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]

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]

Symptoms and signs

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. 1 2 3 4 5 6 7 RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Legius syndrome". www.orpha.net. Retrieved 2017-06-01.{{cite web}}: CS1 maint: numeric names: authors list (link)
  2. 1 2 3 4 5 6 7 Stevenson, David; Viskochil, David; Mao, Rong (1993). "Legius Syndrome". GeneReviews. PMID 20945555. Retrieved 1 June 2017.update 2015
  3. 1 2 "Legius syndrome", Genetics Home Reference, National Institutes of Health
  4. 1 2 "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. 1 2 "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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