title: [Cardiofaciocutaneous syndrome, a Noonan syndrome related disorder: clinical and molecular findings in 11 patients].
abstract: OBJECTIVE
  To describe 11 patients with cardiofaciocutaneous syndrome (CFC) and compare them with 130 patients with other RAS-MAPK syndromes (111 Noonan syndrome patients [NS] and 19 patients with LEOPARD syndrome).
  
  
  METHODS
  Clinical data from patients submitted for genetic analysis were collected. Bidirectional sequencing analysis of PTPN11, SOS1, RAF1, BRAF, and MAP2K1 focused on exons carrying recurrent mutations, and of all KRAS exons were performed.
  
  
  RESULTS
  Six different mutations in BRAF were identified in 9 patients, as well as 2 MAP2K1 mutations. Short stature, developmental delay, language difficulties and ectodermal anomalies were more frequent in CFC patients when compared with other neuro-cardio-faciocutaneous syndromes (P<.05). In at least 2 cases molecular testing helped reconsider the diagnosis.
  
  
  CONCLUSIONS
  CFC patients showed a rather severe phenotype but at least one patient with BRAF mutation showed no developmental delay, which illustrates the variability of the phenotypic spectrum caused by BRAF mutations. Molecular genetic testing is a valuable tool for differential diagnosis of CFC and NS related disorders.
authors.affiliation: Servicio de Pediatría, Hospital Virgen de la Salud, Toledo, España. Electronic address: atcarcavilla@gmail.com.
authors.forename: Atilano
authors.initials: A
authors.lastname: Carcavilla
authors.affiliation: Instituto de Genética Médica y Molecular, Hospital La Paz, Madrid, España; Centro de Investigación Biomédica en Red en enfermedades raras (CIBERER).
authors.forename: Sixto
authors.initials: S
authors.lastname: García-Miñaúr
authors.affiliation: Unidad de Genética Clínica, Hospital La Fe, Valencia, España.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pérez-Aytés
authors.affiliation: Unidad de Genética Clínica, Hospital Vall d'Hebron, Barcelona, España.
authors.forename: Teresa
authors.initials: T
authors.lastname: Vendrell
authors.affiliation: Servicio de Pediatría, Hospital Severo Ochoa, Leganés, Madrid, España.
authors.forename: Isabel
authors.initials: I
authors.lastname: Pinto
authors.affiliation: Centro de Investigación Biomédica en Red en enfermedades raras (CIBERER); Unidad de Genética Médica, Servicio de Pediatría, Hospital Virgen de la Arrixaca, Cátedra de Genética Médica, Universidad Católica San Antonio de Murcia, Murcia, España.
authors.forename: Encarna
authors.initials: E
authors.lastname: Guillén-Navarro
authors.affiliation: Unidad de Dismorfología, Servicio de Pediatría, Hospital Virgen del Rocío, Sevilla, España.
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Meneses
authors.affiliation: Departamento de Genética Médica, Facultad de Medicina, Universidad de Tohoku, Sendai, Japón.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Centro de Investigación Biomédica en Red en enfermedades raras (CIBERER); Departamento de Genética, Facultad de Biología, Universidad de Barcelona, Instituto de Biomedicina de la Universitad de Barcelona (IBUB), Barcelona, España.
authors.forename: Daniel
authors.initials: D
authors.lastname: Grinberg
authors.affiliation: Centro de Investigación Biomédica en Red en enfermedades raras (CIBERER); Laboratorio Diagnóstico Molecular, Servicio de Bioquímica, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, España.
authors.forename: Begoña
authors.initials: B
authors.lastname: Ezquieta
mesh_terms: D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D003456:Cryptorchidism / Q000235:genetics; D004252:DNA Mutational Analysis; D004392:Dwarfism / Q000235:genetics; D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000473:pathology; D019066:Facies; D005183:Failure to Thrive / Q000235:genetics* / Q000473:pathology; D005260:Female; D018740:Genetic Heterogeneity; D006197:Hair / Q000473:pathology; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D044542:LEOPARD Syndrome / Q000473:pathology; D007805:Language Development Disorders / Q000235:genetics; D048369:MAP Kinase Kinase 1 / Q000235:genetics*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D020125:Mutation, Missense; D009634:Noonan Syndrome / Q000473:pathology; D017354:Point Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012867:Skin / Q000473:pathology; D018631:ras Proteins / Q000235:genetics / Q000502:physiology
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: BRAF; Cardiofaciocutaneous syndrome; Correlación genotipo-fenotipo; Estenosis pulmonar valvular; Genotype-phenotype correlation; Hypertrophic cardiomyopathy; LEOPARD syndrome; MAP2K1; Miocardiopatía hipertrófica; Noonan syndrome; PTPN11; Pulmonary valve stenosis; RAS-MAPK pathway; Rasopathy; Rasopatía; Síndrome LEOPARD; Síndrome cardiofaciocutáneo; Síndrome de Noonan; Vía RAS-MAPK