Behavioral profile in RASopathies

Paolo Alfieri, Giorgia Piccini, Cristina Caciolo, Francesca Perrino, Maria Luigia Gambardella, Maria Mallardi, Laura Cesarini, Chiara Leoni, Daniela Leone, Chiara Fossati, Angelo Selicorni, Maria Cristina Digilio, Marco Tartaglia, Eugenio Mercuri, Giuseppe Zampino, Stefano Vicari

Research output: Contribution to journalArticlepeer-review


Here, we describe neurobehavioral features in patients with RASopathies (i.e., Noonan syndrome, LEOPARD syndrome, Costello syndrome, and cardiofaciocutaneous syndrome), developmental disorders caused by mutations in genes coding transducers participating in the RAS-MAPK signaling cascade. Parents of 70 individuals with a RASopathy were asked to fill out the following questionnaires: Child Behavior Checklist (CBCL), Social Communication Questionnaire version lifetime (SCQ-L), and Modified Checklist for Autism in toddlers (M-CHAT). Data analysis indicated high rates of internalizing (37%) and externalizing problems (31%) on CBCL. Scores over the cut-off were documented in 64% of patients with cardiofaciocutaneous syndrome, 44% with Costello syndrome, and 12% with Noonan syndrome on SCQ-L/M-CHAT. Our findings indicate that mutations promoting dysregulation of the RAS-MAPK cascade mark an increased psychopathological risk and highlight that autistic-like behavior could be underdiagnosed in patients with RASopathies.

Original languageEnglish
Pages (from-to)934-942
Number of pages9
JournalAmerican Journal of Medical Genetics, Part A
Issue number4
Publication statusPublished - 2014


  • Behavior
  • Cardiofaciocutaneous syndrome
  • Costello syndrome
  • Genotype-phenotype correlation analyses
  • LEOPARD syndrome
  • Noonan syndrome
  • Noonan-like syndrome with loose anagen hair
  • RAS/MAPK cascade

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Medicine(all)


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