The Genetics of Autistic Disorders and its Clinical Relevance: A Review of the Literature

Department of Child and Adolescent Psychiatry, Saarland University Hospital, Homburg, Germany.
Molecular Psychiatry (Impact Factor: 14.5). 02/2007; 12(1):2-22. DOI: 10.1038/
Source: PubMed


Twin and family studies in autistic disorders (AD) have elucidated a high heritability of the narrow and broad phenotype of AD. In this review on the genetics of AD, we will initially delineate the phenotype of AD and discuss aspects of differential diagnosis, which are particularly relevant with regard to the genetics of autism. Cytogenetic and molecular genetic studies will be presented in detail, and the possibly involved aetiopathological pathways will be described. Implications of the different genetic findings for genetic counselling will be mentioned.


Available from: Christine M. Freitag, Sep 24, 2014
    • "The main goal of the current study was to examine whether the cognitive architecture underlying SPX and MPX autism families is different and useful for parsing etiological heterogeneity of ASD. This model of different etiologies in SPX and MPX families is based on evidence from behaviorally-based and genetic research (Sebat et al. 2007; Marshall et al. 2008; Freitag 2007; Virkud et al. 2009; Gerdts et al. 2013). We hypothesized that (a) the different forms of ASD might result in dissimilar cognitive profiles in SPX and MPX ASD probands, and (b) unaffected siblings from MPX but not SPX would display (mild) cognitive deficits compared to controls. "
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    ABSTRACT: Children with an autism spectrum disorder (ASD) and their unaffected siblings from 54 simplex (SPX, one individual in the family affected) and 59 multiplex (MPX, two or more individuals affected) families, and 124 controls were assessed on intelligence, social cognition and executive functions. SPX and MPX ASD probands displayed similar cognitive profiles, but within-family contrasts were highest in SPX families, suggesting SPX-MPX stratification may help parse etiological heterogeneity of ASD. Unaffected siblings (regardless SPX or MPX) were mostly unimpaired, suggesting that cognitive problems may be part of the defining features of ASD, rather than being an endophenotypic trait. Except for affective prosody, which appeared to be the most sensitive cognitive marker for detecting familial risk for ASD.
    Journal of Autism and Developmental Disorders 09/2015; DOI:10.1007/s10803-015-2572-9 · 3.06 Impact Factor
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    • "Autism is a severe, life-long developmental disorder that compromises functioning across multiple domains including social behavior, language, sensory function, and ritualistic/repetitive behaviors and interests. While the etiology of autism is complex and not fully understood, strong evidence from twin and family studies suggests a large genetic contribution (Freitag, 2007; Gupta & State, 2007). Iron deficiency (ID) is the most common and persevering nutritional disorder and continues to be an important public health problem worldwide (WHO, 2007). "
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    ABSTRACT: Iron has an important role in cognitive, behavioral, and motor development. A high prevalence of iron deficiency (ID) has been reported in people with autism. Children with autism are at risk for ID and this condition may increase the severity of psychomotor and behavioral problems, some of which already inherently exist in these children. Aim of the study: The aim of this study is to investigate the association between autism and iron deficiency in autistic children in the Northern West Bank and to identify food selectivity and compare indices of food selectivity among children with autism, children with mental disorders and typically developing children (normal children).Background: Autism is a developmental disorder characterized by qualitative abnormalities of social interaction, impairments in communication, and unusual forms of repetitive behavior . Research shows that a high prevalence of iron deficiency has been reported in children with autism spectrum disorders. Inadequate dietary iron intake was considered as a cause of iron deficiency, and low iron intake was thought to be associated with food selectivity which is commonly seen in children with autistic disorders. Method: 90 children with an age range of 3 to 13 years participated in a case control study distributed into study group and two control groups. Thirty children diagnosed with autism according to DSMIV and ICD-10 criteria served as a study group, 30 children with mental disorders other than autism served as a control group, and 30 typically developing children taken from the public functioned as a second control group. The three groups were matched for age, gender and geographical area. Serum ferritin, hemoglobin, hematocrit, mean corpuscular volume, and red cell distribution width values were measured and analyzed with food habit survey and demographic data. Results: ID was detected in 20% (N = 6/30) of autistic children based on Serum ferritin level (SF< 10µ/l), compared with 0% for the two control groups (p= 0.0001). Anemia was defined as hemoglobin <110g/l for children under the age of 6 years and hemoglobin <120g/l for children between 6 and 13 years of age .When analysis done for HGB to these six children (children who have low serum ferritin); it was found that 66.6% (4/6) of the children two were pre-school male children (HGB is less than 110g/1), and the other two were one male and one female of school children (HGB is less than 120g/l) have iron deficiency anemia, and the iron deficiency anemia was 13.3% (4\30) for all autistic group. The results indicated that these differences were for males. It was found also that the frequency of low iron intake in these children was associated with feeding difficulties and food selectivity; there was a significant difference between children in the autistic group who chose foods with a red color as a favorite 23% (7/30) compared to the other two control groups: 0%, respectively (p= 0.0001). The results demonstrated also a significant difference in the frequency of snacks per day (≥ 4) in autistic children 40% (12/30) compared to both mental disorder 16.7 % (n = 5/30) (p = 0.006) and typically developing children 6.7% (n = 2/30) groups (p = 0.001).Conclusions: Results of this study indicated that there is an association between autism, iron deficiency and anemia. Low levels of serum ferritin in autistic children might be a sign of iron deficiency and an early precursor of iron deficiency anemia. These findings suggest that food selectivity is more common in children with autism than in typically developing children. These findings suggest that ferritin levels should be measured in children with autism as a part of routine investigation
    Critical Public Health 01/2015; 16(2422-8419). · 0.88 Impact Factor
    • "A variety of neurodevelopmental disorders affect im - portant features of human cognition and behavior . The processes underlying pathological variation are often complex and involve diverse genetic mechanisms , as is the case in schizophrenia [ Eisenberg and Berman , 2010 ] and ASD [ Freitag , 2007 ] , which seem to involve a high rate of de novo mutations [ Sebat et al . , 2007 ; Sanders et al . "
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    ABSTRACT: The evolution of the human brain has been marked by a nearly 3-fold increase in size since our divergence from the last common ancestor shared with chimpanzees and bonobos. Despite increased interest in comparative neuroanatomy and phylogenetic methods, relatively little is known regarding the effects that this enlargement has had on its internal organization, and how certain areas of the brain have differentially expanded over evolutionary time. Analyses of the microstructure of several regions of the human cortex and subcortical structures have demonstrated subtle changes at the cellular and molecular level, suggesting that the human brain is more than simply a 'scaled-up' primate brain. Ongoing research in comparative neuroanatomy has much to offer regarding our understanding of human brain evolution. Through analysis of the neuroanatomical phenotype at the level of reorganization in cytoarchitecture and cellular morphology, new data continue to highlight changes in cell density and organization associated with volumetric changes in discrete regions. An understanding of the functional significance of variation in neural circuitry can further be approached through studies of atypical human development. Many neurodevelopmental disorders cause disruption in systems associated with uniquely human features of cognition, including language and social cognition. Understanding the genetic and developmental mechanisms that underlie variation in the human cognitive phenotype can help to clarify the functional significance of interspecific variation. By uniting approaches from comparative neuroanatomy and neuropathology, insights can be gained that clarify trends in human evolution. Here, we explore these lines of evidence and their significance for understanding functional variation between species as well as within neuropathological variation in the human brain. © 2014 S. Karger AG, Basel.
    Brain Behavior and Evolution 09/2014; 84(2):135-155. DOI:10.1159/000365409 · 2.01 Impact Factor
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