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Objectives: This study validated the Japanese version of the Attention‐Deficit/Hyperactivity Disorder‐Rating Scale‐5 (ADHD‐RS‐5) and the Disruptive Behavior Disorders Rating Scale. We extended the ADHD‐RS‐5 by adding the oppositional defiant disorder and conduct disorder subscales to compare the two rating scales psychometrically. Methods: We examined the internal consistency, test‐retest reliability, construct validity and criterion validity of the two rating scales in 135 Japanese outpatients aged 6–18 years. Results: The internal consistency and test‐retest reliability were good for all the subscales of the two rating scales except for the conduct disorder subscale of the ADHD‐RS‐5 extended. Good construct validity was revealed by expected correlational patterns between subscales from the two rating scales and the Children Behavior Checklist. The criterion validity was good for all the subscales of the two rating scales rated by parents, while teacher‐ratings revealed substantially lower predictive ability for all the subscales. Agreement between parent‐ and teacher‐ratings of the two rating scales was generally moderate and using predictive ratings alone of both ratings showed the best predictive ability among the integration methods examined. Conclusion: The two rating scales have sound psychometric properties and will aid in screening and severity assessment of externalizing disorders in Japanese clinical settings. [ABSTRACT FROM AUTHOR]

AFF3 at 2q11.2 encodes the nuclear transcriptional activator AF4/FMR2 Family Member 3. AFF3 constitutes super elongation complex like 3, which plays a role in promoting the expression of genes involved in neurogenesis and development. The degron motif in AFF3 with nine highly conserved amino acids is recognized by E3 ubiquitin ligase to induce protein degradation. Recently, AFF3 missense variants in this region and variants featuring deletion including this region were identified and shown to cause KINSSHIP syndrome. In this study, we identified two novel and one previously reported missense variants in the degron of AFF3 in three unrelated Japanese patients. Notably, two of these three variants exhibited mosaicism in the examined tissues. This study suggests that mosaic variants also cause KINSSHIP syndrome, showing various phenotypes. [ABSTRACT FROM AUTHOR]

In March 2020, many schools were closed to prevent the spread of COVID-19 in Japan, and it is predicted that many children, especially those with neurodevelopmental disorders (NDDs), will be affected emotionally and behaviorally. Here, we examined the impact of school closures due to COVID-19 on school-aged children with NDDs using the Child Behavior Checklist. Totally, data on 121 children diagnosed with autism spectrum disorder, attention-deficit hyperactivity disorder, and/or intellectual disorder were analyzed and it was found that externalizing and aggressive behavior increased in all NDDs, regardless of the type of diagnosis. A clear prospect is important for children with NDDs children to lead a stable life, and more generous supports for children with NDDs and their families are needed. [ABSTRACT FROM AUTHOR]

The article presents the case study of two cases of extended-release guanfacine (GXR) overdose in children. It is reported that Guanfacine, an alpha-2 agonist, is commonly used to treat attention-deficit hyperactivity disorder (ADHD) in Japan. It is further noted that the cases involve a five year old male with ADHD and autism spectrum disorder (ASD) and a 15 year old boy with ADHD and oppositional defiant disorder (ODD).

Although genetic factors are involved in the etiology of autism spectrum disorder (ASD), the significance of genetic analysis in clinical settings is unclear. Forty-nine subjects diagnosed with non-syndromic ASD were analyzed by microarray comparative genomic hybridization (CGH) analysis, whole-exome sequencing (WES) analysis, and panel sequencing analysis for 52 common causative genes of ASD to detect inherited rare variants. Genetic analysis by microarray CGH and WES analyses showed conclusive results in about 10% of patients, however, many inherited variants detected by panel sequencing analysis were difficult to interpret and apply in clinical practice in the majority of patients. Further improvement of interpretation of many variants detected would be necessary for combined genetic tests to be used in clinical settings. [ABSTRACT FROM AUTHOR]

Aim: We evaluated combined genetic analyses with targeted next-generation sequencing (NGS), multiplex ligation probe amplification (MLPA) of Jagged1 (JAG1) genes and microarray comparative genomic hybridisation (CGH) in subjects with Alagille syndrome, incomplete clinical features of Alagille syndrome and biliary atresia.Methods: Subjects recruited from April 2013 to December 2015 underwent a targeted NGS analysis, including JAG1 and Notch homolog 2 (NOTCH2). If no mutations were detected in JAG1 or NOTCH2, or if copy number variations were suggested by the NGS analysis, we performed an MLPA analysis of JAG1. We also performed a microarray CGH analysis with whole-exon deletion detected by the MLPA analysis.Results: We analysed 30 subjects with Alagille syndrome, nine with incomplete Alagille syndrome and 17 with biliary atresia and detected pathogenic mutations in JAG1 or NOTCH2 in 24/30 subjects with Alagille syndrome and in 4/9 subjects with incomplete Alagille syndrome. No pathogenic mutations were detected in subjects with biliary atresia. The frequency of JAG1 mutations was as follows: single nucleotide variants (51.9%), small insertion or deletion (29.6%) and gross deletion (18.5%).Conclusion: Combined genetic analyses achieved efficient diagnostic yields for subjects with Alagille syndrome and incomplete Alagille syndrome. [ABSTRACT FROM AUTHOR]

Bainbridge-Ropers syndrome (BRPS) is characterized by severe developmental delay, feeding problems, short stature, characteristic facal appearance including arched eyebrows and anteverted nares, and ulnar deviation of the hands. BRPS is caused by a heterozygous mutation in the additional sex combs-like 3 ( ASXL3) gene. We describe a patient with severe developmental delay, feeding problems, short stature, autism, and sleep disturbance with a heterozygous de novo splicing mutation in the ASXL3 gene. Reported disease-causing mutations in ASXL3 are located mostly in the first half of exon 11, analogous to ASXL1 mutations of which result in Bohring-Opitz syndrome (BOS). Our findings suggest that the expression of the truncated ASXL3 protein, including ASXN and ASXH domains, give rise to BRPS, which is distinct from but overlaps with BOS. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was published in May 2013. Autism spectrum disorder (ASD) has been structured for the three subtypes of pervasive developmental disorder (PDD), but the number of impairment in social and communication dimension is not stated. Methods: The subjects were 68 children who visited the Department of Psychology and Development at Nagoya City University Hospital for the first time between the ages of 6 and 15 years old. We retrospectively re-examined the subjects using DSM-IV-TR criteria and DSM-5 criteria with two rules (two of three and one of three on the social and communication dimension) and examined the concordance rate. Results: Forty subjects were diagnosed with PDD, and 28 were not. The mean PDD subject age was 9.4 years, and mean IQ was 84.0 on the Wechsler Intelligence Scale for Children III or 62.7 on the Tanaka-Binet test. Twenty-seven (68%) of the PDD subjects were classified with ASD using DSM-5 criteria when the two of three rule was applied, while 32 (80%) were classified with ASD when the one of three rule was applied. All subjects without PDD were not diagnosed with ASD on DSM-5 criteria. Conclusion: DSM-5 criteria may exclude high functioning and older subjects from ASD because they tend to be atypical. The diagnostic procedure for DSM-5 criteria is ambiguous, especially in high functioning subjects and those diagnosed at an older age. [ABSTRACT FROM AUTHOR]

Patients with variants in CUL4B exhibit syndromic intellectual disability (MIM #300354). A seven-year-old boy presented with intellectual disability, a history of seizure, characteristic facial features, and short stature. Whole-exome sequencing detected a c.974+3A>G variant in CUL4B, which was subsequently confirmed to disrupt mRNA splicing. The current patient showed less pronounced phenotypic features compared with the previously reported cases. This report, therefore, provides evidence of genotype–phenotype correlations in CUL4B-related disorders. [ABSTRACT FROM AUTHOR]

A loss of function mutation in SLC9A6 (Xq26.3) is responsible for Christianson syndrome in males. We identified a novel splicing mutation (NM_006359.2:c.1141-8C>A) of SLC9A6 in a seven-year-old boy with microcephaly, severe developmental delay, and intractable epilepsy. Functional analysis found multiple aberrant transcripts, none of which maintained the canonical open reading frame. Computer prediction tools, however, failed to detect all of the aberrant transcripts. [ABSTRACT FROM AUTHOR]