Autism traits in the RASopathies

Brigid Adviento, Iris L. Corbin, Felicia Widjaja, Guillaume Desachy, Nicole Enrique, Tena Rosser, Susan Risi, Elysa J. Marco, Robert L. Hendren, Carrie E. Bearden, Katherine A Rauen, Lauren A. Weiss

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Background 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. Methods We examined the association of autism traitswith 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). Results 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. Conclusions 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.

Original languageEnglish (US)
Pages (from-to)10-20
Number of pages11
JournalJournal of Medical Genetics
Volume51
Issue number1
DOIs
StatePublished - 2014
Externally publishedYes

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Autistic Disorder
Siblings
Mitogen-Activated Protein Kinases
Neurofibromatosis 1
Costello Syndrome
Sexism
Population
Communication
Mutation
Genes
Autism Spectrum Disorder

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Adviento, B., Corbin, I. L., Widjaja, F., Desachy, G., Enrique, N., Rosser, T., ... Weiss, L. A. (2014). Autism traits in the RASopathies. Journal of Medical Genetics, 51(1), 10-20. https://doi.org/10.1136/jmedgenet-2013-101951

Autism traits in the RASopathies. / Adviento, Brigid; 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.

In: Journal of Medical Genetics, Vol. 51, No. 1, 2014, p. 10-20.

Research output: Contribution to journalArticle

Adviento, B, Corbin, IL, Widjaja, F, Desachy, G, Enrique, N, Rosser, T, Risi, S, Marco, EJ, Hendren, RL, Bearden, CE, Rauen, KA & Weiss, LA 2014, 'Autism traits in the RASopathies', Journal of Medical Genetics, vol. 51, no. 1, pp. 10-20. https://doi.org/10.1136/jmedgenet-2013-101951
Adviento B, Corbin IL, Widjaja F, Desachy G, Enrique N, Rosser T et al. Autism traits in the RASopathies. Journal of Medical Genetics. 2014;51(1):10-20. https://doi.org/10.1136/jmedgenet-2013-101951
Adviento, Brigid ; 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. / Autism traits in the RASopathies. In: Journal of Medical Genetics. 2014 ; Vol. 51, No. 1. pp. 10-20.
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abstract = "Background 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. Methods We examined the association of autism traitswith 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). Results 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. Conclusions 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.",
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AU - Desachy, Guillaume

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AU - Rosser, Tena

AU - Risi, Susan

AU - Marco, Elysa J.

AU - Hendren, Robert L.

AU - Bearden, Carrie E.

AU - Rauen, Katherine A

AU - Weiss, Lauren A.

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N2 - Background 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. Methods We examined the association of autism traitswith 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). Results 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. Conclusions 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.

AB - Background 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. Methods We examined the association of autism traitswith 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). Results 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. Conclusions 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.

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