title: Are RASopathies new monogenic predisposing conditions to the development of systemic lupus erythematosus? Case report and systematic review of the literature.
abstract: OBJECTIVE
  RASopathies (Noonan syndrome (NS) and Noonan-related syndromes) are neurodevelopmental syndromes resulting from germline mutations in genes that participate in the rat sarcoma/mitogen-activated protein kinases (RAS/MAPK) pathway (PTPN11, SOS1, RAF, KRAS or NRAS, and SHOC2). Some monogenic conditions are associated with the development of systemic lupus erythematosus (SLE), and a few reports described the association of SLE with NS. We aim to search for a relationship between RASopathy and the development of SLE.
  
  
  METHODS
  We reported for the first time a case of 13-year-old boy with NS with loose anagen hair (NSLAH) resulting from mutation in SHOC2 who developed an autoimmune disorder that fulfilled four American College of Rheumatology (ACR) criteria for the classification of SLE (polyarthritis, pericarditis, antinuclear antibodies, and anti-DNA antibodies). The case report then prompted a literature review by a systematic search for English and French articles on the subjects of RASopathies and SLE that had English abstracts in PubMed from 1966 to 2012.
  
  
  RESULTS
  We identified seven additional patients with RASopathy and SLE. The male-to-female ratio was 1:1 and age at onset of SLE ranged from 5 to 32 years. The most common features were polyarthritis (7/8 patients), autoimmune cytopenia (4/8 patients), and pericarditis (4/8 patients) while only one patient presented with skin involvement.
  
  
  CONCLUSIONS
  The association of two rare diseases in eight patients suggests that RASopathies may be associated with the development of SLE, which is characterized by a higher male-to-female ratio, a lower rate of skin involvement, and a higher rate of pericarditis than "classic" SLE.
authors.affiliation: Department of Pediatric Immunology and Rheumatology, Necker enfants malades Hospital, Paris, France; INSERM U768, France; Imagine fundation, France. Electronic address: brigitte.bader-meunier@nck.aphp.fr.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bader-Meunier
authors.forename: Hélène
authors.initials: H
authors.lastname: Cavé
authors.forename: Nadia
authors.initials: N
authors.lastname: Jeremiah
authors.forename: Aude
authors.initials: A
authors.lastname: Magerus
authors.forename: Nina
authors.initials: N
authors.lastname: Lanzarotti
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rieux-Laucat
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
mesh_terms: D000293:Adolescent; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000235:genetics*; D008297:Male; D009154:Mutation; D009634:Noonan Syndrome / Q000150:complications / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C112913:SHOC2 protein, human
keywords: Lupus; Noonan; RASopathies