Legius Syndrome

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OMIM 57 611431 Orphanet 59 ORPHA137605 MESH via Orphanet 45 C548032 UMLS via Orphanet 74 C1969623 ICD10 via Orphanet 34 Q85.0

MedGen 42 C1969623 MeSH 44 D019080 KEGG 37 H01986 SNOMED-CT via HPO 69 263681008 27272007 194021007 22006008 32958008 95427009 246800008 11934000 201281002 51089004 404062002 46720004 93163002 19133005 81669005 406506008 7461003 more UMLS 73 C1969623

NIH Rare Diseases : ⁵³ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 137605Disease definitionLegius syndrome, also known as NF1-like syndrome, is a rare, genetic skin pigmentation disorder characterized by multiple café-au-lait macules with or without axillary or inguinal freckling.EpidemiologyThe prevalence of Legius syndrome is not known. Fewer than 200 cases have been reported to date. Prevalence may be higher than expected due to misdiagnosis of cases as neurofibromatosis type 1 (NF1, see this term). The incidence of NF1 is reported to be 1/3000, and about 2% of patients fulfilling diagnostic criteria for NF1 are found to have the genetic mutation underlying Legius syndrome (SPRED1).Clinical descriptionThe clinical presentation of Legius syndrome is very similar to that of NF1. Patients typically present with multiple café-au-lait spots sometimes associated with intertriginous freckling, but lack Lisch nodules, optic pathway gliomas, bone abnormalities, neurofibromas or other tumor manifestations. The number of café-au-lait macules tends to increase with age during childhood. Other less common manifestations include short stature, macrocephaly, Noonan-like facies, pectus excavatum/carinatum, lipomas, hypopigmented macules, vascular lesions, learning disabilities, attention deficit/hyperactivity disorder (ADHD), and developmental delay.EtiologyLegius syndrome is caused by heterozygous inactivating mutations in the SPRED1 gene (15q14), involved in regulation of the RAS-MAPK signal transduction pathway. Nearly 100 different mutations in this gene have been identified. The proportion of cases related to de novo mutations is not yet known. No genotype-phenotype correlations have been found.Diagnostic methodsAbout 50% of patients with Legius syndrome fulfill the diagnostic criteria for NF1, but they have a far milder phenotype compared to NF1 patients. Diagnosis based solely on the presence of clinical features is difficult, given the overlap with other disorders characterized by multiple café-au-lait spots. The presence of characteristic clinical signs in parents of affected individuals is supportive of diagnosis. However, molecular genetic testing is required to confirm the diagnosis and testing is available on a clinical basis.Differential diagnosisLegius syndrome is differentiated from NF1 by the absence of the non-pigmentary clinical manifestations seen in this disorder (i.e. Lisch nodules, neurofibromas, optic glioma, bone abnormalities). Correct diagnosis is essential because of the differences in prognosis and long-term monitoring between Legius syndrome and NF1. Other disorders to consider include Noonan syndrome, Noonan syndrome with lentigines (LEOPARD syndrome), and McCune-Albright syndrome (see these terms).Antenatal diagnosisPrenatal diagnosis is possible and requires prior identification of the disease-causing mutation in the family.Genetic counselingLegius syndrome follows an autosomal dominant pattern of inheritance. Genetic counseling should be provided to affected families.Management and treatmentDrug therapy should be considered for the behavioral manifestations of the disorder (ADHD). Physical, speech, and occupational therapy is recommended for those with developmental delay and educational support for those with learning difficulties.PrognosisGiven the current knowledge of disease manifestations and complications, the prognosis for patients with Legius syndrome is considered to be very good.Visit the Orphanet disease page for more resources.

MalaCards based summary : Legius Syndrome, also known as neurofibromatosis type 1-like syndrome, is related to noonan syndrome 1 and neurofibromatosis, type iv, of riccardi. An important gene associated with Legius Syndrome is SPRED1 (Sprouty Related EVH1 Domain Containing 1), and among its related pathways/superpathways are Cytokine Signaling in Immune system and Negative regulation of FGFR3 signaling. Affiliated tissues include skin, testes and bone, and related phenotypes are high palate and macrocephaly

Genetics Home Reference : ²⁵ 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.

OMIM : ⁵⁷ Legius syndrome is an autosomal dominant disorder that shows some similarities to neurofibromatosis type I (NF1; 162200), which is caused by mutation in the neurofibromin gene (613113); however, Legius syndrome is less severe. Individuals with Legius syndrome typically have multiple cafe-au-lait spots, sometimes associated with skin fold freckling, variable dysmorphic features such as hypertelorism or macrocephaly, lipomas, and mild learning disabilities or attention problems. Legius syndrome is not associated with neurofibromas, optic gliomas, Lisch nodules, or tumor predisposition. The SPRED1 gene encodes a negative regulator of the RAS-MAPK pathway, similar to neurofibromin, and thus may be considered a RASopathy (review by Brems et al., 2012). (611431)

UniProtKB/Swiss-Prot : ⁷⁵ Neurofibromatosis 1-like syndrome: A disorder characterized mainly by cafe au lait macules without neurofibromas or other tumor manifestations of neurofibromatosis type 1, axillary freckling, and macrocephaly. Additional clinical manifestations include Noonan-like facial dysmorphism, lipomas, learning disabilities and attention deficit-hyperactivity.

Wikipedia : ⁷⁶ Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots. It was... more...

GeneReviews: NBK47312

Clinical features from OMIM:

611431

Search NIH Clinical Center for Legius Syndrome

Search GEO for disease gene expression data for Legius Syndrome.