Early Screening of the Autism Spectrum Disorders: Validity Properties and Cross-Cultural Generalizability of the First Year Inventory in Italy.

This study examined the cross-cultural generalisability of the First Year Inventory (FYI) on an Italian sample, testing its construct validity, consistency, and structural validity. Six hundred ninety-eight parents of children aged 11-13 months completed the questionnaire. Similarities between analyses of Italian and American/Israeli samples were found, as were demonstrations of the instrument's construct validity and internal consistency with both groups. The original factorial structure was not demonstrated; thus, a new factorial structure was tested, and a short version of the FYI was demonstrated via confirmatory factor analysis. The findings supported the generalisability of the Italian version of the FYI and its validity. The FYI may aid in medical decision-making on further steps for referral of the child to an early diagnostic assessment.

Association Analysis of Noncoding Variants in Neuroligins 3 and 4X Genes with Autism Spectrum Disorder in an Italian Cohort.

Since involved in synaptic transmission and located on X-chromosome, neuroligins 3 and 4X have been studied as good positional and functional candidate genes for autism spectrum disorder pathogenesis, although contradictory results have been reported. Here, we performed a case-control study to assess the association between noncoding genetic variants in NLGN3 and NLGN4X genes and autism, in an Italian cohort of 202 autistic children analyzed by high-resolution melting. The results were first compared with data from 379 European healthy controls (1000 Genomes Project) and then with those from 1061 Italian controls genotyped by Illumina single nucleotide polymorphism (SNP) array 1M-duo. Statistical evaluations were performed using Plink v1.07, with the Omnibus multiple loci approach. According to both the European and the Italian control groups, a 6-marker haplotype on NLGN4X (rs6638575(G), rs3810688(T), rs3810687(G), rs3810686(C), rs5916269(G), rs1882260(T)) was associated with autism (odd ratio = 3.58, p-value = 2.58 × 10-6 for the European controls; odds ratio = 2.42, p-value = 6.33 × 10-3 for the Italian controls). Furthermore, several haplotype blocks at 5-, 4-, 3-, and 2-, including the first 5, 4, 3, and 2 SNPs, respectively, showed a similar association with autism. We provide evidence that noncoding polymorphisms on NLGN4X may be associated to autism, suggesting the key role of NLGN4X in autism pathophysiology and in its male prevalence.

"Put Myself Into Your Place": Embodied Simulation and Perspective Taking in Autism Spectrum Disorders.

Embodied cognition theories hold that cognitive processes are grounded in bodily states. Embodied processes in autism spectrum disorders (ASD) have classically been investigated in studies on imitation. Several observations suggested that unlike typical individuals who are able of copying the model's actions from the model's position, individuals with ASD tend to reenact the model's actions from their own egocentric perspective. Here, we performed two behavioral experiments to directly test the ability of ASD individuals to adopt another person's point of view. In Experiment 1, participants had to explicitly judge the left/right location of a target object in a scene from their own or the actor's point of view (visual perspective taking task). In Experiment 2, participants had to perform left/right judgments on front-facing or back-facing human body images (own body transformation task). Both tasks can be solved by mentally simulating one's own body motion to imagine oneself transforming into the position of another person (embodied simulation strategy), or by resorting to visual/spatial processes, such as mental object rotation (nonembodied strategy). Results of both experiments showed that individual with ASD solved the tasks mainly relying on a nonembodied strategy, whereas typical controls adopted an embodied strategy. Moreover, in the visual perspective taking task ASD participants had more difficulties than controls in inhibiting other-perspective when directed to keep one's own point of view. These findings suggested that, in social cognitive tasks, individuals with ASD do not resort to embodied simulation and have difficulties in cognitive control over self- and other-perspective.

Genotype-phenotype relationship in a child with 2.3 Mb de novo interstitial 12p13.33-p13.32 deletion.

Microdeletion 12p13.33, though very rare, is an emerging condition associated with variable phenotype including a specific speech delay sound disorder, labelled childhood apraxia of speech (CAS), intellectual disability (ID) and neurobehavioral problems. Here we report a de novo 2.3 Mb interstitial 12p13.33-p13.32 deletion in a 5 year-old child with mild ID, speech delay, microcephaly, muscular hypotonia, and joint laxity. In contrast to previously reported patients with 12p13.33 monosomy, our patient's interstitial deletion spans the 12p13.33-12p13.32 region with the distal breakpoint within intron 12 of CACNA1C. Phenotype-genotype comparison between our case, previously reported patients, and subjects with 12p13.33 deletions led us to propose that haploinsufficiency of CACNA1C may influence the variability of the patients' phenotype, since the gene resulted disrupted or entirely deleted in the majority of reported patients. In addition, phenotypic features such as microcephaly, muscular hypotonia, and joint laxity are mainly present in patients with monosomy of 12p13.33 extending to the 12p13.32 portion. A common region of ~300 kb, harbouring EFCAB4B and PARP11, is deleted in patients with microcephaly while a second region of ~700 kb, including TSPAN9 and PMTR8, could be associated with muscle hypotonia and joint laxity. These data reinforce the hypothesis that multiple haploinsufficient genes and age-dependent observation may concur to generate the variable phenotype associated with 12p13.33 deletion.

Long-term effects of PECS on social-communicative skills of children with autism spectrum disorders: a follow-up study.

BACKGROUND: The Picture Exchange Communication System (PECS) is a popular augmentative communication system frequently used with 'nonverbal' children with autism. Several studies suggested that PECS could represent an effective tool for promoting improvement of several social-communicative skills. Only sparse evidence is instead available on the long-term effectiveness of this treatment system. AIMS: To test the long-term effects of PECS, for which a follow-up study was conducted by assessing social-communicative skills in nonverbal preschool children with autism after 12 months from treatment completion. METHODS & PROCEDURES: Two groups of children (N = 14) were assessed; one group had completed the PECS training and the other conventional language therapy (CLT). At follow-up all children received the same pre- and post-treatment assessment. Outcome measures were the following: Communication and Social domains of Autism Diagnostic Observation Schedule (ADOS); Language and Personal-Social subscales of the Griffiths' Mental Developmental Scales (GMDS); Communication and Social Abilities domains of the Vineland Adaptive Behavior Scales (VABS); and several social-communicative variables coded in an unstructured setting. OUTCOMES & RESULTS: The PECS group showed significant improvements compared with the CLT group on ADOS severity scores (Communication, Social and Total), on GMDS Social domain and on VABS Communication and Social domains. PECS-related gains on the VABS Social domain and on specific social-communicative measures coded during free-play, i.e. frequency of joint attention and initiation, and duration of cooperative play, were stable after 1-year follow-up. Cooperative play continued to improve on follow-up with respect to both post- and pre-treatment assessment. CONCLUSIONS & IMPLICATIONS: These findings demonstrated that PECS training can promote long-term enhancement of specific socio-communicative skills in children with autism.

Motor imagery in Asperger syndrome: testing action simulation by the hand laterality task.

Asperger syndrome (AS) is a neurodevelopmental condition within the Autism Spectrum Disorders (ASD) characterized by specific difficulties in social interaction, communication and behavioural control. In recent years, it has been suggested that ASD is related to a dysfunction of action simulation processes, but studies employing imitation or action observation tasks provided mixed results. Here, we addressed action simulation processes in adolescents with AS by means of a motor imagery task, the classical hand laterality task (to decide whether a rotated hand image is left or right); mental rotation of letters was also evaluated. As a specific marker of action simulation in hand rotation, we assessed the so-called biomechanical effect, that is the advantage for judging hand pictures showing physically comfortable versus physically awkward positions. We found the biomechanical effect in typically-developing participants but not in participants with AS. Overall performance on both hand laterality and letter rotation tasks, instead, did not differ in the two groups. These findings demonstrated a specific alteration of motor imagery skills in AS. We suggest that impaired mental simulation and imitation of goal-less movements in ASD could be related to shared cognitive mechanisms.

Social-communicative effects of the Picture Exchange Communication System (PECS) in autism spectrum disorders.

BACKGROUND: The Picture Exchange Communication System (PECS) is a common treatment choice for non-verbal children with autism. However, little empirical evidence is available on the usefulness of PECS in treating social-communication impairments in autism. AIMS: To test the effects of PECS on social-communicative skills in children with autism, concurrently taking into account standardized psychometric data, standardized functional assessment of adaptive behaviour, and information on social-communicative variables coded in an unstructured setting. METHODS & PROCEDURES: Eighteen preschool children (mean age = 38.78 months) were assigned to two intervention approaches, i.e. PECS and Conventional Language Therapy (CLT). Both PECS (Phases I-IV) and CLT were delivered three times per week, in 30-min sessions, for 6 months. Outcome measures were the following: Autism Diagnostic Observation Schedule (ADOS) domain scores for Communication and Reciprocal Social Interaction; Language and Personal-Social subscales of the Griffiths' Mental Developmental Scales (GMDS); Communication and Social Abilities domains of the Vineland Adaptive Behavior Scales (VABS); and several social-communicative variables coded in an unstructured setting. OUTCOMES & RESULTS: Results demonstrated that the two groups did not differ at Time 1 (pre-treatment assessment), whereas at Time 2 (post-test) the PECS group showed a significant improvement with respect to the CLT group on the VABS social domain score and on almost all the social-communicative abilities coded in the unstructured setting (i.e. joint attention, request, initiation, cooperative play, but not eye contact). CONCLUSIONS & IMPLICATIONS: These findings showed that PECS intervention (Phases I-IV) can improve social-communicative skills in children with autism. This improvement is especially evident in standardized measures of adaptive behaviour and measures derived from the observation of children in an unstructured setting.

A familial inverted duplication/deletion of 2p25.1-25.3 provides new clues on the genesis of inverted duplications.

We studied a family in which the same 10 Mb inverted duplication of 2p25.3-p25.1 segregates in two children and their father, all showing a trisomy phenotype. As FISH analysis demonstrated that the duplication was inverted, we suspected that a contiguous terminal deletion was also present, according to the classical inv dup del type of rearrangements. Although FISH with 2p and 2q subtelomeric probes gave normal results, 100 kb resolution array-C/GH (aCGH) showed that, beside the duplication, a 273 kb deletion was also present. The presence of a single-copy region between the deleted and duplicated regions was further suspected through high-resolution aCGH analysis (approximately 20 kb), although only one informative spot having a normal log ratio was detected. The precise structure of the rearrangement was re-defined by real-time PCR and breakpoint cloning, demonstrating the presence of a 2680 bp single-copy sequence between deleted and duplicated regions and the involvement of a simple repeat with the potential for forming a non-B DNA structure. The rearrangement was not mediated by segmental duplications or short inverted repeats, and the double-strand break might have been repaired by non-homologous end joining or microhomology-mediated intrastrand repair. These data highlight the fact that concomitant deletions associated with inverted duplications are very likely to be more frequent than classical cytogenetic methods alone have been able to demonstrate. The phenotypic effects of the trisomy and of the terminal 2p deletion are discussed.