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PMID: 24101678 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Autism traits in the RASopathies.

Journal of medical genetics ·Vol. 51 ·No. 1 ·2014-01-00 ·Pages 10-20

Adviento B, Corbin IL, Widjaja F, Desachy G, Enrique N, Rosser T, Risi S, Marco EJ, Hendren RL, Bearden CE, Rauen KA, Weiss LA

Abstract

Mutations in Ras/mitogen-activated protein kinase (Ras/MAPK) pathway genes lead to a class of disorders known as RASopathies, including neurofibromatosis type 1 (NF1), Noonan syndrome (NS), Costello syndrome (CS), and cardio-facio-cutaneous syndrome (CFC). Previous work has suggested potential genetic and phenotypic overlap between dysregulation of Ras/MAPK signalling and autism spectrum disorders (ASD). Although the literature offers conflicting evidence for association of NF1 and autism, there has been no systematic evaluation of autism traits in the RASopathies as a class to support a role for germline Ras/MAPK activation in ASDs. We examined the association of autism traits with NF1, NS, CS and CFC, comparing affected probands with unaffected sibling controls and subjects with idiopathic ASDs using the qualitative Social Communication Questionnaire (SCQ) and the quantitative Social Responsiveness Scale (SRS). Each of the four major RASopathies showed evidence for increased qualitative and quantitative autism traits compared with sibling controls. Further, each RASopathy exhibited a distinct distribution of quantitative social impairment. Levels of social responsiveness show some evidence of correlation between sibling pairs, and autism-like impairment showed a male bias similar to idiopathic ASDs. Higher prevalence and severity of autism traits in RASopathies compared to unaffected siblings suggests that dysregulation of Ras/MAPK signalling during development may be implicated in ASD risk. Evidence for sex bias and potential sibling correlation suggests that autism traits in the RASopathies share characteristics with autism traits in the general population and clinical ASD population and can shed light on idiopathic ASDs.

Keywords
Autism Costello Syndrome Cranio-Facio-Cutaneous Syndrome Neurofibromatosis Type 1 Noonan Syndrome
MeSH Terms
Adolescent Adult Autistic Disorder/diagnosis,genetics Child Costello Syndrome/diagnosis,genetics Diagnosis, Differential Ectodermal Dysplasia/diagnosis,genetics Facies Failure to Thrive/diagnosis,genetics Female Heart Defects, Congenital/diagnosis,genetics Humans Male Middle Aged Mitogen-Activated Protein Kinases/metabolism Mutation Neuropsychological Tests Noonan Syndrome/diagnosis,genetics Patient Outcome Assessment Phenotype Prevalence Quantitative Trait, Heritable Sex Factors Siblings Signal Transduction Surveys and Questionnaires Young Adult ras Proteins/genetics,metabolism
Chemicals
Mitogen-Activated Protein Kinases ras Proteins
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Adviento Brigid
Department of Psychiatry, University of California San Francisco, San Francisco, California, USA.
Corbin Iris L
Widjaja Felicia
Desachy Guillaume
Enrique Nicole
Rosser Tena
Risi Susan
Marco Elysa J
Hendren Robert L
Bearden Carrie E
Rauen Katherine A
Weiss Lauren A
Supplementary Concepts
Cardiofaciocutaneous syndrome (Disease)
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Article Info
Journal
Journal of medical genetics
Abbr.
J Med Genet
ISSN
1468-6244
DOI
10.1136/jmedgenet-2013-101951
Published
2014-01-00
Epub
2013-00-07
Pages
10-20
Language
English
Region
England
NLM ID
2985087R
PMCID
PMC4230531
Subset
IM
Grants
NIH HHS · 1DP2OD007449 · United States
NIH HHS · DP2 OD007449 · United States
NIMH NIH HHS · R34 MH089299 · United States
NIMH NIH HHS · R34 MH089299-01 · United States
NIAMS NIH HHS · R01 AR062165 · United States
External Links
PubMed source DOI: 10.1136/jmedgenet-2013-101951 PMC Full Text View journal details
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