The phenotypic manifestations of rare genic CNVs in autism spectrum disorder.

Significant evidence exists for the association between copy number variants (CNVs) and Autism Spectrum Disorder (ASD); however, most of this work has focused solely on the diagnosis of ASD. There is limited understanding of the impact of CNVs on the 'sub-phenotypes' of ASD. The objective of this paper is to evaluate associations between CNVs in differentially brain expressed (DBE) genes or genes previously implicated in ASD/intellectual disability (ASD/ID) and specific sub-phenotypes of ASD. The sample consisted of 1590 cases of European ancestry from the Autism Genome Project (AGP) with a diagnosis of an ASD and at least one rare CNV impacting any gene and a core set of phenotypic measures, including symptom severity, language impairments, seizures, gait disturbances, intelligence quotient (IQ) and adaptive function, as well as paternal and maternal age. Classification analyses using a non-parametric recursive partitioning method (random forests) were employed to define sets of phenotypic characteristics that best classify the CNV-defined groups. There was substantial variation in the classification accuracy of the two sets of genes. The best variables for classification were verbal IQ for the ASD/ID genes, paternal age at birth for the DBE genes and adaptive function for de novo CNVs. CNVs in the ASD/ID list were primarily associated with communication and language domains, whereas CNVs in DBE genes were related to broader manifestations of adaptive function. To our knowledge, this is the first study to examine the associations between sub-phenotypes and CNVs genome-wide in ASD. This work highlights the importance of examining the diverse sub-phenotypic manifestations of CNVs in ASD, including the specific features, comorbid conditions and clinical correlates of ASD that comprise underlying characteristics of the disorder.

Sleep problems in children and adolescents in an attention deficit hyperactivity disorder service.

OBJECTIVES: Sleep problems are common amongst children and adolescents with attention deficit hyperactivity disorder (ADHD). The purpose of this study was to investigate sleep problems in children and adolescents attending a specialist ADHD service. METHODS: This was a cross-sectional online survey combined with a retrospective chart review, conducted in the ADHD Assessment, Diagnosis, Management, initiation, Research and Education (ADMiRE) service, the first public specialist ADHD service for young people in Ireland. Participants were caregivers of children and adolescents with ADHD attending ADMiRE. Sleep was assessed using The Children's Sleep Habits Questionnaire (CSHQ) and ADHD symptoms were assessed using an abbreviated version of the Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV). Details regarding patient demographics, co-morbidities and medication were collected from patient records. RESULTS: Eighty-four percent of young people scored above the clinical cut-off for a sleep disorder. The most frequently reported sleep problems were related to sleep onset and sleep duration, and 64% of respondents met the criteria for two or more sleep problems. ADHD severity was associated with greater sleep problems. Co-morbid physical, neurodevelopmental, and mental health disorders as well as stimulant use were not associated with greater sleep problems. CONCLUSION: Sleep problems are very common amongst children and adolescents with ADHD. This study has demonstrated an association between more sleep problems and ADHD severity. These findings highlight the need for both effective ADHD treatment to ensure optional sleep in young people as well as effective interventions for sleep problems to prevent worsening of ADHD symptoms.

Neuropsychological presentation of Ganser symptoms.

We describe a patient with memory complaints whose history of head injury, polysubstance abuse and positive neurological findings suggested the presence of dementia. Neuropsychological testing revealed inconsistent performance plus multiple verbal and visuospatial approximate answers leading to the diagnosis of a Ganser episode. This case illustrates the importance of neuropsychological assessment in diagnosing Ganser symptoms and in differentiating this disorder from organic conditions and malingering.