OBJECTIVE: PCDH19 gene variants, termed PCDH19 clustering epilepsy, represent a distinct etiology of epilepsy. This study aimed to elucidate the clinical manifestations and explore the genotypes and phenotypes of children affected by PCDH19 clustering epilepsy.
METHODS: This retrospective study included medical history, magnetic resonance imaging, video-electroencephalography, and genetic analysis of patients diagnosed with PCDH19 Clustering Epilepsy at the Neurology Department of Beijing Children\'s Hospital from 2015 to 2023. Chi-square tests and logistic regression analyses were conducted to study the factors associated with developmental delay in patients.
RESULTS: The age at seizure onset ranged from 5 to 61 months among all 30 patients (median 14 months; IQR 9.25-22.5 months). Among the 30 patients, 29 were female and 1 was male. Clusters of seizures and fever-triggered seizures were observed, with the most prevalent seizure types being focal to bilateral tonic-clonic seizures (FBTCS). Seizures were successfully controlled in 15 patients. Unfortunately, one patient experienced a sudden unexpected death in epilepsy (SUDEP). Additionally, 14 patients had hereditary mutations, 14 had de novo mutations, 1 had both hereditary and de novo mutations, and 1 male patient had a mosaic component mutation of 0.64 due to a somatic mutation. Developmental delays were identified in 17 patients (56.7 %), and 6 patients (20 %) were diagnosed with autism spectrum disorder (ASD). Among the 17 patients, 9 experienced developmental delays before the onset of epilepsy, while 8 were initially normal but later developed developmental delays during disease progression. Statistical analysis revealed that the presence of drug-resistant epilepsy was an independent risk factor for the occurrence of developmental delays (P = 0.020, OR = 9.758, 95 % CI (1.440-66.111)).
CONCLUSIONS: In this study, 13 new potential rare pathogenic variations in PCDH19 clustering epilepsy were identified. The clinical features observed in patients are consistent with known phenotypic features, and we found that patients with drug-resistant epilepsy are more likely to have developmental delays. The severity of the phenotype in patients with PCDH19 variants ranged from drug-responsive seizures to refractory epilepsy.

OBJECTIVE: PAFAH1B1, also known as LIS1, is associated with type I lissencephaly in humans, which is a severe developmental brain disorder believed to result from abnormal neuronal migration. Our objective was to characterize the genotypes and phenotypes of PAFAH1B1-related epilepsy.
METHODS: We conducted a comprehensive analysis of the medical histories, magnetic resonance imaging findings, and video-electroencephalogram recordings of 11 patients with PAFAH1B1 variants at the Neurology Department of Beijing Children\'s Hospital from June 2017 to November 2022.
RESULTS: The age of onset of epilepsy ranged from 2 months to 4 years, with a median onset age of 5 months. Among these 11 patients (comprising 6 boys and 5 girls), all were diagnosed with lissencephaly type 1. Predominantly, generalized tonic-clonic and spasm seizures characterized PAFAH1B1-related epilepsy. Additionally, 10 out of the 11 patients exhibited severe developmental disorders. All patients exhibited de novo variants, with three individuals displaying 17p13.3 deletions linked to haploinsufficiency of PAFAH1B1. Four variants were previously unreported. Notably, three patients with 17p13.3 deletions displayed developmental delay and drug resistant epilepsy, whereas the single patient with mild developmental delay, Intelligence Quotient (IQ) 57 and well-controlled seizures had a splicing-site variant.
CONCLUSIONS: The severity of the phenotype in patients with PAFAH1B1 variants ranged from drug-responsive seizures to severe epileptic encephalopathy. These observations underscore the clinical heterogeneity of PAFAH1B1-related disorders, with most patients exhibiting developmental disorders. Moreover, the severity of epilepsy appears to be linked to genetic variations.

UNASSIGNED: CHD2 is a member of the chromodomain helicase DNA-binding (CHD) family of proteins, which have important roles in the regulation of gene expression. Dysregulation of this protein may lead to various disorders.
UNASSIGNED: To delineate the genotypes and phenotypes of CHD2-related epilepsy.
UNASSIGNED: We analyzed the medical history, magnetic resonance imaging findings, and video-electroencephalogram recordings of 17 patients with CHD2 mutations in the Neurology Department of Beijing Children\'s Hospital from June 2016 to June 2021.
UNASSIGNED: Age at seizure onset ranged from 6 months to 10 years; the median age at onset was 4 years. Generalized tonic-clonic, myoclonic, eyelid myoclonic, atonic, atypical absence, myoclonic-atonic, and spasm seizures were observed. Ten of the 17 patients had multiple types of seizures. One patient exhibited photosensitivity epilepsy and one patient exhibited grid image-induced visual reflex epilepsy. Developmental disability was present in 14 patients, while autism features were present in five patients. Sixteen patients had de novo mutations of CHD2; one patient had an inherited variant. Eleven mutations were novel. One patient had two mutations; that patient exhibited development delay and refractory epilepsy. Seizures were controlled in eight patients, improved in seven patients, and resistant to treatment in two patients.
UNASSIGNED: Phenotype severity in patients with CHD2 variants ranged from drug-responsive seizures to severe epileptic encephalopathy. Most patients exhibited developmental disorders.

In the recent 3 years, subjects with Pumilio1-associated developmental disability, ataxia, and seizure syndrome have been identified as harboring Pumilio homolog 1 (PUM1) mutations. However, the characteristics of the seizure phenotype remain to be elucidated. We herein described a 3-year-old female proband who was diagnosed with developmental and epileptic encephalopathy presenting with some features suggestive of a Dravet-like syndrome. For genetic analyses, trio-based whole-exome sequencing and array comparative genomic hybridization were performed. Consequently, a de novo heterozygous missense variant was identified in exon 22 of the PUM1 gene: NM_001020658: c.3439C > T (p.Arg1147Trp). Upon thoroughly reviewing the existing literature, nine cases of PUM1 mutation-related epilepsy were identified, and their clinical features were summarized. A relationship between PUM1 mutation and clinical manifestations characteristic of a Dravet-like syndrome was proposed. To our knowledge, this is the first report of a patient with PUM1 mutation presenting with a Dravet-like syndrome.

Participation in community activities contributes to child development and health-related quality of life (HRQOL), but restricted participation has been reported in children with disabilities. Occupational performance coaching (OPC) is an intervention that targets participatory goals in child performance through coaching parents, with evidence of effectiveness for pediatric populations. Little is known about the feasibility of OPC in Hong Kong, or its effect on children\'s community participation and HRQOL. A mixed-methods case study design was applied to explore Hong Kong parents\' experience of OPC in relation to goal achievement, community participation, and HRQOL change in children. Four parents of young children with developmental disabilities (aged five to six years) received OPC for three to eight sessions within one to three months. Quantitative pre- and post-intervention data were analyzed descriptively. Semi-structured interviews with parents were conducted at post-intervention, and analyzed using content analysis. Results showed a trend of improvement in goal performance, child involvement in community activities, and specific aspects of HRQOL among most participants. Parents perceived undertaking OPC positively, described gaining insights and skills, and felt supported. The findings suggest that OPC warrants further investigation for use in Hong Kong, to promote children\'s community participation and quality of life.

The purpose of this study was to investigate the effects of Tai Chi (TC) on anthropometric parameters and physical fitness among children and adolescents with intellectual disabilities (ID).
Sixty-six Chinese individuals engaged in sport-related extracurricular activities (TC and aerobic exercise (AE)) as exercise interventions or arts/crafts activities as a control condition (CON). The experimental protocol consisted of a baseline assessment, a 12-week intervention period, and a post-intervention assessment.
Significant interaction effect was only observed in the performance of a 6-min walk test. After 12 weeks of intervention, the AE group had significant changes in body mass index (p = 0.006, d = 0.11), sit-ups (p = 0.030 and d = 0.57), and 6-min walk test (p = 0.005, d = 0.89). Significant increases in vertical jump (p = 0.048, d = 0.41), lower-limb coordination (p = 0.008, d = 0.53), and upper-limb coordination (p = 0.048, d = 0.36) were observed in the TC group. Furthermore, the TC group demonstrated significantly greater improvements on balance compared to the control group (p = 0.011).
TC may improve leg power and coordination of both lower and upper limbs, while AE may be beneficial for body mass index, sit-ups and cardiorespiratory fitness.

The purpose of this study was to investigate the prevalence of and contributing factors to osteopenia and osteoporosis among people with intellectual disabilities (ID) or/and developmental disabilities (DD) residing in a disability institution in Taiwan. The present study was conducted at one disability institution in Taiwan and recruited 184 institutionalized residents with ID and/or DD (115 men and 69 women aged 18-72 years) for analysis. For all residents with ID and/or DD, information was obtained about their age, gender, level of ID, BMI, and bone mineral density (BMD). BMD is a measurement of calcium levels in bones that can estimate the risk of osteoporosis and bone fractures. Bone tests were divided into three outcome categories based on their calcaneal BMD T-scores: Normal BMD, a T-score≧-1; Osteopenia, -2.5≦T-score<-1; and Osteoporosis, a T-score<-2.5. The results revealed that 46.2% of cases were normal and that 27.7% and 26.1% of cases had osteopenia and osteoporosis, respectively. Multiple logistic regression analyses found that male gender (OR=2.482, 95% CI=1.04-5.93, p<0.05), age≧40 years (OR=3.051, 95% CI=1.07-8.69, p<0.05) and being overweight/obese (OR=0.395, 95% CI=0.17-0.93, p<0.05) were more likely to be associated with osteoporosis. Another model indicated that males (OR=2.169, 95% CI=1.12-4.19, p<0.05) and those aged≧40 years (OR=3.026, 95% CI=1.32-7, p<0.01) tended to have an increased risk for osteopenia and osteoporosis. To improve the bone quality of individuals with ID or/and DD and to decrease the occurrence of osteopenia and osteoporosis, this study highlights that we should pay much attention to the potential risk factors for bone quality in these vulnerable populations.