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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

FOXP2, the first gene to have been implicated in a developmental communication disorder, offers a unique entry point into neuromolecular mechanisms influencing human speech and language acquisition. In multiple members of the well-studied KE family, a heterozygous missense mutation in FOXP2 causes problems in sequencing muscle movements required for articulating speech (developmental verbal dyspraxia), accompanied by wider deficits in linguistic and grammatical processing. Chromosomal rearrangements involving this locus have also been identified. Analyses of FOXP2 coding sequence in typical forms of specific language impairment (SLI), autism, and dyslexia have not uncovered any etiological variants. However, no previous study has performed mutation screening of children with a primary diagnosis of verbal dyspraxia, the most overt feature of the disorder in affected members of the KE family. Here, we report investigations of the entire coding region of FOXP2, including alternatively spliced exons, in 49 probands affected with verbal dyspraxia. We detected variants that alter FOXP2 protein sequence in three probands. One such variant is a heterozygous nonsense mutation that yields a dramatically truncated protein product and cosegregates with speech and language difficulties in the proband, his affected sibling, and their mother. Our discovery of the first nonsense mutation in FOXP2 now opens the door for detailed investigations of neurodevelopment in people carrying different etiological variants of the gene. This endeavor will be crucial for gaining insight into the role of FOXP2 in human cognition.
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PMID:Identification of FOXP2 truncation as a novel cause of developmental speech and language deficits. 1587 81

When a child's language development does not follow the normal developmental course for no known reasons specific language impairment (SLI) is diagnosed. In contrast, pragmatic language impairment (PLI) refers to children who experience significant difficulties with the use of language. Clinical accounts of PLI have suggested that unlike children with more typical SLI, children with PLI have adequate syntax and phonology and are often verbally fluent. However, they may exhibit a range of linguistic and communicative deficits such as comprehension deficits for connected speech, conversational inadequacies, poor turn-taking, atypical word choices, literal interpretation of figurative language, and poor topic maintenance. There also may be fundamental deficits in social cognition, such as appreciating the thoughts and feelings of others. PLI may be found in SLI children, children with learning disabilities, autism and traumatic brain injuries. Here we review aspects of pragmatic communication skills, the development of emotion recognition, and diagnostic and therapeutic procedures. Otolaryngologists have to be aware of PLI in case children with communication problems are referred to them. This may enable a timely diagnosis and early intervention.
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PMID:[Pragmatic language impairment in children]. 1590 45

Neurobiology of speech and language has previously been studied in the KE family, in which half of the members have severe impairment in both speech and language. The gene responsible for the phenotype was mapped to chromosome 7q31 and identified as the FOXP2 gene, coding for a transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain. Because of linkage studies implicating 7q31 in autism, where language impairment is a component of the disorder, and in specific language impairment, FOXP2 has also been considered as a potential susceptibility locus for the language deficits in autism and/or specific language impairment. In this study, we characterized mice with a disruption in the murine Foxp2 gene. Disruption of both copies of the Foxp2 gene caused severe motor impairment, premature death, and an absence of ultrasonic vocalizations that are elicited when pups are removed from their mothers. Disruption of a single copy of the gene led to modest developmental delay but a significant alteration in ultrasonic vocalization in response to such separation. Learning and memory appear normal in the heterozygous animals. Cerebellar abnormalities were observed in mice with disruptions in Foxp2, with Purkinje cells particularly affected. Our findings support a role for Foxp2 in cerebellar development and in a developmental process that subsumes social communication functions in diverse organisms.
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PMID:Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene. 1598 71

Department of Psychology, Birkbeck College, University of London, UK High-functioning children with autism show a severe deficit in the development of pragmatics whereas their knowledge of syntax and morphology is relatively intact. In this study we investigated further their selective communication impairment by comparing them with children with specific language impairment (SLI) and normally developing children. We used a pragmatic task that involved the detection of utterances that violate conversational maxims (avoid redundancy, be informative, truthful, relevant, and polite). Most children with autism performed at chance on this task, whereas all children with SLI and all normal controls performed above chance. In addition, the success of children with autism on the pragmatics task was related to their ability to attribute false beliefs. These results are consistent with the idea that communication deficits in autism result from a selective impairment in representing propositional attitudes. Their implications for domain-specific views of cognitive development are discussed.
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PMID:Are children with autism deaf to gricean maxims? 1657 74

Three studies concerning catatonia-like clinical pictures in people with autism spectrum disorders (ASDs) referred to clinics are described. The first investigated the frequencies, in children and adults with autistic disorders, of 28 specific disorders of movement, speech, and behavior similar to those occurring in chronic catatonia spectrum conditions. The second compared the frequency of these items among groups of children with, ASDs, learning disabilities, specific language impairment, and a group with typical development, respectively. The third study examined the pattern of catatonia-like deterioration occurring in a minority of adolescents and adults with ASDs. The studies demonstrated the high frequency of catatonia-like features in people with autistic disorders. There was some tendency for improvement with increasing age, especially for those with IQ 70 or over. The items were also found in children with learning disabilities and specific language disorders but significantly less often. They occurred least often in the children with typical development. Severe catatonia-like deterioration occurred in 17% of those with autistic disorders, who were aged 15 years or over when assessed at a diagnostic center. A history of passivity in social interaction and impairment of expressive language were associated with the deterioration. No clear relationship was found between a history of catatonia-like features, singly or combined, and catatonia-like deterioration. The findings pose questions for future research.
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PMID:A systematic examination of catatonia-like clinical pictures in autism spectrum disorders. 1669 89

Autism involves primary impairments in both language and communication, yet in recent years the main focus of research has been on the communicative deficits that define the population. The study reported in this paper investigated language functioning in a group of 89 children diagnosed with autism using the ADI-R, and meeting DSM-IV criteria. The children, who were between 4- and 14- years-old were administered a battery of standardized language tests tapping phonological, lexical, and higher-order language abilities. The main findings were that among the children with autism there was significant heterogeneity in their language skills, although across all the children, articulation skills were spared. Different subgroups of children with autism were identified on the basis on their performance on the language measures. Some children with autism have normal language skills; for other children, their language skills are significantly below age expectations. The profile of performance across the standardized measures for the language-impaired children with autism was similar to the profile that defines the disorder specific language impairment (or SLI). The implications of this language impaired subgroup in autism for understanding the genetics and definition of both autism and SLI are discussed.
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PMID:An Investigation of Language Impairment in Autism: Implications for Genetic Subgroups. 1670 15

Children with autism have delays in the development of theory of mind. However, the sub-group of children with autism who have little or no language have gone untested since false belief tests (FB) typically involve language. FB understanding has been reported to be intact in children with specific language impairment (SLI). This raises the possibility that a non-verbal FB test would distinguish children with autism vs. children with SLI. The present study tested two predictions: (1) FB understanding is to some extent independent of language ability; and (2) Children with autism with low language levels show specific impairment in theory of mind. Results confirmed both predictions. Results are discussed in terms of the role of language in the development of mindreading.
J Autism Dev Disord 2007 Apr
PMID:Do children with autism have a theory of mind? A non-verbal test of autism vs. specific language impairment. 1697 96

While the primary language deficit in autism has been thought to be pragmatic, and in specific language impairment (SLI) structural, recent research suggests phenomenological and possibly genetic overlap between the two syndromes. To compare communicative competence in parents of children with autism, SLI, and down syndrome (DS), we used a modified pragmatic rating scale (PRS-M). Videotapes of conversational interviews with 47 autism, 47 SLI, and 21 DS parents were scored blind to group membership. Autism and SLI parents had significantly lower communication abilities than DS parents. Fifteen percent of the autism and SLI parents showed severe deficits. Our results suggest that impaired communication is part of the broader autism phenotype and a broader SLI phenotype, especially among male family members.
J Autism Dev Disord 2007 Aug
PMID:Communicative competence in parents of children with autism and parents of children with specific language impairment. 1718 Apr 60

Genetic factors are important contributors to language and learning disorders, and discovery of the underlying genes can help delineate the basic neurological pathways that are involved. This information, in turn, can help define disorders and their perceptual and processing deficits. Initial molecular genetic studies of dyslexia, for example, appear to converge on defects in neuronal and axonal migration. Further study of individuals with abnormalities of these genes may lead to the recognition of characteristic cognitive deficits attributable to the neurological dysfunction. Such abnormalities may affect other disorders as well, and studies of co-morbidity of dyslexia with attention deficit disorder and speech sound disorder are helping to define the scope of these genes and show the etiological and cognitive commonalities between these conditions. The genetic contributions to specific language impairment (SLI) are not as well defined at this time, but similar molecular approaches are being applied to identify genes that influence SLI and comorbid disorders. While there is co-morbidity of SLI with dyslexia, it appears that most of the common genetic effects may be with the language characteristics of autism spectrum disorders rather than with dyslexia and related disorders. Identification of these genes and their neurological and cognitive effects should lay out a functional network of interacting genes and pathways that subserve language development. Understanding these processes can form the basis for refined procedures for diagnosis and treatment.
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PMID:Genes, language development, and language disorders. 1732 14

We report on a young male with moderate mental retardation, dysmorphic features, and language delay who is deleted for 7q31.1-7q31.31. His full karyotype is 46,XY,der(7)del(7)(q31.1q31.31)ins(10;7)(q24.3;q31.1q31.31)mat. This child had language impairment, including developmental verbal dyspraxia, but did not meet criteria for autism according to standardized ADOS testing. Our patient's deletion, which is the smallest reported deletion including FOXP2, adds to the body of evidence that supports the role of FOXP2 in speech and language impairment, but not in autism. A reported association between autism and deletions of WNT2, a gene also deleted in our patient, is likewise not supported by our case. Previously, fine mapping with microsatellites markers within in a large three-generation family, in which half the members had severe specific language impairment, aided the localization of the SPCH1 locus to 7q31 within markers D7S2459 (107.1 Mb) and D7S643 (120.5 Mb). Additionally, chromosome rearrangement of 7q31 and mutational analyses have supported the growing evidence that FOXP2, a gene within the SPCH1 region, is involved with speech and language development. It is unclear however whether the AUTS1 (autistic spectrum 1) locus, highly linked to 7q31, overlaps with the SPCH1 and FOXP2.
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PMID:Deletion of 7q31.1 supports involvement of FOXP2 in language impairment: clinical report and review. 1733 Aug 59


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