Recent medical advances have significantly improved the life expectancy of individuals with congenital heart disease (CHD); however, these children remain at increased risk of co-occurring neurodevelopmental disorders (NDD), such as attention-deficit/hyperactivity disorder and autism spectrum disorder. Although prenatal environmental factors, including placental dysfunction and altered oxygen levels in utero, as well as postnatal events such as cardiac surgery, may contribute to this increased risk, shared genetic factors may also underlie both conditions. Therefore, this study is aimed at investigating genomic, transcriptomic and epigenomic findings in patients with NDD and/or CHD using an integrative multiomic approach. A cohort of 14 trios and one duo was recruited: Two probands had both NDD and CHD, two had CHD only and 11 had NDD only. Blood samples were analysed using whole-genome sequencing, RNA sequencing and DNA methylation profiling. We identified one large deletion (~2.5 Mb) and seven likely pathogenic/pathogenic (LP/P) variants, including two in autosomal dominant genes relevant to the patients' phenotypes and five in autosomal recessive genes consistent with carrier status. This included a likely pathogenic de novo splice-disrupting variant in the chromatin remodelling gene ARID1B, validated by RNA sequencing. DNA methylation analysis revealed epigenetic differences between CHD and NDD patients, with CHD patients showing elevated biological age acceleration. Comparison with a reference cohort of 178 controls identified four probands with extreme methylation dysregulation, including the individual with the ARID1B variant. Overall, these findings highlight the diagnostic and mechanistic value of integrative multiomic profiling in paediatric developmental disease cohorts.

This study aimed to develop and validate the Checklist for Chinese Toddlers with Autism, a culturally adapted early screening tool for autism spectrum disorder in children aged 12-24 months. The scale was developed by synthesizing early ASD symptom characteristics, reviewing international screening instruments, incorporating interviews with 15 medical professionals, and consulting eight experts in developmental behavioral pediatrics, child psychology, and psychometrics. The final scale comprises three dimensions (reciprocal social behaviors, social communication, interest behaviors and sensory perception) and 20 items assessed via behavioral observation. Initial validation involved 809 children (aged 12-24 months) to evaluate reliability and validity of the scale, and then determine a cutoff point to differentiate the severity levels of ASD. Further, the scale was applied in 4786 children from the neighborhood child health care clinics to test the screening value of the checklist. The results indicated that a cutoff score of 12 yielded optimal performance, with high sensitivity (0.95) and specificity (0.82). Community-based screening confirmed its efficacy in distinguishing between high likelihood and low likelihood children for ASD. Preliminary evidence indicates that the Checklist for Chinese Toddlers with Autism exhibits sound psychometric properties and may serve as an early screening tool for Chinese children with ASD aged 12-24 months, however, external validation is still required to establish its generalizability.

Neurodevelopmental disorders related to protein phosphatase 2 catalytic subunit alpha (PPP2CA) are currently recognized as Houge-Janssens syndrome 3 (OMIM: 618354), an autosomal dominant disorder characterized by developmental delay, intellectual disability, autism spectrum disorder, seizures, brain abnormalities, and hypotonia. Here, we report a patient with a PPP2CA variant. Trio-based whole-exome sequencing was performed on the patient and her parents, and a novel de novo heterozygous variant PPP2CA (NM_002715: c.218G > A, p.Gly73Asp) was identified, resulting in an amino acid substitution within the catalytic subunit. Clinically, the patient presented with epilepsy, hypotonia, attention-deficit/hyperactivity disorder, and intact intellectual functioning; there were no structural brain abnormalities. PPP2CA variants are rare, and the variant identified in this study has not been previously reported in the literature or public databases. Our findings support the pathogenicity of this variant and further expand the pathogenic variant spectrum of the PPP2CA gene. Furthermore, the observed genotype-phenotype correlation provides valuable information for prognosis and genetic counseling.

Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, are widely prescribed medications. Fluoxetine is considered a first-line pharmacological treatment for common psychiatric conditions such as anxiety, depression, and obsessive-compulsive disorder (OCD). In large clinical trials, fluoxetine has consistently demonstrated a strong safety and tolerability profile over the past 30 years. This case describes a 36-year-old Caucasian female with a history of autism spectrum disorder (ASD) and bipolar I disorder treated with lithium, who developed new-onset cognitive dysfunction following the up-titration of fluoxetine. Her fluoxetine dose was gradually titrated to 80 mg/day over several weeks, in accordance with dosing guidelines. At that dose, she began experiencing progressive memory loss and confusion, ultimately requiring hospitalization. Extensive evaluation ruled out other potential psychiatric or medical causes of cognitive decline. Upon discontinuation of fluoxetine and reduction of her longstanding lithium dose, her cognitive function improved after 2 weeks and returned to baseline within 4 weeks. While SSRIs are generally well-tolerated compared to other antidepressant classes, isolated reports suggest fluoxetine may be associated with reversible memory impairment in certain populations. This is the first documented case of reversible memory loss requiring hospitalization associated with fluoxetine in a middle-aged adult with complex comorbid psychiatric conditions-a demographic frequently prescribed this medication. When prescribing fluoxetine to patients with comorbid psychiatric conditions on lithium, clinicians may consider slow titration and proactive cognitive monitoring.

Catatonia requires in-person evaluation, but expansion of telehealth raises questions about virtual diagnosis and treatment. This case series examines outcomes of catatonia care delivered through telepsychiatry for patients with Intellectual Disability and other Neurodevelopmental Disorders. A retrospective chart review was conducted of patients seen through Ohio's Telepsychiatry Project (2009-present). Inclusion required diagnosis and treatment of catatonia via telehealth. Data collected included demographics, comorbidities, medications, and outcomes. Fourteen patients met inclusion criteria (ages 14-69; 87% male). All had Intellectual Disability; 60% also had autism spectrum disorder. Lorazepam was the primary treatment, titrated virtually, with clinical improvement in 71.4% of cases. Benefits included reduced aggression, self-injury, and regression, though a minority experienced worsening psychosis. Findings suggest telepsychiatry may be a feasible approach for diagnosis and management of catatonia in individuals with neurodevelopmental disorders. Structured assessment and ongoing monitoring remain essential. Future studies can address treatment response and outcomes of catatonia using telepsychiatry.

This study examines the quality of life, stress, and coping strategies of parents raising children with autism spectrum disorder in Kathmandu Valley. These parents face unique challenges, including caregiving demands, societal stigma, and limited support resources. Limited research exists on the psychosocial impacts these parents experience in Nepal, making this study crucial for understanding their struggles. This cross-sectional mixed-method study was conducted in autism care centers across Kathmandu Valley. Quantitative data from 140 parents was collected using validated scales (Autism Parenting Stress Index, Brief-COPE, Multidimensional Scale of Perceived Social Support, and Family Quality of Life Scale), analyzed with STATA/EZR, while qualitative data from semi-structured interviews was thematically analyzed using R package for Qualitative Data Analysis. Purposive sampling ensured diverse experiences, and the tools were pretested for reliability and validity. Parents' greatest stressors were concerns about their child's future independence (76.43%), acceptance (72.14%), communication (66.43%), and social development (51.44%). They primarily relied on active coping and planning, with family providing more consistent support than friends. Unemployed parents had a lower family quality of life than homemakers (p = 0.003). Greater use of emotion-focused (p = 0.017) and problem-focused coping (p < 0.001) was associated with lower family quality of life. Parents mostly faced stress over their child's future and communication. They commonly used coping strategies like acceptance, emotional support, and religion, though some resorted to negative methods like self-blame, substance use and hitting the child. Challenges like societal stigma, limited support, financial strain, and disrupted family relationships were common. Parental support networks and perceived support significantly influenced family quality of life. This study highlights that these parents face various psychosocial burdens and struggles that affect their quality of life and they need interventions to reduce stigma, improve family well-being to ultimately improve their ability to care for their children.