Longitudinal course of cognitive, adaptive, and behavioral characteristics in Costello syndrome

Am J Med Genet A. 2009 Dec;149A(12):2666-72. doi: 10.1002/ajmg.a.33126.


Costello syndrome is a rare rasopathy caused by germline mutations in the oncogene HRAS resulting in increased signal transduction through the Ras/mitogen-activated protein kinase pathway. In contrast to the more common rasopathies, such as neurofibromatosis type 1 and Noonan syndrome, limited information is available on standardized cognitive testing in this cohort. Past research indicated a mean average IQ in the mild mental retardation range, with strengths in fluid reasoning (FR) and weakness in expressive language, as well as static skills over time. Here we report on standardized IQ and adaptive functioning in 18 individuals with Costello syndrome, nine males and nine females, and longitudinal development for 11 who had previous testing. The overall IQ, ranging from severe mental retardation to the average range, with a mean in the mildly mentally retarded range, was again found to be stable, but an interesting pattern in the development of nonverbal FR was identified. Participants showed an improvement in nonverbal FR, followed by stable skills thereafter, suggesting a "late bloomer" effect in late childhood/early adolescence. Overall adaptive functioning fell into the range of Intellectual Disability for 70% of subjects, with Socialization as a relative strength and Daily Living Skills an area of relative difficulty. Interestingly, females were found to be higher functioning than males in all domains, including Communication, Daily Living Skills and Socialization. Caregivers reported significantly more behavioral concerns in males, including internalizing, externalizing, and other maladaptive behaviors. In contrast, no gender differences were found in cognitive or visuomotor functioning.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptation, Physiological*
  • Adolescent
  • Adult
  • Aging / pathology
  • Behavior / physiology*
  • Child
  • Child, Preschool
  • Cognition / physiology*
  • Cohort Studies
  • Costello Syndrome / genetics
  • Costello Syndrome / physiopathology*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Motor Activity / physiology
  • Mutation / genetics
  • Sex Characteristics
  • Vision, Ocular / physiology
  • Young Adult