Legius syndrome

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

Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots.[2] 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.[5][6] It is also known as neurofibromatosis type 1-like syndrome (NFLS).[4]

Symptoms and signs

See also: List of conditions associated with café au lait macules

Nearly all individuals with Legius syndrome show multiple café au lait spots on their skin.[7] Symptoms may include:[1]

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.[4]

  • Legius syndrome
    Legius syndrome
  • Legius syndrome
    Legius syndrome
  • Café au lait spot on right underarm
    Café au lait spot on right underarm

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.[4]

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.[1][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.[3][4][13]

Differential diagnosis

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.[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.

Treatment

Management of Legius syndrome is done via the following:[1][4]

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

See also

References

  1. 1 2 3 4 5 6 7 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
  2. 1 2 [http://ghr.nlm.nih.gov/condition/legius-syndrome Archived 2017-06-27 at the Wayback Machine "Legius syndrome", Genetics Home Reference, National Institutes of Health
  3. 1 2 "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.
  4. 1 2 3 4 5 6 RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Legius syndrome". www.orpha.net. Archived from the original on 2017-11-16. Retrieved 2017-06-01.
  5. ↑ [http://ghr.nlm.nih.gov/gene/SPRED1 Archived 2018-01-03 at the Wayback Machine "SPRED1", Genetics Home Reference, National Institutes of Health
  6. ↑ [http://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. 1 2 "OMIM Entry - # 611431 - LEGIUS SYNDROME". omim.org. Archived from the original on 2017-03-10. 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. Archived from the original on 2021-06-02. Retrieved 2021-01-02.
  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. Archived from the original on 2017-03-10. Retrieved 2017-06-01.
  11. ↑ "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.
  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. Archived from the original on 2018-05-27. Retrieved 2017-06-01.
  14. ↑ 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.

Further reading

Classification
External resources
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