Further evidence of genetic heterogeneity in Costello syndrome: involvement of the KRAS gene.
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.
Bertola
Débora Romeo
DR
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.
Pereira
Alexandre Costa
AC
Department of Cardiology, Heart Institute (InCor), São Paulo, Brazil.
Brasil
Amanda Salem
AS
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.
Albano
Lilian Maria José
LMJ
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.
Kim
Chong Ae
CA
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.
Krieger
José Eduardo
JE
Department of Cardiology, Heart Institute (InCor), São Paulo, Brazil.
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