Atilano Carcavilla1, Sixto García-Miñaúr2, Antonio Pérez-Aytés3, Teresa Vendrell4, Isabel Pinto5, Encarna Guillén-Navarro6, Antonio González-Meneses7, Yoko Aoki8, Daniel Grinberg9, Begoña Ezquieta10. 1. Servicio de Pediatría, Hospital Virgen de la Salud, Toledo, España. Electronic address: atcarcavilla@gmail.com. 2. Instituto de Genética Médica y Molecular, Hospital La Paz, Madrid, España; Centro de Investigación Biomédica en Red en enfermedades raras (CIBERER). 3. Unidad de Genética Clínica, Hospital La Fe, Valencia, España. 4. Unidad de Genética Clínica, Hospital Vall d'Hebron, Barcelona, España. 5. Servicio de Pediatría, Hospital Severo Ochoa, Leganés, Madrid, España. 6. 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. 7. Unidad de Dismorfología, Servicio de Pediatría, Hospital Virgen del Rocío, Sevilla, España. 8. Departamento de Genética Médica, Facultad de Medicina, Universidad de Tohoku, Sendai, Japón. 9. 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. 10. 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.
Abstract
OBJECTIVES: 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). PATIENTS AND 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. DISCUSSION: 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.
OBJECTIVES: To describe 11 patients with cardiofaciocutaneous syndrome (CFC) and compare them with 130 patients with other RAS-MAPK syndromes (111 Noonan syndromepatients [NS] and 19 patients with LEOPARD syndrome). PATIENTS AND 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 CFCpatients when compared with other neuro-cardio-faciocutaneous syndromes (P<.05). In at least 2 cases molecular testing helped reconsider the diagnosis. DISCUSSION: CFCpatients 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: Amani Ali Davis; Giulio Zuccoli; Mostafa M Haredy; Joseph Losee; Ian F Pollack; Suneeta Madan-Khetarpal; Jesse A Goldstein; Ken K Nischal Journal: Glob Pediatr Health Date: 2019-05-12