Clozapine for persons with neurodevelopmental disorders: a systematic review and expert recommendations for clinical practice.

INTRODUCTION: We aimed to synthesize the information on the risks and benefits of clozapine prescription for resistant challenging behavior in persons with neurodevelopmental disorders. METHODS: Articles were identified with MEDLINE, Web of Sciences and PsycINFO search from inception through January 2024. The review was restricted to persons with intellectual disability (ID) and/or autism spectrum disorder (ASD) without comorbid psychotic or affective disorder. Data were synthesized narratively. RESULTS: We identified 24 articles (13 case reports, eight chart studies, two controlled studies, one pharmaco-epidemiological study) including 296 patients with ID (n = 222) or ASD (n = 74) (10% aged ≤18 years). After clozapine initiation, a decreased frequency of challenging behavior persisting over time was reported in most participants included in clinical studies, and a significant reduction in the number of admissions in the population-based two-year mirror-image study. Adverse drug reactions were those commonly observed with clozapine, i.e. constipation, sedation, weight gain. CONCLUSIONS: Since only four participants were included in the controlled studies, the benefits of clozapine in neurodevelopmental disorders are supported by a body of evidence exclusively drawn from observational studies. Further studies are required to clarify the indications of clozapine with respect to the unmet need induced by resistant challenging behavior. REGISTRATION: PROSPERO database registration number CRD42024522343.

Awareness and Knowledge of Congenital Cytomegalovirus (cCMV) Among Audiologists and Speech-Language Pathologists in Saudi Arabia: A Cross Sectional Survey.

Congenital cytomegalovirus (cCMV) is the most prevalent congenital infection in the world. It can result in various neurodevelopmental disorders, one of which is environmental hearing loss among children. This study aimed to assess the awareness and knowledge of cCMV among audiologists and speech-language pathologists (SLPs) in Saudi Arabia and to seek their perception of it. An online survey was conducted from May to June 2023, targeting participants through social media, and a descriptive and inferential analysis was performed. A total of 107 participants (31 audiologists and 76 SLPs) were enrolled in this study. Awareness about cCMV was significantly higher among audiologists (84%) compared to SLPs (49%) (p-value < 0.001). However, both groups exhibited poor cCMV knowledge, which was revealed by their low mean knowledge scores (6.8/14 for audiologists and 5.7/14 for SLPs). The difference between their mean scores was non-significant (p-value > 0.05). The majority of SLPs and audiologists agreed that it is crucial for them to learn more about cCMV to enrich their professional backgrounds. This study emphasized the necessity for cCMV education for audiologists and SLPs. Increased awareness and knowledge may allow them to be more mindful of cCMV symptoms and therefore provide enhanced service to their pediatric patients.

Risk of psychiatric neurodevelopmental disorders after meningitis in childhood: a nationwide, population-based cohort study.

BACKGROUND: Few studies have investigated the risk of psychiatric neurodevelopmental disorders (PNDD) after childhood meningitis. METHODS: Nationwide population-based cohort study (Denmark, 1995-2021) of children with positive cerebrospinal fluid for bacteria or enterovirus, stratified on age as young infants (0 to <90 days, n = 637) or older children (≥90 days to <17 years, n = 1,218). We constructed a comparison cohort from the general population (n = 18,550), and cohorts of siblings of participants. As risk estimates of PNDD we calculated age- and sex-adjusted hazard ratios (aHRs) with 95% confidence intervals (95%CI). RESULTS: Children with bacterial meningitis had increased risks of PNDD, especially learning and intellectual developmental disorders (young infants: aHR 4.2, 95%CI: 2.4-7.1; older children: aHR 1.5, 95%CI: 1.0-2.3), attention deficit disorder (ADHD) (young infants: aHR 2.8, 95%CI: 1.5-5.2; older children: 1.4, 95%CI: 0.9-2.2) and redemption of ADHD medication (young infants: aHR 2.2, 95%CI: 1.0-4.7; older children: 1.5, 95%CI: 1.0-2.3). Young infants with bacterial meningitis additionally had increased risks of autism spectrum disorders (aHR 1.9, 95%CI: 0.9-4.1) and behavioural and emotional disorders (aHR 2.0, 95%CI: 1.0-3.9). In young infants, the excess risk of PNDD was especially observed in premature children. Siblings of older children with bacterial meningitis also had increased risks of PNDD. Children with enteroviral meningitis at any age did not have increased risks of PNDD or redemption of ADHD medication. CONCLUSIONS: Bacterial meningitis in childhood is associated with subsequent diagnosis of PNDD, while enteroviral meningitis is not. The association appears to be partly explained by prematurity and familial and socioeconomic factors.

Helsmoortel-Van der Aa syndrome in a 13-year-old girl with autistic spectrum disorder, dysmorphism, a right solitary kidney, and polycystic ovaries: a case report.

BACKGROUND: Helsmoortel-Van der Aa syndrome was officially documented in 2014. Helsmoortel-Van der Aa syndrome is an extremely rare complex neurodegenerative disorder characterized by reduced intellectual capacity, motor dysfunction, facial dysmorphism, impaired development, and an increased predisposition to autism spectrum disorder. In addition, many patients also present with neuropsychiatric disorders, including attention deficit hyperactivity disorder, anxiety disorders, and various behavioral abnormalities. Helsmoortel-Van der Aa syndrome is challenging to identify solely on the basis of symptoms, and genetic investigations, including exome sequencing, may facilitate diagnosis. CASE PRESENTATION: We report a case of 13-year-old Saudi patient who presented with dysmorphic features as illustrated in Fig. 1, severe mental retardation, autism spectrum disorder, and attention deficit hyperactivity disorder. Initial genetic testing was unremarkable; thus, a clinical exome analysis was performed to identify the genetic basis of the condition. CONCLUSIONS: Clinical exome analysis indicated an autosomal dominant Helsmoortel-Van der Aa syndrome with a likely pathogenic de novo variant within the activity-dependent neuroprotector homeobox (ADNP) gene not previously reported in Helsmoortel-Van der Aa syndrome. The patient had a right-sided solitary kidney and polycystic ovaries, conditions that were not previously associated with HVDAS.

Temperature dependent cholinergic synapse induced by triphenyl phosphate and tris(1.3-dichloroisopropyl) phosphate via thyroid hormone synthesis in Cyprinus carpio.

Triphenyl phosphate (TPHP) and tris(1.3-dichloroisopropyl) phosphate (TDCIPP) are emerging contaminants that pervade diverse ecosystems and impair the thyroid and neural signaling pathways. The intricate interactions between thyroid and neurodevelopmental effects mediated by TPHP and TDCIPP remain elusive. This study integrates in vivo, in vitro, and in silico approaches to elucidate these mechanisms in Cyprinus carpio at varying temperatures. It showed that TPHP and TDCIPP hindered fish growth, particularly at low temperatures, by interfering with thyroid hormone synthesis and transport processes. Both compounds have been identified as environmental hormones that mimic thyroid hormone activity and potentially inhibit acetylcholinesterase, leading to neurodevelopmental disorders characterized by brain tissue damage and disrupted cholinergic synapses, such as axon guidance and regeneration. Notably, the bioaccumulation of TPHP was 881.54 % higher than that of TDCIPP, exhibiting temperature-dependent variations with higher levels of TDCIPP at low temperatures (20.50 % and 250.84 % above optimum and high temperatures, respectively), suggesting that temperature could exacerbate the toxicity effects of OPEs. This study sheds new light on the mechanisms underlying thyroid endocrine disruption and neurodevelopmental toxicity in C. carpio. More importantly, these findings indicate that temperature affects the environmental fate and effects of TPHP and TDCIPP, which could provide an important basis for ecological environmental zoning control of emerging contaminants in the future.

Familial coaggregation of major psychiatric disorders and neurodevelopmental disorders among first-degree relatives of individuals with generalized anxiety disorder.

BACKGROUND: Anxiety disorders, major psychiatric disorders (e.g., schizophrenia and major affective disorders), and neurodevelopmental disorders (e.g., autism and attention-deficit/hyperactivity disorder [ADHD]) may cluster together within families. However, whether the first-degree relatives (FDRs) of individuals with generalized anxiety disorder (GAD) are at an elevated risk of neurodevelopmental or major psychiatric disorders remains unknown. METHODS: We identified 2,378,190 FDRs of patients with GAD and 9,512,760 birth year-matched and sex-matched controls from Taiwan's National Health Insurance Research Database. Neurodevelopmental disorders, including autism and ADHD, and major psychiatric disorders, including schizophrenia, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, and GAD, were identified. RESULTS: The FDRs-parents, offspring, and siblings-of individuals with GAD were more likely to be diagnosed as having schizophrenia (relative risk: 1.22), bipolar disorder (1.36), major depressive disorder (1.29), autism (1.20), ADHD (1.52), obsessive-compulsive disorder (1.21), and GAD (1.61) than are the FDRs of individuals without GAD. CONCLUSION: Our findings support the notion of a familial coaggregation between GAD, major psychiatric disorders, and neurodevelopmental disorders. Future studies should elucidate the definitive genetic etiology of this familial coaggregation.

Case report: A novel TLK2 variant with a neuropsychiatric phenotype from a Chinese family.

Background: Tousled-like kinase 2 (TLK2) gene variant-related neurodevelopmental disorder was recently described. The haploinsufficiency of TLK2 was considered the most likely underlying disease mechanism, leading to a consistent neurodevelopmental phenotype. So far, only four studies, conducted on 49 patients from North America and Europe, have been reported. Case presentation: In this study, we reported a Chinese family with a TLK2-related neuropsychiatric phenotype. The proband, a boy aged 2 years and 6 months, presented with temper tantrums, mood lability, aggressiveness, congenital astigmatism, and distinctive facial dysmorphism. Whole-exome sequencing identified a novel heterozygous variation in TLK2 gene (c.49dupG, p. E17Gfs*10) in them. His father carried the same TLK2 gene variant and exhibited anxiety and irritability. The parental grandparents and other family members had no such variation. Moreover, the proband was found to have global developmental delay, autism-like symptoms, and mild elevated homo-vanillic acid (HVA) and 2,3-dihydroxy-2-methylbutyric acid levels tested in urine. Conclusion: Herein, we identified a novel TLK2 variant from a Chinese family and reported a new neuropsychiatric phenotype. This study also expanded the genotype profile of the newly defined TLK2-related neurodevelopmental disorder.

Role of vesicular monoamine transporter-2 for treating attention deficit hyperactivity disorder: a review.

RATIONALE: The Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) classifies attention deficit hyperactivity disorder (ADHD) as a neurodevelopmental disorder that interferes with human functioning and development. As the clinical presentation of ADHD involves a deficiency in executive function, neurocognitive deficits involving distinctive neuropathological changes must be present for clinical diagnosis. OBJECTIVES: The vesicular monoamine transporter (VMAT), specifically VMAT-2, plays a role in ADHD pathogenesis. In addition, experimental data show that the stimulants (amphetamines and methylphenidate) are first-line treatments for the condition because of their extensive interaction with VMAT-2. The interactions of peptides, bupropion, and nutritional supplements with VMAT-2 receptors have been researched, but more evidence is needed to elucidate their pharmacodynamic properties. Therefore, this literature review evaluated the current pharmacological treatment modalities, peptides, and nutritional supplements for ADHD that target the VMAT-2 system. METHODS, RESULTS, AND CONCLUSIONS: We obtained relevant studies from several platforms, including the National Center for Biotechnology, Clinical Key, Access Medicine, and PubMed. From the results of these studies, we observed that stimulants interact highly with the VMAT-2 transporter, with omega-3 fatty acids, peptides, and bupropion exerting some modulatory activity on VMAT-2. These agents should be considered for the future treatment of ADHD, although clinical-level research involving human participants is necessary.

Severe Neurodevelopmental Phenotype, Diagnostic and Treatment Challenges in Patients with SECISBP2 Deficiency.

PURPOSE: Defects in the gene encoding selenocysteine insertion sequence binding protein 2, SECISBP2, result in global impaired selenoprotein synthesis manifesting a complex syndrome with characteristic serum thyroid function tests due to impaired thyroid hormone metabolism. Knowledge about this multisystemic defect remains limited. METHODS: Genetic and laboratory investigations were performed in affected members from six families presenting with short stature, failure to thrive. RESULTS: Four probands presented a complex neurodevelopmental profile, including absent speech, autistic features, and seizures. Pediatric neurological evaluation prompted genetic investigations leading to the identification of SECISBP2 variants before knowing the characteristic thyroid tests in two cases. Thyroid hormone treatment improved motor development, while speech and intellectual impairments persisted. This defect poses great diagnostic and treatment challenges for clinicians, as illustrated by a case that escaped detection for 20years, as SECISBP2 was not included in the neurodevelopmental genetic panel, and his complex thyroid status prompted anti-thyroid treatment instead. CONCLUSION: This syndrome uncovers the role of selenoproteins in humans. The severe neurodevelopmental disabilities manifested in four patients with SECISBP2 deficiency highlight an additional phenotype in this multisystem disorder. Early diagnosis and treatment are required, and long-term evaluation will determine the full spectrum of manifestations and the impact of therapy.

Elucidating the clinical and genetic spectrum of inositol polyphosphate phosphatase INPP4A-related neurodevelopmental disorder.

PURPOSE: Biallelic INPP4A variants have recently been associated with severe neurodevelopmental disease in single case reports. Here, we expand and elucidate the clinical-genetic spectrum and provide a pathomechanistic explanation for genotype-phenotype correlations. METHODS: Clinical and genomic investigations of 30 individuals were undertaken alongside molecular and in silico modelling and translation reinitiation studies. RESULTS: We characterize a clinically variable disorder with cardinal features including global developmental delay, severe-profound intellectual disability, microcephaly, limb weakness, cerebellar signs and short stature. A more severe presentation associated with biallelic INPP4A variants downstream of exon 4 has additional features of (ponto)cerebellar hypoplasia, reduced cerebral volume, peripheral spasticity, contractures, intractable seizures and cortical visual impairment. Our studies identify the likely pathomechanism of this genotype-phenotype correlation entailing translational reinitiation in exon 4 resulting in an N-terminal truncated INPP4A protein retaining partial functionality, associated with less severe disease. We also identified identical reinitiation site conservation in Inpp4a-/- mouse models displaying similar genotype-phenotype correlation. Additionally, we show fibroblasts from a single affected individual exhibit disrupted endocytic trafficking pathways, indicating the potential biological basis of the condition. CONCLUSION: Our studies comprehensively characterise INPP4A-related neurodevelopmental disorder and suggest genotype-specific clinical assessment guidelines. We propose the potential mechanistic basis of observed genotype-phenotype correlations entails exon 4 translation reinitiation.

Immune system dysfunction and inflammation in aging Shank3b mutant mice, a model of autism spectrum disorder.

Introduction: Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental Q8 conditions characterized by deficits in social interaction/communication and restrictive/repetitive behaviors. Recent studies highlight the role of immune system dysfunction and inflammation in ASD pathophysiology. Indeed, elevated levels of pro-inflammatory cytokines were described in the brain and peripheral blood of ASD individuals. Despite this, how this pro-inflammatory profile evolves with aging and whether it may be associated with behavioral deficits is unknown. In this work, we explored the impact of aging on motor behavior and inflammation using Shank3b mutant mice, a model for syndromic ASD. Methods: Using RT-qPCR and flow cytometry, we examined the expression of key pro-inflammatory molecules in the cerebellum, bone marrow, spleen, and peripheral blood, comparing adult and old Shank3b +/+, Shank3b +/-, and Shank3b -/- mice. Results and discussion: Our findings revealed genotype- and age-related differences in inflammation and motor behavior, with Shank3b-/- mice exhibiting accelerated aging and motor impairments. Correlations between pro-inflammatory molecules and behavioral deficits suggest that a link may be present between systemic inflammation and ASD-related behaviors, underscoring the potential role of age-related inflammation ("inflammaging") in exacerbating ASD symptoms.

Key roles of C2/GAP domains in SYNGAP1-related pathophysiology.

Mutations in SYNGAP1 are a common genetic cause of intellectual disability (ID) and a risk factor for autism. SYNGAP1 encodes a synaptic GTPase-activating protein (GAP) that has both signaling and scaffolding roles. Most pathogenic variants of SYNGAP1 are predicted to result in haploinsufficiency. However, some affected individuals carry missense mutations in its calcium/lipid binding (C2) and GAP domains, suggesting that many clinical features result from loss of functions carried out by these domains. To test this hypothesis, we targeted the exons encoding the C2 and GAP domains of SYNGAP. Rats heterozygous for this deletion exhibit reduced exploration and fear extinction, altered social investigation, and spontaneous seizures-key phenotypes shared with Syngap heterozygous null rats. Together, these findings indicate that the reduction of SYNGAP C2/GAP domain function is a main feature of SYNGAP haploinsufficiency. This rat model provides an important system for the study of ID, autism, and epilepsy.

Deoxyhypusine synthase deficiency syndrome zebrafish model: aberrant morphology, epileptiform activity, and reduced arborization of inhibitory interneurons.

DHPS deficiency syndrome is an ultra-rare neurodevelopmental disorder (NDD) which results from biallelic mutations in the gene encoding the enzyme deoxyhypusine synthase (DHPS). DHPS is essential to synthesize hypusine, a rare amino acid formed by post-translational modification of a conserved lysine in eukaryotic initiation factor 5 A (eIF5A). DHPS deficiency syndrome causes epilepsy, cognitive and motor impairments, and mild facial dysmorphology. In mice, a brain-specific genetic deletion of Dhps at birth impairs eIF5AHYP-dependent mRNA translation. This alters expression of proteins required for neuronal development and function, and phenotypically models features of human DHPS deficiency. We studied the role of DHPS in early brain development using a zebrafish loss-of-function model generated by knockdown of dhps expression with an antisense morpholino oligomer (MO) targeting the exon 2/intron 2 (E2I2) splice site of the dhps pre-mRNA. dhps knockdown embryos exhibited dose-dependent developmental delay and dysmorphology, including microcephaly, axis truncation, and body curvature. In dhps knockdown larvae, electrophysiological analysis showed increased epileptiform activity, and confocal microscopy analysis revealed reduced arborisation of GABAergic neurons. Our findings confirm that hypusination of eIF5A by DHPS is needed for early brain development, and zebrafish with an antisense knockdown of dhps model features of DHPS deficiency syndrome.

Novel KIF26A variants associated with pediatric intestinal pseudo-obstruction (PIPO) and brain developmental defects.

Pediatric intestinal pseudo-obstruction (PIPO) is a rare congenital disorder of the enteric nervous system with distal colon aganglionosis potentially leading to intestinal obstruction. Recently, biallelic variants in KIF26A, encoding a crucial motor protein for the migration and differentiation of enteric neural crest cells, have been associated with a neurodevelopmental condition featuring cortical defects and PIPO-like features, though in absence of aganglionosis. So far, only 10 patients have been reported. In this study, we investigated three subjects with congenital hydrocephalus, neurodevelopmental impairment, and intestinal obstruction megacolon syndrome. Brain MRI revealed malformations within cortical dysplasia spectrum, including polymicrogyria and heterotopia. Pathology study of the intestine revealed aganglionosis and elevated acetylcholinesterase activity in parasympathetic nerve fibers. Through trio-exome sequencing (ES), we detected four novel biallelic KIF26A variants, including two missense changes (#1) and two distinct homozygous truncating variants in (#2 and #3). All variants are rare and predicted to be deleterious according to in silico tools. To characterize the impact of the missense variants, we performed 3D protein modeling using Alphafold3 and YASARA. Mutants exhibited increased energy scores compared to wild-type protein, supporting a significant structural destabilization of the protein. Our study expands the genotype and phenotype spectrum of the emerging KIF26A-related disorder.

Biallelic EPB41L3 variants underlie a developmental disorder with seizures and myelination defects.

Erythrocyte Membrane Protein Band 4.1 Like 3 (EPB41L3: NM_012307.5), also known as DAL-1, encodes the ubiquitously expressed, neuronally enriched 4.1B protein, part of the 4.1 superfamily of membrane-cytoskeleton adaptors. 4.1B plays key roles in cell spreading, migration, and cytoskeletal scaffolding that support oligodendrocyte axon adhesions essential for proper myelination. We herein describe six individuals from five unrelated families with global developmental delay, intellectual disability, seizures, hypotonia, neuroregression, and delayed myelination. Exome sequencing identified biallelic variants in EPB41L3 in all affected individuals: two nonsense (c.466C>T, p.(R156*); c.2776C>T, p.(R926*)) and three frameshift (c.666delT, p.(F222Lfs*46); c.2289dupC, p.(V764Rfs*19); c.948_949delTG, p.(A317Kfs*33)). Quantitative-real time PCR and Western blot analysis in human fibroblasts harbouring EPB41L3:c.666delT, p.(F222Lfs*46) indicate ablation of EPB41L3 mRNA and 4.1B protein expression. Inhibition of the nonsense mediated decay (NMD) pathway led to an upregulation of EPB41L3:c.666delT transcripts, supporting NMD as a pathogenic mechanism. Epb41l3-deficient mouse oligodendroglia cells showed significant reduction in mRNA expression of key myelin genes, reduced branching, and increased apoptosis. Our report provides the first clinical description of an autosomal recessive disorder associated with variants in EPB41L3, which we refer to as EPB41L3-associated developmental disorder (EADD). Moreover, our functional studies substantiate the pathogenicity of EPB41L3 hypothesized loss-of-function variants.

Efficacy and Safety of Alpha-2 Agonists in Autism Spectrum Disorder: A Systematic Review.

BACKGROUND: This analysis is a systematic literature review assessing efficacy and adverse effects of three alpha-2 agonists for the symptomatic management of autism spectrum disorder (ASD). METHODS: The present investigation involved an extensive systematic search for eligible studies in PubMed, Embase, Cochrane Library, and Google Scholar. Nine studies, collectively incorporating 226 patients, were assessed. RESULTS: The results demonstrated promising indications for use of alpha-2 agonists in the symptomatic management of autism spectrum disorders, including improvement of hyperactivity, impulsivity, attention deficit symptoms, irritability, and stereotypies in many of the participants studied. CONCLUSION: The present investigation encourages physicians to consider treatment outcomes of clonidine, guanfacine, and lofexidine to determine the most effective management of ASD-related symptoms and to minimize adverse effects. However, our review cannot provide definitive treatment protocols related to various study limitations.

Misdiagnosis in an Autistic Adolescent.

With the increase in autism diagnoses in recent years due to improved public and clinical awareness, the association between autism and mental health has emerged as an important issue for patients and their caregivers. Although many with autism spectrum disorder also have coexisting mental health conditions, there exist differences in the presentation and etiology of these symptoms. This case report explains an interaction with a 17-year-old adolescent autistic male with a history of mild depression who was found non-responsive in the shower at home. Although the emergency medical team interpreted the scene as an attempted suicide, after lengthy interviews with the patient and the patient's family, the psychiatry team revealed a pre-existing condition, subdural empyema, that caused him seizures. This case highlights how autism characteristics can mask other relevant clinical details and delay proper diagnosis and treatment, especially when patients are non-responsive or exhibiting atypical behavior. It also underscores the importance of investigating all relevant clinical diagnoses, including those not related to psychiatric conditions. It is vital that healthcare providers learn how to effectively communicate with autistic patients to ensure proper treatment and improve patient outcomes.

Dissecting CASK: Novel splice site variant associated with male MICPCH phenotype.

CASK (MIM#300172), encoding a calcium/calmodulin-dependent serine protein kinase, is crucial for synaptic transmission and gene regulation during neural development. Pathogenic variants of CASK are known to cause several neurodevelopmental disorders, including X-linked intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH). This study introduces a novel, de novo synonymous CASK variant (NM_001367721.1: c.1737G>A, p.(Glu579=)), discovered in a male patient diagnosed with MICPCH, characterized by microcephaly, developmental delay, visual impairment, and myoclonic seizures. The variant disrupts a donor splice-site at the end of exon 18. Transcriptomic analysis of blood identified 12 different CASK transcripts secondary to the synonymous variant. Nearly one third of these transcripts were predicted to result in nonsense mediated decay or protein degradation. Protein modeling revealed structural alterations in the PDZ functional domain of CASK, due to exon 18 deletion. Our findings highlight the utility of transcriptomic analysis in demonstrating the underlying disease mechanism in neurodevelopmental disorders.

Regional Disparities in Growth Patterns of Children with Cerebral Palsy: A Comparative Analysis of Saudi Arabian, UK, and US Data.

AIM: In order to understand the global variations in the growth trajectories of cerebral palsy patients, this study aimed to compare the growth patterns of cerebral palsy patients in Saudi Arabi with United States and United Kingdom counterparts. METHOD: Anthropometric data from 107 participants with cerebral palsy in Saudi Arabia were collected, including age, gender, cerebral palsy type, Gross Motor Function Classification System level, birth weight, weight at assessment, height at assessment, body mass index, and head circumference at assessment. RESULTS: This study found discrepancies between the growth patterns of Saudi Arabian children with cerebral palsy and United Kingdom and the United States growth charts, particularly among those with severe cerebral palsy. Significant differences were observed in weight, height, and body mass index z-scores when comparing Saudi Arabian data with the United kingdom and United States reference data. INTERPRETATION: These findings emphasize the importance of validating growth charts across different populations to ensure accurate monitoring and clinical management of children with cerebral palsy. Additionally, this study highlights the need for region-specific growth references to better address the diverse needs of individuals with cerebral palsy worldwide.

Association between Motor Skills, Occupational Performance, and Mental Health in Japanese Children with Neurodevelopmental Disorders: A Cross-Sectional Correlational Study.

BACKGROUND: Motor skills have been linked to executive functions (EFs) in children with developmental coordination disorder (DCD). However, the traits of other neurodevelopmental disorders (NDDs), such as attention-deficit/hyperactivity disorder and autism spectrum disorder, remain overlooked. Therefore, this study explored the association between motor skills, occupational performance, and mental health in older kindergarten children with DCD and other NDDs. Overall, 95 participants aged 5-6 years were included in this study and divided into four groups: DCD traits (DCD-t), DCD-t + NDD traits (DCD-t + NDD-t), NDD-t-only, and typically developing children. Motor skills, EFs, and mental health were assessed using the DCD Questionnaire (DCDQ-J) and Movement Assessment Battery for Children-Second Edition, School Assessment of Motor and Process Skills (S-AMPS), and the Strengths and Difficulties Questionnaire (SDQ), respectively. The DCD-t + NDD-t group exhibited a strong correlation between the S-AMPS motor skill score and the DCDQ-J fine motor skill score (r = 0.88, p < 0.001) and between the total DCDQ-J score and the SDQ Total Difficulties Score (r = -0.94, p < 0.001). The findings indicate that children with DCD-t and NDD-t are more likely to experience EF and mental health problems than those with DCD-t only.