Le Journal of Child Neurology consacre son numéro de décembre 2015 à l’actualité et aux perspectives de recherches sur l’autisme.

1. Maria BL. Autism Spectrum Disorders : Current Understanding and Future Directions. Journal of child neurology. 2015 December 1, 2015 ;30(14):1859-60.

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2. Harony-Nicolas H, De Rubeis S, Kolevzon A, Buxbaum JD. Phelan McDermid Syndrome : From Genetic Discoveries to Animal Models and Treatment. Journal of child neurology. 2015 December 1, 2015 ;30(14):1861-70.

Phelan-McDermid syndrome or 22q13.3 deletion syndrome is a rare neurodevelopmental disorder characterized by generalized developmental delay, intellectual disability, absent or delayed speech, seizures, autism spectrum disorder, neonatal hypotonia, physical dysmorphic features, and recurrent medical comorbidities. Individuals with Phelan-McDermid syndrome have terminal deletions of the chromosomal region 22q13.3 encompassing SHANK3, a gene encoding a structural component of excitatory synapses indispensable for proper synaptogenesis and neuronal physiology, or point mutations within the gene. Here, we review the clinical aspects of the syndrome and the genetic findings shedding light onto the underlying etiology. We also provide an overview on the evidence from genetic studies and mouse models that supports SHANK3 haploinsufficiency as a major contributor of the neurobehavioral manifestations of Phelan-McDermid syndrome. Finally, we discuss how all these discoveries are uncovering the pathophysiology of Phelan-McDermid syndrome and are being translated into clinical trials for novel therapeutics ameliorating the core symptoms of the disorder.

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3. Gipson TT, Poretti A, Thomas EA, Jenkins KT, Desai S, Johnston MV. Autism Phenotypes in Tuberous Sclerosis Complex : Diagnostic and Treatment Considerations. Journal of child neurology. 2015 December 1, 2015 ;30(14):1871-6.

Tuberous sclerosis complex is a multisystem, chronic genetic condition characterized by systemic growth of benign tumors and often accompanied by epilepsy, autism spectrum disorders, and intellectual disability. Nonetheless, the neurodevelopmental phenotype of these patients is not often detailed. The authors describe 3 individuals with tuberous sclerosis complex who share common characteristics that can help to identify a distinct profile of autism spectrum disorder. These findings include typical cognitive development, expressive and pragmatic language deficits, and anxiety. The authors also describe features specific to tuberous sclerosis complex that require consideration before diagnosing an autism spectrum disorder. Identifying distinct profiles of autism spectrum disorder in tuberous sclerosis complex can help optimize treatment across the life span.

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4. Sharer E, Crocetti D, Muschelli J, Barber AD, Nebel MB, Caffo BS, Pekar JJ, Mostofsky SH. Neural Correlates of Visuomotor Learning in Autism. Journal of child neurology. 2015 December 1, 2015 ;30(14):1877-86.

Motor impairments are prevalent in children with autism spectrum disorder. The Serial Reaction Time Task, a well-established visuomotor sequence learning probe, has produced inconsistent behavioral findings in individuals with autism. Moreover, it remains unclear how underlying neural processes for visuomotor learning in children with autism compare to processes for typically developing children. Neural activity differences were assessed using functional magnetic resonance imaging during a modified version of the Serial Reaction Time Task in children with and without autism. Though there was no group difference in visuomotor sequence learning, underlying patterns of neural activation significantly differed when comparing sequence (ie, learning) to random (ie, nonlearning) blocks. Children with autism demonstrated decreased activity in brain regions implicated in visuomotor sequence learning : superior temporal sulcus and posterior cingulate cortex. The findings implicate differences in brain mechanisms that support initial sequence learning in autism and can help explain behavioral observations of autism-associated impairments in skill development (motor, social, communicative) reliant on visuomotor integration.

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5. Germain B, Eppinger MA, Mostofsky SH, DiCicco-Bloom E, Maria BL. Recent Advances in Understanding and Managing Autism Spectrum Disorders. Journal of child neurology. 2015 December 1, 2015 ;30(14):1887-920.

Autism spectrum disorder in children is a group of neurodevelopmental disorders characterized by difficulties with social communication and behavior. Growing scientific evidence in addition to clinical practice has led the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to categorize several disorders into the broader category of autism spectrum disorder. As more is learned about how autism spectrum disorder manifests, progress has been made toward better clinical management including earlier diagnosis, care, and when specific interventions are required. The 2014 Neurobiology of Disease in Children symposium, held in conjunction with the 43rd annual meeting of the Child Neurology Society, aimed to (1) describe the clinical concerns involving diagnosis and treatment, (2) review the current status of understanding in the pathogenesis of autism spectrum disorder, (3) discuss clinical management and therapies for autism spectrum disorder, and (4) define future directions of research. The article summarizes the presentations and includes an edited transcript of question-and-answer sessions.

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6. Sacrey L-AR, Bennett JA, Zwaigenbaum L. Early Infant Development and Intervention for Autism Spectrum Disorder. Journal of child neurology. 2015 December 1, 2015 ;30(14):1921-9.

Objective : The objective is to overview recent findings on early detection/diagnosis of autism spectrum disorders, as well as clinical trials of early interventions for toddlers at risk for/diagnosed with autism spectrum disorder.Findings : Prospective studies of infants at high risk of autism spectrum disorder have yielded significant advances in understanding early development in autism spectrum disorder. Findings from prospective studies indicate that abnormalities in social communication and repetitive behaviors emerge during the second year, whereas additional “prodromal features” (motor and sensory abnormalities) emerge in the first year. Subsequently, exciting progress has been made in establishing the efficacy of autism spectrum disorder–specific interventions for toddlers as young as 15 months. Finally, efforts occur to characterize autism spectrum disorder–specific characteristics in genetic syndromes with concurrent autism spectrum disorder symptomatology.Conclusion : Substantial progress in characterizing early developmental trajectories as well as the identification of specific behavioral markers has aided early detection. Work remains to ensure that research findings are translated into clinical practice for uptake in the health care system.

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7. Stamova B, Ander BP, Barger N, Sharp FR, Schumann CM. Specific Regional and Age-Related Small Noncoding RNA Expression Patterns Within Superior Temporal Gyrus of Typical Human Brains Are Less Distinct in Autism Brains. Journal of child neurology. 2015 December 1, 2015 ;30(14):1930-46.

Small noncoding RNAs play a critical role in regulating messenger RNA throughout brain development and when altered could have profound effects leading to disorders such as autism spectrum disorders (ASD). We assessed small noncoding RNAs, including microRNA and small nucleolar RNA, in superior temporal sulcus association cortex and primary auditory cortex in typical and ASD brains from early childhood to adulthood. Typical small noncoding RNA expression profiles were less distinct in ASD, both between regions and changes with age. Typical micro-RNA coexpression associations were absent in ASD brains. miR-132, miR-103, and miR-320 micro-RNAs were dysregulated in ASD and have previously been associated with autism spectrum disorders. These diminished region- and age-related micro-RNA expression profiles are in line with previously reported findings of attenuated messenger RNA and long noncoding RNA in ASD brain. This study demonstrates alterations in superior temporal sulcus in ASD, a region implicated in social impairment, and is the first to demonstrate molecular alterations in the primary auditory cortex.

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8. Kusenda M, Vacic V, Malhotra D, Rodgers L, Pavon K, Meth J, Kumar RA, Christian SL, Peeters H, Cho SS, Addington A, Rapoport JL, Sebat J. The Influence of Microdeletions and Microduplications of 16p11.2 on Global Transcription Profiles. Journal of child neurology. 2015 December 1, 2015 ;30(14):1947-53.

Copy number variants (CNVs) of a 600 kb region on 16p11.2 are associated with neurodevelopmental disorders and changes in brain volume. The authors hypothesize that abnormal brain development associated with this CNV can be attributed to changes in transcriptional regulation. The authors determined the effects of 16p11.2 dosage on gene expression by transcription profiling of lymphoblast cell lines derived from 6 microdeletion carriers, 15 microduplication carriers and 15 controls. Gene dosage had a significant influence on the transcript abundance of a majority (20/34) of genes within the CNV region. In addition, a limited number of genes were dysregulated in trans. Genes most strongly correlated with patient head circumference included SULT1A, KCTD13, and TMEM242. Given the modest effect of 16p11.2 copy number on global transcriptional regulation in lymphocytes, larger studies utilizing neuronal cell types may be needed in order to elucidate the signaling pathways that influence brain development in this genetic disorder.

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9. Sundberg M, Sahin M. Cerebellar Development and Autism Spectrum Disorder in Tuberous Sclerosis Complex. Journal of child neurology. 2015 December 1, 2015 ;30(14):1954-62.

Approximately 50% of patients with the genetic disease tuberous sclerosis complex present with autism spectrum disorder. Although a number of studies have investigated the link between autism and tuberous sclerosis complex, the etiology of autism spectrum disorder in these patients remains unclear. Abnormal cerebellar function during critical phases of development could disrupt functional processes in the brain, leading to development of autistic features. Accordingly, the authors review the potential role of cerebellar dysfunction in the pathogenesis of autism spectrum disorder in tuberous sclerosis complex. The authors also introduce conditional knockout mouse models of Tsc1 and Tsc2 that link cerebellar circuitry to the development of autistic-like features. Taken together, these preclinical and clinical investigations indicate the cerebellum has a profound regulatory role during development of social communication and repetitive behaviors.

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10. Jeste SS, Tuchman R. Autism Spectrum Disorder and Epilepsy : Two Sides of the Same Coin ?. Journal of child neurology. 2015 December 1, 2015 ;30(14):1963-71.

Autism spectrum disorders and epilepsy commonly co-occur. In this review, we consider some unresolved questions regarding the temporal relationship, causal mechanisms, and clinical stratification of this comorbidity, highlighting throughout the interplay between autism spectrum disorder, epilepsy, and intellectual disability. We present data on the clinical characterization of children with autism spectrum disorder and epilepsy, discussing distinctive phenotypes in children with this comorbidity. Although some distinctive clinical features emerge, this comorbidity also informs convergent pathways in genetic variants that cause synaptic dysfunction. We then move beyond diagnostic categorization and consider the extent to which electrophysiology as a quantitative biomarker may help guide efforts in clinical stratification and outcome prediction. Epilepsy, and atypical electrophysiological patterns, in autism spectrum disorder may inform the definition of biologically meaningful subgroups within the spectrum that, in turn, can shed light on potential targets for intervention.

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