The Genetics of Autism Spectrum Disorders – A Guide for Clinicians

Faculty of Medicine, University of Heidelberg, Im Neuenheimer Feld 134b, 69120, Heidelberg, Germany, .
Current Psychiatry Reports (Impact Factor: 3.24). 01/2013; 15(1):334. DOI: 10.1007/s11920-012-0334-3
Source: PubMed

ABSTRACT Recent advances in genetic testing technology have made chromosome microarray analysis (CMA) a first-tier clinical diagnostic test for Autism Spectrum Disorders (ASDs). Two main types of microarrays are available, single nucleotide polymorphism (SNP) arrays and array comparative genomic hybridization (aCGH), each with its own advantages and disadvantages in ASDs testing. Rare genetic variants, and copy number variants (CNVs) in particular, have been shown to play a major role in ASDs. More than 200 autism susceptibility genes have been identified to date, and complex patterns of inheritance, such as oligogenic heterozygosity, appear to contribute to the etiopathogenesis of ASDs. Incomplete penetrance and variable expressivity represent particular challenges in the interpretation of CMA testing of autistic individuals. This review aims to provide an overview of autism genetics for the practicing physician and gives hands-on advice on how to follow-up on abnormal CMA findings in individuals with neuropsychiatric disorders.

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    • "The most consistently reported single-gene disorders associated with ASD (*5% of cases) are Fragile X syndrome, Rett syndrome, tuberous sclerosis, and phosphatase and tensin homolog (PTEN) mutations (Carter and Scherer 2013). Rare genetic variants , and copy number variants in particular, have been shown to play a major role in ASD (Heil and Schaaf 2013). In addition to autism-related genes, various environmental events are thought to act as triggering factors in the development of ASD, including obstetric complications (Arndt et al. 2005; Libbey et al. 2005; Patterson 2009); prenatal influenza, rubella, and cytomegalovirus infections (Pardo et al. 2005); maternal stress during pregnancy (Beversdorf et al. 2005; but also see Rai et al. 2012); and maternal use of thalidomide (Strömland et al. 1994), misoprostol, and especially valproic acid during pregnancy (Landrigan 2010; Christensen et al. 2013). "
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    ABSTRACT: Objective: Little is known about the effectiveness of pharmacological interventions on autism spectrum disorder (ASD). This is a systematic review of the randomized controlled trials (RCTs) of oxytocin interventions in autism, made from January 1990 to September 2013. Method: A search of computerized databases was supplemented by manual search in the bibliographies of key publications. The methodological quality of the studies included in the review was evaluated independently by two researchers, according to a set of formal criteria. Discrepancies in scoring were resolved through discussion. Results: The review yielded seven RCTs, including 101 subjects with ASD (males=95) and 8 males with Fragile X syndrome. The main categories of target symptoms tested in the studies were repetitive behaviors, eye gaze, and emotion recognition. The studies had a medium to high risk of bias. Most studies had small samples (median=15). All the studies but one reported statistically significant between-group differences on at least one outcome variable. Most findings were characterized by medium effect size. Only one study had evidence that the improvement in emotion recognition was maintained after 6 weeks of treatment with intranasal oxytocin. Overall, oxytocin was well tolerated and side effects, when present, were generally rated as mild; however, restlessness, increased irritability, and increased energy occurred more often under oxytocin. Conclusions: RCTs of oxytocin interventions in autism yielded potentially promising findings in measures of emotion recognition and eye gaze, which are impaired early in the course of the ASD condition and might disrupt social skills learning in developing children. There is a need for larger, more methodologically rigorous RCTs in this area. Future studies should be better powered to estimate outcomes with medium to low effect size, and should try to enroll female participants, who were rarely considered in previous studies. Risk of bias should be minimized. Human long-term administration studies are necessary before clinical recommendations can be made.
    Journal of child and adolescent psychopharmacology 03/2014; 24(2):54-68. DOI:10.1089/cap.2013.0040 · 2.93 Impact Factor
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    ABSTRACT: Autism spectrum disorders (ASD) encompass a range of neurodevelopmental conditions that are clinically and etiologically very heterogeneous. ASD is currently diagnosed entirely on behavioral criteria, but intensive research efforts are focused on identifying biological markers for disease risk and early diagnosis. Here, we discuss recent progress toward identifying biological markers for ASD and highlight specific challenges as well as ethical aspects of translating ASD biomarker research into the clinic.
    Disease markers 07/2013; 35(1):55-65. DOI:10.1155/2013/476276 · 1.56 Impact Factor
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    ABSTRACT: DSM-5 has moved autism from the level of subgroups ("apples and oranges") to the prototypical level ("fruit"). But making progress in research, and ultimately improving clinical practice, will require identifying subgroups within the autism spectrum.
    PLoS Biology 04/2013; 11(4):e1001544. DOI:10.1371/journal.pbio.1001544 · 9.34 Impact Factor
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