Parent Evaluation of Developmental Status (PEDS) in screening: The Thai experience.

BACKGROUND: Parent Evaluation of Developmental Status (PEDS) is a feasible developmental screening tool but it is not commonly used in Thailand. To examine the potential of PEDS as a screening tool, PEDS was implemented in well-child visits to identify the prevalence of developmental problems, characteristic parental concerns and comments, and to compare it with pediatrician developmental evaluation using Parent Evaluation of Developmental Status: Developmental Milestones, assessment level (PEDS: DM-AL). METHODS: Participants were 266 children at the 9, 18 and 30 month health checkups as well as their parents. The PEDS questionnaire (Thai version) was first used for parents, and then the children were evaluated by pediatricians using PEDS: DM-AL. RESULTS: Using PEDS, 12% and 34% of children were classified as high and moderate risk for developmental and social-emotion disorders. The most common concerns were behavioral problems, social-emotion problems and expressive language. On PEDS: DM-AL, 24% of children had delay in at least one domain of development. When PEDS screening was compared with PEDS: DM-AL, being in the PEDS high-risk group had 27.7% sensitivity and 93.0% specificity. If being in the moderate or high-risk group was used instead, the sensitivity was enhanced to 67.7%, with 60.7% specificity. CONCLUSIONS: Implementation of PEDS in well-child visits could enhance early detection of developmental problems, but many Thai parents were unable to mention their concerns about delayed abilities in the correct PEDS question. Therefore, to ensure higher sensitivity, criteria for referral should be adjusted and a second stage developmental evaluation may be incorporated with PEDS.

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).

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.

Attention-deficit/hyperactive-impulsive disorder symptoms among grade 1 students with reading disorder in Thailand.

BACKGROUND: Reading disorder is the most common comorbid condition with attention-deficit/hyperactive-impulsive disorder (ADHD) in school-aged children. PURPOSE: This study compared symptoms of ADHD among children in grade 1 at risk of reading disorder with children not at risk. METHODS: This cross-sectional study included 703 students in grade 1 aged 6-8 years from 8 schools in Pathumthani Province, Thailand, in 2019. Reading disorder was assessed using tools developed by Vibulpatanavong and Evans for Thai teachers, whereas the Thai parent and teacher versions of the Swanson, Nolan, and Pelham IV Rating Scale (SNAP-IV) was used to evaluate ADHD symptoms. Demographic data were collected from parents using a self-reported questionnaire. RESULTS: Among the 703 students with almost equal number of male (n=350) and female (n=353), and the average age of 6.56±0.57 years, 95 (13.51%) were classified (significantly male) at risk of reading disorder. The mean SNAP-IV scores of children with reading disorder reported by parents and teachers (20.23±10.95 and 20.75±15.08, respectively) were significantly higher than those of neurotypical children (16.04 ±8.59 and 9.00±10.14, respectively, P<0.05). Of the 95 students with reading disorder reported by parents and teachers, 29 (30.53%) and 20 (21.05%) respectively, were defined as having ADHD according to the standard cutoff SNAP-IV scores, which were significantly higher than 608 neurotypical students at 108 (17.76%) and 20 (5.59%) (P<0.05). The odds ratios of children with reading disorder having ADHD symptoms according to teacher reports were 3.32 (95% confidence interval [CI], 1.14-9.67; P<0.05), 3.75 (95% CI, 1.60-8.79; P<0.05), and 4.41 (95% CI, 1.20-16.15; P<0.05) for inattentive, hyperactive, and combined presentations, respectively. CONCLUSION: Grade 1 students with reading disorder had a significantly higher prevalence of ADHD symptoms than neurotypical students. Therefore, children with reading disorders should undergo ADHD assessments and receive proactive intervention.

Effects of mirror neurons stimulation on motor skill rehabilitation in children with cerebral palsy: a clinical trial.

OBJECTIVE: The authors aimed to compare the motor function measured by Gross Motor Function Measure (GMFM-66) between mirror neurons stimulation based VCD program at home and conventional physical therapy in children with cerebral palsy for two months. MATERIAL AND METHOD: A randomized controlled trial was performed with thirty children with spastic diplegia aged 2-10 years in Thammasat university hospital and Rajanukul institue. They were randomly assigned to receive either the mirror neurons stimulation based VCD program practice at home (experimental group) or the conventional physical therapy (control group) for two months. Both groups were measured the motor function by GMFM-66 at entry, the first month and the end of the second month. Analysis of covariance was used to compare mean changes of GMFM-66 scores between both groups at the second month after adjusted for the baseline level. RESULTS: A total of 30 children with cerebral palsy, aged 2.2-9.5 years (mean age 5.9 +/- 2.2 years). The mean changes of the GMFM scores in experimental group were slightly higher than those in the control group of 2.1 (95% CI: -2.3, 6.5) at the second month after adjusted for the baseline level. The mean GMFM scores were significantly improved in all dimensions except lying and rolling dimension, at the first and second month when compared to the baseline level in both groups. CONCLUSION: This pilot study demonstrated the mirror neurons stimulation based VCD program can improve motor function, at least, as much as the conventional physical therapy.

Chromosomal microarray analysis in a cohort of underrepresented population identifies SERINC2 as a novel candidate gene for autism spectrum disorder.

Chromosomal microarray (CMA) is now recognized as the first-tier genetic test for detection of copy number variations (CNVs) in patients with autism spectrum disorder (ASD). The aims of this study were to identify known and novel ASD associated-CNVs and to evaluate the diagnostic yield of CMA in Thai patients with ASD. The Infinium CytoSNP-850K BeadChip was used to detect CNVs in 114 Thai patients comprised of 68 retrospective ASD patients (group 1) with the use of CMA as a second line test and 46 prospective ASD and developmental delay patients (group 2) with the use of CMA as the first-tier test. We identified 7 (6.1%) pathogenic CNVs and 22 (19.3%) variants of uncertain clinical significance (VOUS). A total of 29 patients with pathogenic CNVs and VOUS were found in 22% (15/68) and 30.4% (14/46) of the patients in groups 1 and 2, respectively. The difference in detected CNV frequencies between the 2 groups was not statistically significant (Chi square = 1.02, df = 1, P = 0.31). In addition, we propose one novel ASD candidate gene, SERINC2, which warrants further investigation. Our findings provide supportive evidence that CMA studies using population-specific reference databases in underrepresented populations are useful for identification of novel candidate genes.

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.

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.