title: Further evidence of genetic heterogeneity in Costello syndrome: involvement of the KRAS gene.
abstract: Costello syndrome is an autosomal dominant disorder comprising growth deficiency, mental retardation, curly hair, coarse facial features, nasal papillomata, low-set ears with large lobes, cardiac anomalies, redundant skin in palms and soles with prominent creases, dark skin, and propensity to certain solid tumors. HRAS mutations have been implicated in approximately 85% of the affected cases. The clinical overlap among Costello, Noonan, and cardiofaciocutaneous syndromes is now better understood given their common molecular background, such that all these syndromes constitute a class of disorders caused by deregulated RAS-MAPK signaling. We report on a novel KRAS gene mutation in a patient presenting the clinical features typical of Costello syndrome and the additional findings seen in Noonan syndrome. This description emphasizes that a subset of patients with Costello syndrome could harbor mutations in other genes involved in the RAS-MAPK signaling.
authors.affiliation: Department of Pediatrics, Instituto da Criança, HC, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 647, Cerqueira César, 05403-900, São Paulo, SP, Brazil. deborarb@icr.hcnet.usp.br.
authors.forename: Débora Romeo
authors.initials: DR
authors.lastname: Bertola
authors.affiliation: Department of Cardiology, Heart Institute (InCor), São Paulo, Brazil.
authors.forename: Alexandre Costa
authors.initials: AC
authors.lastname: Pereira
authors.affiliation: Department of Pediatrics, Instituto da Criança, HC, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 647, Cerqueira César, 05403-900, São Paulo, SP, Brazil.
authors.forename: Amanda Salem
authors.initials: AS
authors.lastname: Brasil
authors.affiliation: Department of Pediatrics, Instituto da Criança, HC, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 647, Cerqueira César, 05403-900, São Paulo, SP, Brazil.
authors.forename: Lilian Maria José
authors.initials: LMJ
authors.lastname: Albano
authors.affiliation: Department of Pediatrics, Instituto da Criança, HC, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 647, Cerqueira César, 05403-900, São Paulo, SP, Brazil.
authors.forename: Chong Ae
authors.initials: CA
authors.lastname: Kim
authors.affiliation: Department of Cardiology, Heart Institute (InCor), São Paulo, Brazil.
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Krieger
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D019465:Craniofacial Abnormalities / Q000235:genetics*; D005260:Female; D011905:Genes, ras; D018740:Genetic Heterogeneity; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D009634:Noonan Syndrome / Q000235:genetics; D013577:Syndrome