Ramathibodi Language Development Questionnaire: A Newly Developed Screening Tool for Detection of Delayed Language Development in Children Aged 18-30 Months.

OBJECTIVE: To develop a parental questionnaire for screening children with delayed language development in primary care settings. MATERIAL AND METHOD: Ramathibodi Language Development (RLD) questionnaire was developed and completed by groups of 40 typically developing children age 18 to 30 months old and 30 children with delayed language development. RESULTS: The mean score was significantly lower in the delay language group (6.7 ± 1.9), comparing with the typically developing group (9.6 ± 0.7). The optimal ROC curve cut-off score was 8 with corresponding sensitivity and specificity were 98% and 72%, respectively. The corresponding area under the curve was 0.96 (95% CI = 0.92-0.99). CONCLUSION: The RLD questionnaire was the promising language developmental screening instrument that easily utilized in well-child examination settings.

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).

Translation and validation of the Children's Communication Checklist to evaluate pragmatic language impairment in Thai children.

BACKGROUND: The Children's Communication Checklist (CCC) was developed to provide an assessment of domains of language impairment in children, particularly the pragmatic domain. This study examined the effectiveness of the CCC-Thai version in discriminating children with autism spectrum disorders (ASD) from typically developing children. METHODS: The parents of two groups of 50 children aged 4-6 years, one with clinically ascertained ASD, and one with typical development, completed the CCC-Thai version. RESULTS: The mean pragmatic composite score was significantly lower in the ASD group (124.6) than in the typical development group (142). The optimal receiver operating characteristic curve cut-off score was found to be identical to the original English version (132). Corresponding sensitivity and specificity were 94% and 86%, respectively. The positive predictive value and the negative predictive value were 87% and 93%, respectively. The corresponding area under the curve was 0.95 (95% confidence interval: 0.91-0.99). CONCLUSION: The CCC-Thai version is a promising instrument to assess pragmatic language impairment in Thai children.

Impaired picture sequencing ability in children with premature birth.

BACKGROUND: Children born preterm are at increased risk for executive dysfunction, which affects learning outcomes. Picture sequencing ability is considered as executive function (EF) that requires skills in working memory and organizing the pictures. Children born preterm might have difficulties in these skills. The present study aimed to develop practical Picture Sequencing test (PS test) and examine the sequencing ability in preterm children comparing with term children. MATERIAL AND METHOD: The PS test was developed to assess the child's ability to arrange pictures into a sequence. It consisted of three conditions, which were daily activities, social interaction routines, and feeling expressions. Each story had four cartoon styles cards. The child had to rearrange picture cards into the correct sequence positions. Thirty preterm children aged five to six years with gestational ages of 32 weeks and birth weights of < 1,500 grams, and thirty-five term children matched age, gender child 's education, parental education, and socioeconomic status were performed the PS test. The total scores were compared between the preterm group and the term group. RESULTS: The PS test scores on the daily activities domain of the preterm and term group were 18 and 25 (p = 0.03), respectively. The scores on the social interaction routines domain ofthe preterm and term group were 20 and 28 (p = 0.01) and the scores on the feeling expression domain were 18.5 and25 (p = 0.03), respectively. There was no significant correlation between perinatal complications and the PS test scores. CONCLUSION: The preterm children with IQs in the average range showed impairment in sequencing ability compared with the term children. The results underline the need for follow-up care with more comprehensive assessment of EF.

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.

Effect of Chronic Rhinitis Treatment in Children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: The purpose of this study is to examine the effect of chronic rhinitis treatment on attention-deficit/hyperactivity disorder (ADHD) symptoms in children with ADHD. METHODS: Children and adolescents with ADHD were screened for chronic rhinitis symptoms. Participants with positive chronic rhinitis screening underwent the skin prick test and received rhinitis treatment for 3 months. All participants were evaluated using the parent's and teacher's Vanderbilt ADHD rating scales, total nasal symptom score, and Quality of Life Questionnaire (OSA-18) for pediatric obstructive sleep apnea at pretreatment and posttreatment. RESULTS: Overall, 140 children and adolescents with ADHD were enrolled and screened for chronic rhinitis. Fifty-four children and adolescents with positive screening results underwent the skin prick test and received rhinitis treatment. After 3 months of treatment, inattentive, hyperactive/impulsive, and total ADHD symptom scores were significantly decreased as reported by parents ( p = 0.031 to <0.001) and teachers ( p = 0.001 to <0.001) compared with those before treatment. A subgroup analysis also showed improvement in ADHD symptoms as reported by parents and teachers in the allergic and nonallergic rhinitis groups. Pearson's correlation coefficient analyses showed positive correlations between improvement in the ADHD symptom scores reported by parents and improvement in the quality of life related to sleep problems from the OSA-18 questionnaire (r = 0.377-0.387). CONCLUSION: Treating chronic rhinitis can improve ADHD symptoms in children and adolescents with ADHD. Pediatricians should be aware of and treat chronic rhinitis to maximize ADHD symptom control.

Effect of Iron Supplementation in Children with Attention-Deficit/Hyperactivity Disorder and Iron Deficiency: A Randomized Controlled Trial.

OBJECTIVES: To determine the effectiveness of combined iron supplementation and methylphenidate treatment on attention-deficit/hyperactivity disorder (ADHD) symptoms in children/adolescents with ADHD and iron deficiency compared with methylphenidate alone. METHODS: In total, 116 children/adolescents with ADHD were screened for iron deficiency. Participants who exhibited iron deficiency were randomized into 2 groups (ferrous supplementation vs placebo). Vanderbilt ADHD rating scales were completed by parents and teachers at prestudy and poststudy periods. Student's t tests were used to determine improvements of Vanderbilt scores between the groups. RESULTS: Among 116 children who participated in this study, 44.8% (52/116) met the criteria for iron deficiency. Of the total 52 participants with iron deficiency, 26 were randomized to the ferrous group and 26 to the placebo group. Most participants in each group had been prescribed short-acting methylphenidate twice daily in the morning and at noon. After a 12-week study period, total parents' Vanderbilt ADHD symptom scores showed a significant improvement between the groups (mean decrement = -3.96 ± 6.79 vs 0 ± 6.54, p = 0.037). However, teachers' Vanderbilt ADHD symptom scores showed no difference between the groups. CONCLUSION: Children with ADHD and iron deficiency being on methylphenidate and iron supplementation had shown improvement of ADHD symptoms that were reported by parents.

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.

Emergent Literacy in Thai Preschoolers: A Preliminary Study.

OBJECTIVE: To investigate emergent literacy skills, including phonological awareness when presented with an initial phoneme-matching task and letter knowledge when presented with a letter-naming task in Thai preschoolers, and to identify key factors associated with those skills. METHODS: Four hundred twelve typically developing children in their final kindergarten year were enrolled in this study. Their emergent reading skills were measured by initial phoneme-matching and letter-naming tasks. Determinant variables, such as parents' education and teachers' perception, were collected by self-report questionnaires. RESULTS: The mean score of the initial phoneme-matching task was 4.5 (45% of a total of 10 scores). The mean score of the letter-naming task without a picture representing the target letter name was 30.2 (68.6% of a total of 44 scores), which increased to 38.8 (88.2% of a total of 44 scores) in the letter-naming task when a picture representing the target letter name was provided. Both initial phoneme-matching and letter-naming abilities were associated with the mother's education and household income. Letter-naming ability was also influenced by home reading activities and gender. CONCLUSION: This was a preliminary study into emergent literacy skills of Thai preschoolers. The findings supported the importance of focusing on phonological awareness and phonics, especially in the socioeconomic disadvantaged group.

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.

Parents' Evaluation of Developmental Status (PEDS) in Screening for Developmental Delay in Thai Children Aged 18-30 Months.

The PEDS-Thai is a developmental screening tool. We studied its diagnostic performance among 137 Thai children (48.9%) aged 18-30 month. It had a sensitivity of 92.8% and a specificity of 49.2%. The positive and negative likelihood ratios were 1.82 and 0.14 when compared with clinical diagnosis and diagnostic tool, the Mullen Scales of Early Learning.

Prevalence and clinical characteristics of dyslexia in primary school students.

BACKGROUND: Dyslexia is the most common subtype of learning disabilities with a prevalence ranging from 5-10 per cent. The central difficulty in dyslexia is the phonological awareness deficit. The authors have developed a screening test to assess the reading ability of Thai primary school students. OBJECTIVE: 1. To study the prevalence of dyslexia in first to sixth grade students at Wat Samiannaree School. 2. To study the clinical characteristics such as sex, neurological signs, verbal intelligence and comorbid attention deficit hyperactive disorder (ADHD) of the dyslexia group. METHOD: A total of 486 first to sixth grade students were administered "Raven's progressive matrices test" for estimation of intellectual functioning. Those who scored below the fifth percentile were labeled as mental retardation and excluded from the study. The students' reading ability was evaluated by 3 steps; first by classroom teachers using some items of the screening test, second by the researchers examining some more items individually, and third by the special educator assessing more details in reading and phonology. The students who had a reading ability two-grade levels below their actual grades and impairment in phonology were diagnosed with dyslexia. RESULTS: The prevalence of dyslexia and probable dyslexia were found to be 6.3 per cent and 12.6 per cent, respectively. The male to female ratio of dyslexia was 3.4:1. The dyslexia group had significantly lower Thai language scores than those of the normal group (p < 0.05). All of the dyslexia group had a normal grossly neurological examination but 90 per cent showed positive soft neurological signs. Mean verbal intellectual quotient score in the dyslexia group assessed by using Wechsler Intelligence Scales for Children--Revised was 76 +/- 7. The comorbid ADHD was 8.7 per cent in the dyslexia group. CONCLUSION: Dyslexia was a common problem among primary school students in this study. Further studies in a larger population and different socioeconomic statuses are required to determine the prevalence of dyslexia in the general population. The authors suggest evaluating the reading ability carefully by using a test that can detect phonological awareness deficit in all children who have learning problems.

Effect of oral vitamin E supplementation in children with cholestasis.

OBJECTIVE: Malabsorption and deficiency of vitamin E are common consequences of chronic cholestasis. The objective of this study was to determine vitamin E status by using plasma vitamin E/total lipid ratio (E/L) in children with cholestasis during supplementation with 20 IU/kg/day and 100 IU/kg/day of oral vitamin E capsule, and 50 IU/kg/day of cold water soluble form (CWSIF) of vitamin E. METHOD: Children with cholestasis who were being supplemented with 20 IU/kg/day of oral vitamin E capsule (dl-alpha-tocopherol) were enrolled into this study. After initial evaluation for vitamin E status and liver function, doses of oral vitamin E supplementation were increased to 100 IU/kg/day for 1 month. Then, supplementation was switched to 50 IU/kg/day of CWS/F vitamin E for 1 month. Vitamin E status was assessed by using plasma E/L after each period of supplementation. RESULTS: Eleven children with biliary atresia, aged between 2 and 18 months, were studied. Their median weight standard deviation score (SDS) was -1.35 and median height SDS was -1.26. The medians of serum direct bilirubin and total bilirubin were 6.5 and 12.9 mg/dl, respectively. Only 2 and 3 out of 9 children had plasma E/L above normal cut-off levels during supplementation with 20 and 100 IU/kg/day of vitamin E capsule, respectively. Additionally, 4 of 9 children had plasma E/L above normal cut-off level after one month's supplementation with 50 IU/kg/day of CWS/F vitamin E. All the responders had serum bilirubin levels less than 4 mg/dl while the remainder with serum direct bilirubin level more than 4 mg/dl had their plasma E/L below normal cut-off levels in spite of any vitamin E supplementation. CONCLUSION: Oral vitamin E supplementation with 20 IU/kg/day and 100 IU/kg/day of vitamin E capsule and with 50 IU/kg/day of CWS/F vitamin E were able to normalize vitamin E status in a few cholestatic children who had serum direct bilirubin levels less them 4 mg/dl. In cases of serum direct bilirubin more than 4 mg/dl, neither of vitamin E supplementations was able to correct the vitamin E deficiency status.

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.

Comparison of mental health symptoms between children attending developmental/behavioural paediatric clinics and child and adolescent mental health service.

AIM: Australian paediatricians are being referred many children with severe and complex behavioural presentations. Australian paediatricians are being referred many children with severe and complex behavioural presentations. The aim of this study was to compare patients seen in the developmental/behavioural paediatric clinic (DBP) with those seen in the community child and adolescent mental health service (CAMHS) of a paediatric teaching hospital. We hypothesised that the burden of emotional-behavioural symptoms of children referred to these two services would be similar. METHOD: The Strengths and Difficulties Questionnaire was completed by parents of children seen in both the DBP and the CAMHS of a paediatric teaching hospital over a 6-month period. The self-report version was completed by patients aged over 11 years. Data were compared both continuously and categorically, for total scores and subscale scores. RESULTS: For patients aged 4-10 years, the total scores were higher for the CAMHS (mean=20.4) than the DBP (mean=16.6) sample (P<0.001). For patients aged 11-17 years, there was no difference between the groups in either the parent report total scores (CAMHS 19.4; DBP 19.3, P=0.92) or the self-report total scores (CAMHS 17.5; DBP 15.7, P=0.11). CONCLUSION: Children referred to a DBP clinic had a comparable burden of emotional/behavioural symptoms to those referred to a CAMHS service, although the degree of impairment was higher in the CAMHS sample. The complexity and severity of clinical work undertaken in DBP services needs to be taken into account in paediatric training, and in the broad planning of child and adolescent mental health service delivery.