title: Behavioral phenotype in Costello syndrome with atypical mutation: a case report.
abstract: Costello syndrome (CS) is a rare genetic disorder caused, in the majority of cases, by germline missense HRAS mutations affecting Gly(12) promoting enhanced signaling through the MAPK and PI3K-AKT signaling cascades. In general, the cognitive profile in CS is characterized by intellectual disability ranging from mild to severe impairment. The first published descriptions of behavior in CS children underlined the presence of irritability and shyness at younger ages with sociable personality and good empathic skills after 4-5 years of age, however some recent studies have reported autistic traits. We report on a 7-year-old boy heterozygous for a rare duplication of codon 37 (p.E37dup) in HRAS, manifesting impaired social interaction and non-verbal communication and with circumscribed interests. These additional features improve phenotype delineation in individuals with rare HRAS mutations, facilitating the development of specific behavioral treatments which could lead to improvement in cases of autism spectrum disorder.
authors.affiliation: Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Alfieri
authors.forename: Cristina
authors.initials: C
authors.lastname: Caciolo
authors.forename: Giorgia
authors.initials: G
authors.lastname: Piccini
authors.forename: Lidia
authors.initials: L
authors.lastname: D'Elia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Valeri
authors.forename: Deny
authors.initials: D
authors.lastname: Menghini
authors.forename: Marco
authors.initials: M
authors.lastname: Tartaglia
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Digilio
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Stefano
authors.initials: S
authors.lastname: Vicari
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000523:psychology; D002648:Child; D002653:Child Behavior Disorders / Q000235:genetics* / Q000523:psychology; D002659:Child Development Disorders, Pervasive / Q000235:genetics / Q000523:psychology; D056685:Costello Syndrome / Q000235:genetics* / Q000523:psychology*; D006801:Humans; D008297:Male; D009633:Nonverbal Communication / Q000523:psychology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: HRAS; behavior; costello syndrome; genotype; pervasive developmental disorder