Prevalence of autism spectrum disorder phenomenology in genetic disorders: a systematic review and meta-analysis

Richards, Caroline; Jones, Christopher M.; Groves, Laura; Moss, Joanna; Oliver, Chris

doi:10.1016/s2215-0366(15)00376-4

Cited by 325 publications

(311 citation statements)

References 25 publications

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“…Syndromic ASD occurs with Mendelian single gene syndromes, CNV syndromes, and environmental syndromes. Although syndromic ASD has been estimated to account for only 5 to 25 % of all cases of ASD (Adviento et al 2014;de la Torre-Ubieta et al 2016;Jeste and Geschwind 2014), more forms of syndromic ASD continue to be identified (Adviento et al 2014;Richards et al 2015;Roullet et al 2013;Smile et al 2013;Yu and Berry-Kravis 2014;Yuen et al 2015). In addition, syndromic and idiopathic ASD brain impairments have been reported that are similar (Adviento et al 2014;Blackmon 2015;D'Angelo et al 2015;Guilmatre et al 2014;Klusek et al 2015;Sala et al 2015).…”

Section: Does Asd Have Neurobiological Validity?mentioning

confidence: 99%

“…There are many forms of genetic syndromic ASD (Cederlöf et al 2014;Kern et al 2015;Plasschaert et al 2015;Poot 2015;Richards et al 2015). The fact that many different genetic syndromes do yield ASD diagnostic symptoms is the result of locus heterogeneity, wherein different gene variants produce the same phenotype, or the same phenotypic trait or symptom.…”

Section: Genetic Syndromic Asd Has Been Found With Varied Brain Impaimentioning

confidence: 99%

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ASD Validity

Waterhouse

London

Gillberg

2016

Rev J Autism Dev Disord

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ASD research is at an important crossroads. The ASD diagnosis is important for assigning a child to early behavioral intervention and explaining a child's condition. But ASD research has not provided a diagnosis-specific medical treatment, or a consistent early predictor, or a unified life course. If the ASD diagnosis also lacks biological and construct validity, a shift away from studying ASD-defined samples would be warranted. Consequently, this paper reviews recent findings for the neurobiological validity of ASD, the construct validity of ASD diagnostic criteria, and the construct validity of ASD spectrum features. The findings reviewed indicate that the ASD diagnosis lacks biological and construct validity. The paper concludes with proposals for research going forward.Keywords DSM-5 . ASD . Autism . Diagnosis . Validity . Comorbidity . HeterogeneityThe goal of the DSM-3 nosology (American Psychiatric Association 1980) was to create reliable and standard categorical psychiatric diagnoses (Robins and Guze 1970). However, in the past 30 years, clinical, genetics, and neuroscience findings have revealed that the DSM diagnoses are not biologically valid. The National Institutes of Mental Health (NIMH) responded by proposing the Research Domain Criteria (RDoC) framework for a brain-based transdiagnostic psychiatric symptom nosology (Cuthbert and Insel 2013;Insel et al. 2010;Lilienfeld and Treadway 2016). Peterson (2015) and Weinberger et al. (2015) argued that the RDoC could not replace the DSM-5 psychiatric nosology (American Psychiatric Association 2013) or the parallel International Classification of Diseases (ICD) psychiatric nosology (World Health Organization 2012). But BFor the foreseeable future, RDoC is not envisioned as a system of psychiatric classification in its own right. Instead, in the near term, RDoC and DSM-ICD are expected to coexist. Nevertheless, RDoC is intended to provide scaffolding for a large-scale research program that will ultimately yield an alternative to DSM-ICD^ (Lilienfeld and Treadway 2016, p. 445).RDoC advocates accept that DSM-5/ICD psychiatric categories remain necessary in clinical practice, but argue that researchers should shift to RDoC study designs immediately. They assert that studying psychiatric categories lacking biological validity blocks the discovery of brain bases for psychopathology and thus cannot lead to effective medical treatments for specific psychiatric symptoms (Cuthbert and Insel 2013;Insel et al. 2010;Lilienfeld and Treadway 2016;Yee et al. 2015). Against this RDoC imperative for biological validity, Weinberger et al. (2015) countered that current DSM-5 psychiatric behavioral diagnoses were valid when they yielded effective medical treatment, clear prognosis, and a life course specific to a diagnosis.Autism spectrum disorder (ASD) research has been productive (Dawson 2016;de la Torre-Ubieta et al. 2016;Szatmari et al. 2016), but no ASD research findings have met the validity criteria of Weinberger et al. (2015). DSM-5 ASD research has found no s...

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Section: Does Asd Have Neurobiological Validity?mentioning

confidence: 99%

Section: Genetic Syndromic Asd Has Been Found With Varied Brain Impaimentioning

confidence: 99%

ASD Validity

Waterhouse

London

Gillberg

2016

Rev J Autism Dev Disord

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“…Dozens of single genes and chromosomal copy number variants (CNVs)3 increase the relative risk of autism spectrum disorder (ASD) nearly 5–50 times over the current background risk. Yet no single gene or CNV causes ASD in 100% of children who carry the mutation,4 and no single DNA mutation accounts for more than 1–2% of all ASD 5. Specific environmental factors have also been shown to increase the risk of ASD 6, 7.…”

Section: Introductionmentioning

confidence: 99%

Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial

Naviaux

Curtis

et al. 2017

Ann Clin Transl Neurol

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ObjectiveNo drug is yet approved to treat the core symptoms of autism spectrum disorder (ASD). Low‐dose suramin was effective in the maternal immune activation and Fragile X mouse models of ASD. The Suramin Autism Treatment‐1 (SAT‐1) trial was a double‐blind, placebo‐controlled, translational pilot study to examine the safety and activity of low‐dose suramin in children with ASD.MethodsTen male subjects with ASD, ages 5–14 years, were matched by age, IQ, and autism severity into five pairs, then randomized to receive a single, intravenous infusion of suramin (20 mg/kg) or saline. The primary outcomes were ADOS‐2 comparison scores and Expressive One‐Word Picture Vocabulary Test (EOWPVT). Secondary outcomes were the aberrant behavior checklist, autism treatment evaluation checklist, repetitive behavior questionnaire, and clinical global impression questionnaire.ResultsBlood levels of suramin were 12 ± 1.5 μmol/L (mean ± SD) at 2 days and 1.5 ± 0.5 μmol/L after 6 weeks. The terminal half‐life was 14.7 ± 0.7 days. A self‐limited, asymptomatic rash was seen, but there were no serious adverse events. ADOS‐2 comparison scores improved by −1.6 ± 0.55 points (n = 5; 95% CI = −2.3 to −0.9; Cohen's d = 2.9; P = 0.0028) in the suramin group and did not change in the placebo group. EOWPVT scores did not change. Secondary outcomes also showed improvements in language, social interaction, and decreased restricted or repetitive behaviors.InterpretationThe safety and activity of low‐dose suramin showed promise as a novel approach to treatment of ASD in this small study.

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“…2,3 In fact, TSC is one of the most commonly occurring single-gene disorders associated with ASD. [4][5][6] Given the high rate of ASD in TSC and the fact that TSC is often diagnosed in utero or in early infancy, 7 TSC has been considered a model system for understanding mechanisms underlying ASD. [8][9][10][11] However, the specific phenotypic profile of ASD in TSC and the extent to which it converges with nonsyndromic ASD (nsASD) has not been well-established.…”

mentioning

confidence: 99%

Symptom profiles of autism spectrum disorder in tuberous sclerosis complex

Jeste

Varcin²,

Hellemann

et al. 2016

Neurology

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Objective: To determine the extent to which deficits associated with autism spectrum disorder (ASD) in toddlers with tuberous sclerosis complex (TSC) overlap with those in toddlers with nonsyndromic ASD (nsASD) and to examine cognitive function and epilepsy severity in toddlers with TSC and comorbid ASD. This is the endpoint analysis from a longitudinal investigation of ASD risk factors in children with TSC.Methods: Measures included the Autism Diagnostic Observation Schedule (ADOS), the Mullen Scales of Early Learning, and clinical epilepsy variables. A repeated-measures analysis of variance was performed with between-subjects factor of group (typically developing, TSC/no ASD, TSC/ASD, nsASD) and within-subjects factors of individual ADOS item scores in the social communication and repetitive behavior/restricted interest domains. Within the TSC group, comparisons of epilepsy characteristics and cognitive domains were performed using independentsamples t tests. Results:Children with TSC/ASD demonstrated a profile of social communication impairment that had complete convergence with nsASD. Measured social communication impairments included gestures, pointing, eye contact, responsive social smile, and shared enjoyment. This convergence was observed despite the high comorbidity between ASD and cognitive impairment in TSC.Conclusions: This study supports the clinical diagnosis of ASD in young children with TSC and demonstrates remarkable convergence of autism symptoms between TSC/ASD and nsASD. Our results strongly suggest the need for early intervention in toddlers with TSC, with treatment strategies targeting social communication function as well as broader developmental domains, before the onset of autism symptoms. Neurology ® 2016;87:766-772 GLOSSARY ADOS 5 Autism Diagnostic Observation Schedule; ANOVA 5 analysis of variance; ASD 5 autism spectrum disorder; BCH 5 Boston Children's Hospital; DQ 5 developmental quotient; EI 5 early intervention; EL 5 expressive language; EMM 5 estimated marginal mean; FM 5 fine motor; ID 5 intellectual disability; IRB 5 institutional review board; MSEL 5 Mullen Scales of Early Learning; nsASD 5 nonsyndromic autism spectrum disorder; RL 5 receptive language; TD 5 typically developing; TSC 5 tuberous sclerosis complex; UCLA 5 University of California, Los Angeles; VR 5 visual reception.Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder resulting from a TSC1/TSC2 mutation, leading to widespread growth of hamartomas in multiple organ systems, including the brain.1 Children with TSC are at high risk for neuropsychiatric syndromes that include developmental delay, intellectual disability (ID), mood disorders, and autism spectrum disorder (ASD), collectively referred to as TSC-associated neurocognitive deficits. 2,3 In fact, TSC is one of the most commonly occurring single-gene disorders associated with ASD. [4][5][6] Given the high rate of ASD in TSC and the fact that TSC is often diagnosed in utero or in early infancy, 7 TSC has been considered a model s...

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Prevalence of autism spectrum disorder phenomenology in genetic disorders: a systematic review and meta-analysis

Abstract: Cerebra.

Cited by 325 publications

References 25 publications

ASD Validity

ASD Validity

Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial

Symptom profiles of autism spectrum disorder in tuberous sclerosis complex

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