Shruti Garg1, Ami Brooks1, Amy Burns1, Emma Burkitt-Wright2, Bronwyn Kerr2, Susan Huson2, Richard Emsley3, Jonathan Green1. 1. Division of Neuroscience & Experimental Psychology, Faculty of Biological, Medical & Health Sciences, University of Manchester and Royal Manchester Children's Hospital and Manchester Academic Health Sciences Centre, Manchester, UK. 2. Manchester Centre for Genomic Medicine, Faculty of Biological, Medical & Health Sciences, University of Manchester and Central Manchester Foundation NHS Trust, Manchester, UK. 3. Centre for Biostatistics, School of Health Sciences, Faculty of Biological, Medical & Health Sciences, University of Manchester, Manchester, UK.
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.
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.
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