[Cardiofaciocutaneous syndrome, a Noonan syndrome related disorder: clinical and molecular findings in 11 patients].

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.

• Authors: Atilano Carcavilla, Sixto García-Miñaúr, Antonio Pérez-Aytés, Teresa Vendrell, Isabel Pinto, Encarna Guillén-Navarro, Antonio González-Meneses, Yoko Aoki, Daniel Grinberg, Begoña Ezquieta
• Journal: Medicina clinica (Med Clin (Barc)) Vol. 144 Issue 2 Pg. 67-72 (Jan 20 2015) ISSN: 1578-8989 [Electronic] Spain
• Vernacular Title: Síndrome cardiofaciocutáneo, un trastorno relacionado con el síndrome de Noonan: hallazgos clínicos y moleculares en 11 pacientes.
• PMID: 25194980 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Chemical References

• KRAS protein, human
• Proto-Oncogene Proteins
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• MAP Kinase Kinase 1
• MAP2K1 protein, human
• Proto-Oncogene Proteins p21(ras)
• ras Proteins

Topics

• Amino Acid Substitution
• Child
• Child, Preschool
• Cryptorchidism (genetics)
• DNA Mutational Analysis
• Dwarfism (genetics)
• Ectodermal Dysplasia (genetics, pathology)
• Facies
• Failure to Thrive (genetics, pathology)
• Female
• Genetic Heterogeneity
• Hair (pathology)
• Heart Defects, Congenital (genetics, pathology)
• Humans
• Infant
• Intellectual Disability (genetics)
• LEOPARD Syndrome (pathology)
• Language Development Disorders (genetics)
• MAP Kinase Kinase 1 (genetics)
• MAP Kinase Signaling System (physiology)
• Male
• Mutation, Missense
• Noonan Syndrome (pathology)
• Point Mutation
• Proto-Oncogene Proteins (genetics, physiology)
• Proto-Oncogene Proteins B-raf (genetics)
• Proto-Oncogene Proteins p21(ras)
• Skin (pathology)
• ras Proteins (genetics, physiology)