Dataset Information

Characterisation of CASPR2 deficiency disorder--a syndrome involving autism, epilepsy and language impairment.

ABSTRACT:

Background

Heterozygous mutations in CNTNAP2 have been identified in patients with a range of complex phenotypes including intellectual disability, autism and schizophrenia. However heterozygous CNTNAP2 mutations are also found in the normal population. Conversely, homozygous mutations are rare in patient populations and have not been found in any unaffected individuals.

Case presentation

We describe a consanguineous family carrying a deletion in CNTNAP2 predicted to abolish function of its protein product, CASPR2. Homozygous family members display epilepsy, facial dysmorphisms, severe intellectual disability and impaired language. We compared these patients with previously reported individuals carrying homozygous mutations in CNTNAP2 and identified a highly recognisable phenotype.

Conclusions

We propose that CASPR2 loss produces a syndrome involving early-onset refractory epilepsy, intellectual disability, language impairment and autistic features that can be recognized as CASPR2 deficiency disorder. Further screening for homozygous patients meeting these criteria, together with detailed phenotypic and molecular investigations will be crucial for understanding the contribution of CNTNAP2 to normal and disrupted development.

SUBMITTER: Rodenas-Cuadrado P

PROVIDER: S-EPMC4739328 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Publications

Characterisation of CASPR2 deficiency disorder--a syndrome involving autism, epilepsy and language impairment.

Rodenas-Cuadrado Pedro P Pietrafusa Nicola N Francavilla Teresa T La Neve Angela A Striano Pasquale P Vernes Sonja C SC

BMC medical genetics 20160203

<h4>Background</h4>Heterozygous mutations in CNTNAP2 have been identified in patients with a range of complex phenotypes including intellectual disability, autism and schizophrenia. However heterozygous CNTNAP2 mutations are also found in the normal population. Conversely, homozygous mutations are rare in patient populations and have not been found in any unaffected individuals.<h4>Case presentation</h4>We describe a consanguineous family carrying a deletion in CNTNAP2 predicted to abolish funct ...[more]

PMID: 26843181

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Project description:Language is one of the cognitive domains often impaired across many neurodevelopmental disorders. While for some disorders the linguistic deficit is the primary impairment (e.g., specific language impairment, SLI), for others it may accompany broader behavioral problems (e.g., autism). The precise nature of this phenotypic overlap has been the subject of debate. Moreover, several studies have found genetic overlaps across neurodevelopmental disorders. This raises the question of whether these genetic overlaps may correlate with phenotypic overlaps and, if so, in what manner. Here, we apply a genome-wide approach to the study of the linguistic deficit in SLI, autism spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). Using a discovery genome-wide association study of SLI, we generate polygenic risk scores (PRS) in an independent sample which includes children with language impairment, SLI, ASD or ADHD and age-matched controls and perform regression analyses across groups. The SLI-trained PRS significantly predicted risk in the SLI case-control group (adjusted R2 = 6.24%; P = 0.024) but not in the ASD or ADHD case-control groups (adjusted R2 = 0.0004%, 0.01%; P = 0.984, 0.889, respectively) nor for height, used as a negative control (R2 = 0.2%; P = 0.452). Additionally, there was a significant difference in the normalized PRS between children with SLI and children with ASD (common language effect size = 0.66; P = 0.044). Our study suggests no additive common-variant genetic overlap between SLI and ASD and ADHD. This is discussed in the context of phenotypic studies of SLI and related disorders. Autism Res 2020, 13: 369-381. © 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: Language deficits are characteristic of specific language impairment (SLI), but may also be found in other neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Many studies examined the overlaps and differences across the language deficits in these disorders, but few studies have examined the genetic aspect thereof. In this study, we use a genome-wide approach to evaluate whether common genetic variants increasing risk of SLI may also be associated with ASD and ADHD in the same manner. Our results suggest that this is not the case, and we discuss this finding in the context of theories concerning the etiologies of these disorders.

Project description:BackgroundWord learning is an important component of language development that influences child outcomes across multiple domains. Despite the importance of word knowledge, word-learning mechanisms are poorly understood in children with specific language impairment (SLI) and children with autism spectrum disorder (ASD). This study examined underlying mechanisms of word learning, specifically, statistical learning and fast-mapping, in school-aged children with typical and atypical development.MethodsStatistical learning was assessed through a word segmentation task and fast-mapping was examined in an object-label association task. We also examined children's ability to map meaning onto newly segmented words in a third task that combined exposure to an artificial language and a fast-mapping task.ResultsChildren with SLI had poorer performance on the word segmentation and fast-mapping tasks relative to the typically developing and ASD groups, who did not differ from one another. However, when children with SLI were exposed to an artificial language with phonemes used in the subsequent fast-mapping task, they successfully learned more words than in the isolated fast-mapping task. There was some evidence that word segmentation abilities are associated with word learning in school-aged children with typical development and ASD, but not SLI. Follow-up analyses also examined performance in children with ASD who did and did not have a language impairment. Children with ASD with language impairment evidenced intact statistical learning abilities, but subtle weaknesses in fast-mapping abilities.ConclusionsAs the Procedural Deficit Hypothesis (PDH) predicts, children with SLI have impairments in statistical learning. However, children with SLI also have impairments in fast-mapping. Nonetheless, they are able to take advantage of additional phonological exposure to boost subsequent word-learning performance. In contrast to the PDH, children with ASD appear to have intact statistical learning, regardless of language status; however, fast-mapping abilities differ according to broader language skills.

Dataset Information

Characterisation of CASPR2 deficiency disorder--a syndrome involving autism, epilepsy and language impairment.

Background

Case presentation

Conclusions

Publications

Characterisation of CASPR2 deficiency disorder--a syndrome involving autism, epilepsy and language impairment.

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