syndrome and not neurofibromatosis type I; 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.

Treatment

Management of Legius syndrome is done via the following:[2][1]

The prognosis of this condition is generally considered good with appropriate treatment.

See also

References
  1. RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Legius syndrome". www.orpha.net. Retrieved 2017-06-01.
  2. Stevenson, David; Viskochil, David; Mao, Rong (1993). "Legius Syndrome". GeneReviews. PMID 20945555. Retrieved 1 June 2017.update 2015
  3. "Legius syndrome", Genetics Home Reference, National Institutes of Health
  4. "Legius syndrome | Genetic and Rare Diseases Information Center". rarediseases.info.nih.gov. Retrieved 2017-06-01.
  5. "SPRED1", Genetics Home Reference, National Institutes of Health
  6. "Legius Syndrome Often Mistaken for Neurofibromatosis Type 1", by Allison Gandley, November 18, 2009, Medscape
  7. "OMIM Entry - # 611431 - LEGIUS SYNDROME". omim.org. Retrieved 2017-06-01.
  8. 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.
  9. 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.
  10. "OMIM Entry - * 609291 - SPROUTY-RELATED EVH1 DOMAIN-CONTAINING PROTEIN 1; SPRED1". www.omim.org. Retrieved 2017-06-01.
  11. "Homo sapiens sprouty related EVH1 domain containing 1 (SPRED1), RefSeq - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-06-01.
  12. 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.
  13. "SPRED1 sprouty related EVH1 domain containing 1 - Gene - GTR - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-06-01.
  14. Storebø, Ole Jakob; Storm, Maja Rosenberg Overby; Pereira Ribeiro, Johanne; Skoog, Maria; Groth, Camilla; Callesen, Henriette E.; Schaug, Julie Perrine; Darling Rasmussen, Pernille; Huus, Christel-Mie L.; Zwi, Morris; Kirubakaran, Richard; Simonsen, Erik; Gluud, Christian (2023-03-27). "Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD)". The Cochrane Database of Systematic Reviews. 2023 (3): CD009885. doi:10.1002/14651858.CD009885.pub3. ISSN 1469-493X. PMC 10042435. PMID 36971690.

Further reading
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