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

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.
Source: Developmental Medicine and Child Neurology - Category: Child Development Authors: Tags: Original Article Source Type: research