The Assessment and Presentation of Autism Spectrum Disorder and Associated Characteristics in Individuals with Severe Intellectual Disability and Genetic Syndromes

Moss, Joanna; Howlin, Patricia; Oliver, Chris

doi:10.1093/oxfordhb/9780195305012.013.0018

Cited by 21 publications

(26 citation statements)

References 159 publications

(135 reference statements)

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“…Our data support findings from studies of subjects with genetic disorders (Moss et al, 2011) and individuals with intellectual disability (de Bildt et al, 2004) that cognitive impairments can confound the assessment for autism symptoms. In particular, we observed that lower cognitive functioning was associated with higher ADI-R social and communication domain scores, and after adjustment for cognitive functioning, there were no significant differences between BDNF+/− and BDNF+/+ subjects for any ADI-R domain.…”

Section: Discussionsupporting

confidence: 83%

Association of brain-derived neurotrophic factor (BDNF) haploinsufficiency with lower adaptive behaviour and reduced cognitive functioning in WAGR/11p13 deletion syndrome

Han

Thurm

Williams

et al. 2013

Cortex

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In animal studies, brain-derived neurotrophic factor (BDNF) is an important regulator of central nervous system development and synaptic plasticity. WAGR (Wilms tumour, Aniridia, Genitourinary anomalies, and mental Retardation) syndrome is caused by 11p13 deletions of variable size near the BDNF locus and can serve as a model for studying human BDNF haploinsufficiency (+/−). We hypothesized that BDNF+/− would be associated with more severe cognitive impairment in subjects with WAGR syndrome. Twenty-eight subjects with WAGR syndrome (6–28y), 12 subjects with isolated aniridia due to PAX6 mutations/microdeletions (7–54y), and 20 healthy controls (4–32y) received neurocognitive assessments. Deletion boundaries for the subjects in the WAGR group were determined by high resolution oligonucleotide array comparative genomic hybridization. Within the WAGR group, BDNF+/− subjects (n=15), compared with BDNF intact (+/+) subjects (n=13), had lower adaptive behaviour (p=.02), reduced cognitive functioning (p=.04), higher levels of reported historical (p=.02) and current (p=.02) social impairment, and higher percentage meeting cut-off score for autism (p=.047) on Autism Diagnostic Interview-Revised. These differences remained nominally significant after adjusting for visual acuity. Using diagnostic measures and clinical judgment, 3 subjects (2 BDNF+/− and 1 BDNF+/+) in the WAGR group (10.7%) were classified with autism spectrum disorder. A comparison group of visually impaired subjects with isolated aniridia had cognitive functioning comparable to that of healthy controls. In summary, among subjects with WAGR syndrome, BDNF+/− subjects had a mean Vineland Adaptive Behaviour Compose score that was 14 points lower and a mean IQ that was 20 points lower than BDNF+/+ subjects. Our findings support the hypothesis that BDNF plays an important role in human neurocognitive development.

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Section: Discussionsupporting

confidence: 83%

Association of brain-derived neurotrophic factor (BDNF) haploinsufficiency with lower adaptive behaviour and reduced cognitive functioning in WAGR/11p13 deletion syndrome

Han

Thurm

Williams

et al. 2013

Cortex

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“…The recommendation not to use genetic testing as part of routine diagnosis is based on current evidence, as the causal association between ASD and genetic disorders remains uncertain (Moss et al, 2011). Whilst neurological and genetic differences in ASD are increasingly well studied (Jordan and Murphy, 2011;Geschwind, 2011) current research has yet to be usefully applied to clinical practice.…”

Section: Genetic Testingmentioning

confidence: 99%

The NICE guideline on recognition, referral, diagnosis and management of adults on the autism spectrum

Wilson

Roberts

Gillan

et al. 2013

Advances in Mental Health and Intellectual Disabilities

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Purpose -This paper aims to provide an overview of the recent National Institute for Health and Clinical Excellence (NICE) clinical guidance for diagnosis and treatment of adults with Autism Spectrum Disorder (ASD) and to discuss clinical and practical implications. Design/methodology/approach -This is a summary and discussion of the NICE guidance for adults with autism. This includes discussion of relevant related guidance, the need for transition services for young people with ASD, education of professionals, applicability of the guidance to people with intellectual disabilities and challenges related to implementation of the guidance in a changing National Health Service. Findings -The guidance provides an excellent overview of current and state-of-the-art strategies for diagnosis and treatment of ASD-related behaviours, and their level of evidence. In terms of diagnosis, the main recommendation for clinicians is to carry out a comprehensive assessment for adults with suspected autism, taking into account co-morbid mental health problems and potential unmet needs. In addition, NICE makes recommendations regarding pharmacological and psychological interventions and these are discussed. The guidance also makes specific recommendations regarding service design, for example the formation of Autism Strategy Groups. This will hopefully support the development of specialist adult autism services. Originality/value -This paper provides new insights into the implications of the recently published NICE clinical guidance for autism in adults, relevant for health care professionals, service managers and service users.

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“…Previous comparisons of individuals with ASD with or without an associated syndrome (or a de novo mutation of potential pathogenic significance) are limited by the difficulty of identifying appropriate controls with idiopathic ASD (10). Individuals with neurogenetic syndromes with ASD often have significantly lower cognitive abilities than those with only ASD or only the neurogenetic syndrome, making it difficult to interpret direct comparisons on behavioral measures (13). Because ASD symptom measures are strongly influenced by IQ, comparing ASD severity across cognitive ability is particularly problematic (14).…”

Section: Introductionmentioning

confidence: 99%

Identification of Developmental and Behavioral Markers Associated With Genetic Abnormalities in Autism Spectrum Disorder

Bishop

Farmer

Bal

et al. 2017

AJP

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Objective Aside from features associated with risk of neurogenetic syndromes in general (e.g., cognitive impairment), limited progress has been made in identifying phenotype-genotype relationships in autism spectrum disorder (ASD). Method This study extends work in the Simons Simplex Collection (SSC) by comparing the phenotypic profiles of ASD probands with or without identified de novo loss of function mutations (LoF) or Copy Number Variants (CNV) in high confidence ASD-associated genes/loci (Sanders et al., 2015). Analyses pre-emptively accounted for documented differences in sex and IQ in affected individuals with de novo mutations, by matching probands with and without these genetic events on sex, IQ, and age before comparing them on multiple behavioral domains. Results Children with de novo mutations (n=112) showed greater likelihood of motor delays during early development (i.e., later age of walking), but less impairment in certain measures of ASD core symptoms (parent-rated social-communication impairment and clinician-rated diagnostic certainty) in later childhood. These children also showed relative strengths in verbal and language abilities, including a smaller discrepancy between nonverbal and verbal IQ and a greater likelihood of having achieved fluent language. Conclusions Children with ASD with de novo mutations may exhibit a “muted” symptom profile with respect to social-communication and language deficits, relative to those with ASD with no identified genetic abnormalities. Such findings suggest that examining early milestone differences and standardized testing results may be helpful in etiologic efforts, and potentially in clinical differentiation of various subtypes of ASD, but only if developmental/demographic variables are properly accounted for first.

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The Assessment and Presentation of Autism Spectrum Disorder and Associated Characteristics in Individuals with Severe Intellectual Disability and Genetic Syndromes

Cited by 21 publications

References 159 publications

Association of brain-derived neurotrophic factor (BDNF) haploinsufficiency with lower adaptive behaviour and reduced cognitive functioning in WAGR/11p13 deletion syndrome

Association of brain-derived neurotrophic factor (BDNF) haploinsufficiency with lower adaptive behaviour and reduced cognitive functioning in WAGR/11p13 deletion syndrome

The NICE guideline on recognition, referral, diagnosis and management of adults on the autism spectrum

Identification of Developmental and Behavioral Markers Associated With Genetic Abnormalities in Autism Spectrum Disorder

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