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. 2019 Jul;102:208-220.
doi: 10.1016/j.neubiorev.2019.04.022. Epub 2019 May 3.

Genetic Mechanisms of Regression in Autism Spectrum Disorder


Genetic Mechanisms of Regression in Autism Spectrum Disorder

Kristiina Tammimies. Neurosci Biobehav Rev. .


Developmental regression occurs in approximately one-third of children with autism spectrum disorder (ASD). There is a strong genetic influence in ASD and hundreds of genes have been implicated. Theories suggest that regressive ASD is a neurobiological subtype with potentially different causes. This review examines the evidence of genetic influences in regression and provides a summary of its frequency among ASD-associated single-gene disorders. The few twin- and family studies reporting on the concordance of regressive ASD among twin pairs and siblings provide mixed results, and no conclusions of the variance explained by either genetic or environmental factors can be drawn. Among the 89 genes robustly associated with ASD, 16 have been connected to regression, of which seven showed rates of regression higher than 30% among the mutation carriers. The molecular functions of these genes highlight important roles of transcriptional and synapse regulation for regression. Overall, this review shows our limited understanding of factors influencing regressive ASD and calls for additional studies to answer the open questions.

Keywords: CHD2; CHD8; CNTNAP2; Genetic syndrome; KMT5B; MECP2; Regressive autism; SHANK3; SYNGAP1; Twin study.

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