Characteristics and Concordance of Autism Spectrum Disorders Among 277 Twin Pairs

Department of Medical Informatics, Kennedy Krieger Institute, Baltimore, MD 21211, USA.
JAMA Pediatrics (Impact Factor: 5.73). 10/2009; 163(10):907-14. DOI: 10.1001/archpediatrics.2009.98
Source: PubMed


To examine patterns of autism spectrum disorder (ASD) inheritance and other features in twin pairs by zygosity, sex, and specific ASD diagnosis.
Cross-sectional study.
Internet-based autism registry for US residents.
Survey results from 277 twin pairs (210 dizygotic [DZ] and 67 monozygotic [MZ]) aged 18 years or younger with at least 1 affected twin.
Zygosity and sex.
Concordance within twin pairs of diagnosis, natural history, and results from standardized autism screening.
Pairwise ASD concordance was 31% for DZ and 88% for MZ twins. Female and male MZ twins were 100% and 86% concordant, respectively, and DZ twin pairs with at least 1 female were less likely to be concordant (20%) than were male-male DZ twin pairs (40%). The hazard ratio for ASD diagnosis of the second twin after a first-twin diagnosis was 7.48 for MZ vs DZ twins (95% confidence interval, 3.8-14.7). Affected DZ individual twins had an earlier age at first parental concern and more frequent diagnoses of intellectual disability than did MZ twins; MZ twins had a higher prevalence of bipolar disorder and Asperger syndrome and higher concordance of the latter. Results of autism screening correlated with parent-reported ASD status in more than 90% of cases.
Our data support greater ASD concordance in MZ vs DZ twins. Overall higher functioning, psychiatric comorbidity, and Asperger syndrome concordance among affected MZ vs DZ twins may also suggest differential heritability for different ASDs. For families in which one MZ twin is diagnosed with ASD, the second twin is unlikely to receive an ASD diagnosis after 12 months. In addition, Internet parent report of ASD status is valid.

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Available from: Rebecca E Rosenberg, Oct 15, 2015
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    • "The wide range of phenotypical traits regarding comorbidities and various degrees of cognitive and language impairments makes up the " spectrum " and adds complexity to the determination of genetic markers associated with a distinct phenotype [2]. ASDs have a strong genetic component as ascertained by a 90% concordance among monozygotic twins [3]. Significant advancements have been made in identifying molecular mechanisms involved in ASDs by studying disorders with Mendelian inheritance patterns such as Tuberous Sclerosis complex (TSC1 and TSC2), Rett syndrome (MECP2), Fragile X syndrome (FXS; which results from mutated Fragile X mental retardation-1, FMR1), and Cowden syndrome (PTEN), but, altogether, these disorders do not account for more than 10% of cases [4]. "
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    ABSTRACT: Hundreds of genes have been associated with autism spectrum disorders (ASDs) and the interaction of weak and de novo variants derive from distinct autistic phenotypes thus making up the “spectrum.” The convergence of these variants in networks of genes associated with synaptic function warrants the study of cell signaling pathways involved in the regulation of the synapse. The Wnt/ β -catenin signaling pathway plays a central role in the development and regulation of the central nervous system and several genes belonging to the cascade have been genetically associated with ASDs. In the present paper, we review basic information regarding the role of Wnt/ β -catenin signaling in excitatory/inhibitory balance (E/I balance) through the regulation of pre- and postsynaptic compartments. Furthermore, we integrate information supporting the role of the glycogen synthase kinase 3 β (GSK3 β ) in the onset/development of ASDs through direct modulation of Wnt/ β -catenin signaling. Finally, given GSK3 β activity as key modulator of synaptic plasticity, we explore the potential of this kinase as a therapeutic target for ASD.
    Full-text · Article · Jan 2016
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    • "This is because the primary differences between MZ and DZ twins, aside from nonshared factors (e.g., experiences outside the home, friends, etc.), are genetically mediated. Twin studies to date yield heritability estimates of ASD between 70 and 80% [27] [28] [29]. Aside from one recent study suggesting a significant contribution of shared environmental factors to ASD (experiences that are common to both twins, e.g., socioeconomic status and parental mental health problems [4]), these studies have generally reported small or nonsignificant shared environmental effects. "
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    ABSTRACT: Neurodevelopmental disorders represent a broad class of childhood neurological conditions that have a significant bearing on the wellbeing of children, families, and communities. In this review, we draw on evidence from two common and widely studied neurodevelopmental disorders-autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD)-to demonstrate the utility of genetically informed sibling designs in uncovering the nature and pathogenesis of these conditions. Specifically, we examine how twin, recurrence risk, and infant prospective tracking studies have contributed to our understanding of genetic and environmental liabilities towards neurodevelopmental morbidity through their impact on neurocognitive processes and structural/functional neuroanatomy. It is suggested that the siblings of children with ASD and ADHD are at risk not only of clinically elevated problems in these areas, but also of subthreshold symptoms and/or subtle impairments in various neurocognitive skills and other domains of psychosocial health. Finally, we close with a discussion on the practical relevance of sibling designs and how these might be used in the service of early screening, prevention, and intervention efforts that aim to alleviate the negative downstream consequences associated with disorders of neurodevelopment.
    Full-text · Article · Aug 2015 · BioMed Research International
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    • "There is sufficient research from twin and family studies demonstrating the involvement of genes in ASDs (Guo et al., 2011; Frazier et al., 2014). However, the most recent evidence suggests that in monozygotic twins (MTs) that share the same genetic material, the concordance rates range from 43 to 88% (Rosenberg et al., 2009; Lichtenstein et al., 2010; Stilp et al., 2010; Hallmayer et al., 2011; Ronald & Hoekstra, 2014). Additionally, MTs that are diagnosed with ASDs often display different subsets of autism symptoms (Kates et al., 1998, 2004; Belmonte & Carper, 2006; Mitchell et al., 2009). "
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    ABSTRACT: The prevalence of Autism Spectrum Disorders (ASDs) has been on the rise over recent years. The presence of diverse subsets of candidate genes in each individual with an ASD and the vast variability of phenotypical differences suggest that the interference of an exogenous environmental component may greatly contribute to the development of ASDs. The lipid mediator prostaglandin E2 (PGE2 ) is released from phospholipids of cell membranes and is important in brain development and function; PGE2 is involved in differentiation, synaptic plasticity, and calcium regulation. Our previous review already described extrinsic factors including deficient dietary supplementation and exposure to oxidative stress, infections, and inflammation that can disrupt signalling of the PGE2 pathway and contribute to ASDs. In this review, we describe the structure and establishment of two key protective barriers for the brain during early development: the blood brain barrier and the placental barrier. We then provide the first comprehensive summary of other environmental factors-such as exposure to chemicals in air pollution, pesticides, and consumer products-that can also disturb PGE2 signalling and increase the risk for developing ASDs. We also describe how these exogenous agents are capable of crossing the protective barriers of the brain during critical developmental periods when barrier components are still being formed. This review underlines the importance of avoiding or limiting exposure to these factors during vulnerable periods in development. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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