MRI Findings in 77 Children with Non-Syndromic Autistic Disorder

International audienceBACKGROUND: The clinical relevance of MR scanning in children with autism is still an open question and must be considered in light of the evolution of this technology. MRI was judged to be of insufficient value to be included in the standard clinical evaluation of autism according to the guidelines of the American Academy of Neurology and Child Neurology Society in 2000. However, this statement was based on results obtained from small samples of patients and, more importantly, included mostly insufficient MRI sequences. Our main objective was to evaluate the prevalence of brain abnormalities in a large group of children with a non-syndromic autistic disorder (AD) using T1, T2 and FLAIR MRI sequences. METHODOLOGY: MRI inspection of 77 children and adolescents with non-syndromic AD (mean age 7.4+/-3.6) was performed. All met the DSM-IV and ADI -R criteria for autism. Based on recommended clinical and biological screenings, we excluded patients with infectious, metabolic or genetic diseases, seizures or any other neurological symptoms. Identical MRI inspections of 77 children (mean age 7.0+/-4.2) without AD, developmental or neurological disorders were also performed. All MRIs were acquired with a 1.5-T Signa GE (3-D T1-FSPGR, T2, FLAIR coronal and axial sequences). Two neuroradiologists independently inspected cortical and sub-cortical regions. MRIs were reported to be normal, abnormal or uninterpretable. PRINCIPAL FINDINGS: MRIs were judged as uninterpretable in 10% (8/77) of the cases. In 48% of the children (33/69 patients), abnormalities were reported. Three predominant abnormalities were observed, including white matter signal abnormalities (19/69), major dilated Virchow-Robin spaces (12/69) and temporal lobe abnormalities (20/69). In all, 52% of the MRIs were interpreted as normal (36/69 patients). CONCLUSIONS: An unexpectedly high rate of MRI abnormalities was found in the first large series of clinical MRI investigations in non-syndromic autism. These results could contribute to further etiopathogenetic research into autism

Early-onset catatonia associated with SHANK3 mutations: looking at the autism spectrum through the prism of psychomotor phenomena

BackgroundIndividuals with Phelan-McDermid syndrome (PMS) present with a wide range of diagnoses: autism spectrum disorder, intellectual disability, or schizophrenia. Differences in the genetic background could explain these different neurodevelopmental trajectories. However, a more parsimonious hypothesis is to consider that they may be the same phenotypic entity. Catatonic disturbances occasionally reported from adolescence onwards in PMS prompts exploration of the hypothesis that this clinical entity may be an early-onset form of catatonia. The largest cohort of children with childhood catatonia was studied by the Wernicke-Kleist-Leonhard school (WKL school), which regards catatonia as a collection of qualitative abnormalities of psychomotricity that predominantly affecting involuntary motricity (reactive and expressive). The aim of this study was to investigate the presence of psychomotor signs in three young adults carrying a mutation or intragenic deletion of the SHANK3 gene through the prism of the WKL school conception of catatonia.MethodsThis study was designed as an exploratory case study. Current and childhood psychomotor phenomena were investigated through semi-structured interviews with the parents, direct interaction with the participants, and the study of documents reporting observations of the participants at school or by other healthcare professionals.ResultsThe findings show catatonic manifestations from childhood that evolved into a chronic form, with possible phases of sub-acute exacerbations starting from adolescence.ConclusionThe presence of catatonic symptoms from childhood associated with autistic traits leads us to consider that this singular entity fundamentally related to SHANK3 mutations could be a form of early-onset catatonia. Further case studies are needed to confirm our observations

Case report: an unexpected link between partial deletion of the SHANK3 gene and Heller’s dementia infantilis, a rare subtype of autism spectrum disorder

International audienceAbstractBackgroundDeletions and mutations involving the SHANK3 gene lead to a nonspecific clinical presentation with moderate to profound intellectual disability, severely delayed or absent speech, and autism spectrum disorders (ASD).Better knowledge of the clinical spectrum of SHANK3 haploinsufficiency is useful to facilitate clinical care monitoring and to guide molecular diagnosis, essential for genetic counselling.Case presentationHere, we report a detailed clinical description of a 10-year-old girl carrying a pathogenic interstitial 22q13.3 deletion encompassing only the first 17 exons of SHANK3.The clinical features displayed by the girl strongly suggested the diagnosis of dementia infantilis, described by Heller in 1908, also known as childhood disintegrative disorder.ConclusionOur present case confirms several observations according to which regression may be part of the clinical phenotype of SHANK3 haploinsufficiency. Therefore, we think it is crucial to look for mutations in the gene SHANK3 in patients diagnosed for childhood disintegrative disorder or any developmental disorder with a regressive pattern involving social and communicative skills as well as cognitive and instinctual functions, with onset around 3 years

Regard pédopsychiatrique sur le diagnostic de dysphasie

Dysphasia is a severe and persistent disorder of oral language development. Usually, the effect on language development is said to be “specific,” that is, something not traceable to an identifiable clinical cause. Because of the complexity of diagnosing dysphasia, we felt it necessary to first make a synthetic compendium of the state of research in the domain based on a review of the literature. In the second part of the article, we will formalize some of our questions concerning the diagnosis and the notion of specificity, born of the confrontation between our clinical experience and the salient points of current research. On the basis of this clinical practice and with the support of the aforementioned research, the authors advocate for the necessity of a psychiatric evaluation of all children in whom dysphasia is suspected or diagnosed.La dysphasie est un trouble sévère et persistant du développement du langage oral. Classiquement, l’atteinte du développement du langage est dite « spécifique », c’est à dire ne relevant pas d’une cause cliniquement identifiable. Devant la complexité du diagnostic de dysphasie, il nous a paru nécessaire de dresser un état des lieux synthétique de l’état des recherches dans le domaine à partir d’une revue de la littérature. Dans une seconde partie, nous formalisons certains de nos questionnements autour de ce diagnostic et de la notion de spécificité, nés de la confrontation entre notre expérience clinique et les points saillants des recherches actuelles. Au vu de leur pratique clinique, et étayés de leurs recherches, les auteurs plaident pour l’impérative nécessité d’une évaluation pédopsychiatrique chez tous les enfants chez lesquels une dysphasie est suspectée ou diagnostiquée

Automatic Intonation Recognition for the Prosodic Assessment of Language-Impaired Children

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Clinical, cellular, and neuropathological consequences of AP1S2 mutations: further delineation of a recognizable X-linked mental retardation syndrome

International audienceCommunicated by Andreas Gal Mutations in the AP1S2 gene, encoding the r1B subunit of the clathrin-associated adaptor protein complex (AP)-1, have been recently identified in five X-linked mental retardation (XLMR) families, including the original family with Fried syndrome. Studying four patients in two unrelated families in which AP1S2 nonsense and splice-site mutations segregated, we found that affected individuals presented, in addition to previously described features, with elevated protein levels in cerebrospinal fluid (CSF). Moreover, computed tomography scans demonstrated that the basal ganglia calcifications associated with AP1S2 mutations appeared during childhood and might be progressive. Based on these observations, we propose that AP1S2 mutations are responsible for a clinically recognizable XLMR and autism syndrome associating hypotonia, delayed walking, speech delay, aggressive behavior, brain calcifications, and elevated CSF protein levels. Using the AP-2 complex, in which the r subunit is encoded by one single gene, as a model system, we demonstrated that r subunits are essential for the stability of human AP complexes. By contrast, no major alteration of the stability, subcellular localization, and function of the AP-1 complex was observed in fibroblasts derived from a patient carrying an AP1S2 mutation. Similarly, neither macro-nor microscopic defects were observed in the brain of an affected fetus. Altogether, these data suggest that the absence of an AP-1 defect in peripheral tissues is due to functional redundancy among AP-1 r subunits (r1A, r1B, and r1C) and that the phenotype observed in our patients results from a subtle and brain-specific defect of the AP-1-dependent intracellular protein traffic. Hum Mutat 29(7), 966-974, 2008. r r 2008 Wiley-Liss, Inc

Tracking Social Motivation Systems Deficits: The Affective Neuroscience View of Autism

International audienceAbnormal functioning of primary brain systems that express and modulate basic emotional drives are increasingly considered to underlie mental disorders including autism spectrum disorders. We hypothesized that ASD are characterized by disruptions in the primary systems involved in the motivation for social bonding. Twenty adults with ASD were compared to 20 neurotypical participants on the basis of self-reports and clinical assessments, including the Social Anhedonia Scale (SAS) and the Affective Neuroscience Personality Scales (ANPS). ASD diagnosis was related to SAS, as well as to positive (PLAYFULNESS) and negative (FEAR) ANPS-traits. In the overall sample, levels of autistic traits (AQ) were related to SAS and PLAYFULNESS. We argue that PLAYFULNESS could be at the root of social bonding impairments in ASD

Differential language markers of pathology in Autism, Pervasive Developmental Disorder Not Otherwise Specified and Specific Language Impairment

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Infant’s engagement and emotion as predictors of autism or intellectual disability in West syndrome

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