Behavioral phenotype in Costello syndrome with atypical mutation: A case report

Research output: Contribution to journalArticle

Abstract

Costello syndrome (CS) is a rare genetic disorder caused, in the majority of cases, by germline missense HRAS mutations affecting Gly12 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.

Original languageEnglish
Pages (from-to)66-71
Number of pages6
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume168
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

Fingerprint

Costello Syndrome
Phenotype
Mutation
Shyness
Inborn Genetic Diseases
Germ-Line Mutation
Missense Mutation
Interpersonal Relations
Phosphatidylinositol 3-Kinases
Codon
Intellectual Disability
Personality
Communication
Therapeutics

Keywords

  • Behavior
  • Costello syndrome
  • Genotype
  • HRAS
  • Pervasive developmental disorder

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

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abstract = "Costello syndrome (CS) is a rare genetic disorder caused, in the majority of cases, by germline missense HRAS mutations affecting Gly12 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.",
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author = "Paolo Alfieri and Cristina Caciolo and Giorgia Piccini and Lidia D'Elia and Giovanni Valeri and Deny Menghini and Marco Tartaglia and Digilio, {Maria Cristina} and Bruno Dallapiccola and Stefano Vicari",
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AU - Alfieri, Paolo

AU - Caciolo, Cristina

AU - Piccini, Giorgia

AU - D'Elia, Lidia

AU - Valeri, Giovanni

AU - Menghini, Deny

AU - Tartaglia, Marco

AU - Digilio, Maria Cristina

AU - Dallapiccola, Bruno

AU - Vicari, Stefano

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N2 - Costello syndrome (CS) is a rare genetic disorder caused, in the majority of cases, by germline missense HRAS mutations affecting Gly12 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.

AB - Costello syndrome (CS) is a rare genetic disorder caused, in the majority of cases, by germline missense HRAS mutations affecting Gly12 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.

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KW - Pervasive developmental disorder

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