Autism spectrum disorder and other neurobehavioural comorbidities in rare disorders of the Ras/MAPK pathway. (4th February 2017)

• Record Type: Journal Article
• Authors: Garg, Shruti; Brooks, Ami; Burns, Amy; Burkitt‐Wright, Emma; Kerr, Bronwyn; Huson, Susan; Emsley, Richard; Green, Jonathan
• Is Part Of: Developmental medicine & child neurology. Volume 59:Number 5(2017)
• Page Start: 544
• Page End: 549
• Publication Date: 2017-02-04
• Subjects: Child development -- Periodicals; Pediatric neurology -- Periodicals; 616.8
• DOI: 10.1111/dmcn.13394
• Languages: English
• ISSNs: 0012-1622

Abstract

Abstract : Aim: To investigate the cognitive and behavioural phenotype in rare disorders of the Ras/MAPK pathway, namely Noonan, cardiofaciocutaneous (CFC), and Costello syndromes, particularly prevalence of autism spectrum disorder (ASD) and attention‐deficit–hyperactivity disorder (ADHD). Method: Fifty children were recruited over 10 months through the regional genetics service and advertisements. A range of parent, child, and observational measures were administered including Autism Diagnostic Interview‐Revised and Autism Diagnostic Observation Scale. Results: Using the Collaborative Programme for Excellence in Autism criteria, 12 out of 40 children with Noonan syndrome (30%) showed ASD, and 12 out of 40 (30%) with partial ASD features and 16 out of 40 (40%) showed non‐ASD. The Noonan syndrome ASD group showed male dominance in a ratio of 5:1. In the CFC group, eight out of nine children met the criteria for ASD, with equal sex distribution. Additionally 19 out of 40 (48%) of the Noonan syndrome group and eight out of nine (88.9%) of the CFC group scored met clinical criteria for ADHD. Only one child was in the Costello syndrome group. Interpretation: This is the first systematic study to suggest a high prevalence of ASD in Noonan and CFC syndromes, and thus offers crucial evidence to support the importance of the Ras/MAPK pathway in the aetiology of ASD. Limitations include the inevitable possibility of a sampling bias in a rare disorder study of this kind. What this paper adds: Both autism spectrum disorder and attention‐deficit–hyperactivity disorder are highly prevalent in the RASopathies. This article is commented on by Sznajer on page461 of this issue.