Autism spectrum disorder and other neurobehavioural comorbidities in rare disorders of the Ras/MAPK pathway

作者：Garg Shruti; Brooks Ami; Burns Amy; Burkitt Wright Emma; Kerr Bronwyn; Huson Susan; Emsley Richard; Green Jonathan^*

来源：Developmental Medicine and Child Neurology, 2017, 59(5): 544-549.

DOI：10.1111/dmcn.13394

AimTo 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).
MethodFifty 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.
ResultsUsing 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.
InterpretationThis 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.

• 出版日期2017-5