Longitudinal Case-Control Study of Imitation in Younger Siblings of Children with Autism Spectrum Disorder.

Background: Siblings of children with autism spectrum disorders (ASD) have higher prevalence of ASD with a recurrence of 19%. Children with ASD demonstrate significant impairment in all types of imitative skills. Imitation is markedly developed in the first few years of life; therefore, a study of imitation in younger siblings in this period may reveal early deviation. Objective: To study the development of imitation skills from 9- to 18-months, specifying types of imitation, in siblings of children with ASD compared with typically developing children. Method and Material: A longitudinal case-control study was conducted on eight siblings of children with ASDs and nineteen typically developing children who were age- and gender-matched. Data collection consisted of parental recording of emerging imitative abilities and structured direct observation of imitative skills at 9, 12 and 18 months. Three types of imitative skills were targeted including vocal, object and gesture imitation. Results: The development of vocal imitation in siblings of children with ASD between 12 to 18 months was delayed in comparison with typically developing children with significant statistical difference at 18 months. Object and gesture imitations were not significantly different between the two groups. Conclusion: Siblings of children with ASDs had some delays in vocal imitation skills at the age of 12 to 18 months, compared with typically developing children.

A new structured interview for children with autism spectrum disorder based on the DSM-IV.

BACKGROUND: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder in children. The clinical spectrum of ASD includes autism, childhood disintegrative disorder Asperger syndrome and pervasive developmental disorder not otherwise specified (PDD-NOS). Although the DSM-IVcriteria are well acceptedforASD diagnosis, there are some known limitations for clinicians. The most important issue is lack'ofspecific age-appropriate items in each domain. Thus, the DSM-IVneeds some modifications in order to be appropriate for clinical use. OBJECTIVE: To develop a structured interview for children based on the DSM-IVdiagnostic criteria ofautism and PDD-NOS. MATERIAL ANDMETHOD: From June 2006 to December 2008, 140 Thai children, 121 boys and 19 girls, already diagnosed with ASD, were recruited through the child development clinics of Ramathibodi and Thammasat University Hospitals in Thailand. A 26-item structured interview was developed with scoring according to the DSM-IVdiagnostic criteria for autism andPDD- NOS. To test the accuracy of the structured interview and its reliability, 32 children with ASD were selected and interviewed by four clinicians using the new instrument. One clinician interviewed the parents or caregivers, while three others independently took notes and observed the play behavior of the children. All items from the structured interview as scored by each clinician were compared using inter-rater agreement statistics (Kappa). All of the original 140 patients were then clinically diagnosed again using the structured interview and the results were compared with the initial diagnoses. RESULTS: Ofthe 140patients originally diagnosed with ASD, 110 and 30patients were finally diagnosed with the new interview as having autism and PDD-NOS, respectively. The initial diagnoses from 15 cases (10.7%) were changed according to the structured interview Inter-rater reliability among the four clinicians showed a good level ofagreement (Kappa = 0.897) with statistical significance (p<0.001). The authors only compared the items in the structured interview between the autism and PDD-NOSgroups from 105 cases aged 2-5 years (79 cases with autism and 26 cases with PDD-NOS) because there were only 4 cases with PDD-NOS in the other age groups. Highly significant differences (p<0.001) in clinical items between patients with autism and patients with PDD-NOS from the final diagnoses were noted in 6 of 8 items in the category of restricted, repetitive and stereotyped patterns ofbehavior, interests and activities, which were more common in the autism group than the PDD-NOS group. In addition, the autism group had higher frequencies of using finger-pointing to indicate interest rather than verbalization, and idiosyncratic language, than the PDD-NOS group. CONCLUSION: The newly developed structured interview for Thai children with ASD had a high level ofinterrater reliability between four clinicians. However, most children tested using this structured interview were 2-5years ofage, and the study did not include non-autistic groups. The application ofthis structured interview needs further study with a wider variety ofcases, such as ASD cases from different age groups, children with delayed development and normal children.

A case with a ring chromosome 13 in a cohort of 203 children with non-syndromic autism and review of the cytogenetic literature.

Autistic spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by impairments of social interaction, communication and restricted, repetitive and stereotyped patterns of behavior, interests and activities. Frequencies of chromosomal abnormalities in cohorts of individuals with ASD varying between 1.2 and 28.6% have been reported. In this study, we evaluated 203 Thai children who met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), for autistic disorder or pervasive developmental disorder not otherwise specified (PDD-NOS), and who had neither major dysmorphic features nor CGG repeat expansions of the FMR1 gene. A routine G-banding chromosome analysis was performed at a minimum of ISCN 400-550 bands. A chromosomal abnormality was observed in one child (0.5%), a 41-month-old boy with a ring chromosome 13 detected by G-banding analysis and subsequently confirmed by FISH. SNP microarray analysis detected a 2.11-Mb deletion of chromosome 13q34, encompassing 23 genes. The MCF2L and UPF3A genes are among those genes that may explain the autistic features in our case. To the best of our knowledge, only one autistic case with a ring chromosome 13 has been previously reported. In this article, we also systemically reviewed 21 studies that utilized a conventional cytogenetic method to detect chromosomal abnormalities in patients with ASD. When we summed all cases with chromosomal abnormalities, including the case from our study, the frequency of chromosomal abnormalities detected by conventional cytogenetics in patients with ASD was 3.2% (118/3,712).

Mutation screening of the neurexin 1 gene in thai patients with intellectual disability and autism spectrum disorder.

AIM: Neurexin 1 has two major protein isoforms using alternative promoters, coding for the alpha-neurexin 1 (α-NRXN1) and beta-neurexin 1 (ß-NRXN1) genes. This study is to explore the possibility that variants of the NRXN1 gene predispose to intellectual disability (ID) and autism spectrum disorder (ASD). METHODS: The coding regions in 24 exons and exon-intron boundaries of the NRXN1 gene were investigated in 115 Thai patients with ID and ASD by direct DNA sequencing. RESULTS: Nine novel variants of the NRXN1 gene were identified. Four novel variants were found in the ß-NRXN1 gene, one variant of six GGC repeats in exon 1, and three variants at the 5'UTR. Five novel variants were identified in the α-NRXN1 gene, four intronic variants and one missense variant in exon 14 (c.2713T>A or p.F905I). CONCLUSION: Mutation screening of the NRXN1gene in patients with ID and ASD may be useful to identify potential variants predisposing to ID and ASD. However, further studies utilizing protein functional analysis of the novel variants are required for a more definite conclusion.

Language development among the siblings of children with autistic spectrum disorder.

Language development in 32 preschool siblings (aged 2-6 years) of children with diagnosed autistic spectrum disorder (ASD) was compared with that of a control group of 28 typical preschool children. Groups were matched by siblings' age, gender, maternal educational level and family income. The mean ages of the siblings group and the control group were 4.2 and 4.4 years. Eight of the siblings had delayed language development, of whom three received a diagnosis of developmental language disorder (DLD) and one of ASD. The sibling with ASD and two of those with DLD were excluded; the remaining 29 siblings and the controls were administered the Stanford-Binet IV. Verbal IQs of siblings were not significantly different from the control group. Siblings of children with ASD associated with intellectual impairment ('mental retardation' (MR) in Thailand) had significantly lower verbal IQ scores than siblings of children with ASD but without MR.

Epidemiology of enuresis among school-age children in Thailand.

Enuresis is a very common developmental problem in young children. The aims of this study were to estimate the prevalence of enuresis in school-age children, to determine the factors associated with nocturnal enuresis, and to evaluate the parental strategies for managing enuresis. A randomly selected cross-sectional population-based study was conducted in eight elementary schools in Bangkok, Thailand. A total of 3453 parents of children aged 5 through 15 years completed the questionnaires. The overall response rate to the questionnaire was 70%. The prevalence of enuresis was 4.2% and that of nocturnal enuresis was 3.9%. The prevalence declined with increasing age from 10%, 5.3%, 3%, and 1.2% at ages 5, 7, 10, and 12 years, respectively. There was no enuretic child at ages 13 through 15 years. The prevalence of bed-wetting was slightly more frequent in females than males. Nocturnal enuresis was also found to be significantly associated with the history of encopresis and positive family history of enuresis. There was no significant associated with parental education, birth order, socioeconomic status, diaper use, toilet training, and behavioral and school problems. Behavioral techniques mostly used by parents for management of their children with bed-wetting were ensuring that the child voids before bedtime (72.9%), waking the child up at night to void (61.8%), and evening water intake restriction (28.5%). The overall prevalence rate of nocturnal enuresis in Bangkok school-age children is lower than that of many previous studies reported from other countries. The significant differences in the prevalence reported by other countries' studies attributed to the criteria selection for ranges of age, definition of enuresis, genetic predisposition, and traditional and cultural background.