BACKGROUND: People with Intellectual Disabilities (PwID) are twenty times more likely than general population to have epilepsy. Guidance for prescribing antiseizure medication (ASM) to PwID is driven by trials excluding them. Levetiracetam (LEV) is a first-line ASM in the UK. Concerns exist regarding LEV\'s behavioural and psychological adverse effects, particularly in PwID. There is no high-quality evidence comparing effectiveness and adverse effects in PwID to those without, prescribed LEV.
METHODS: Pooled casenote data for patients prescribed LEV (2000-2020) at 18 UK NHS Trusts were analysed. Demographics, starting and maximum dose, adverse effects, dropouts and seizure frequency between ID (mild vs. moderate-profound (M/P)) and general population for a 12-month period were compared. Descriptive analysis, Mann-Whitney, Fisher\'s exact and logistic regression methods were employed.
RESULTS: 173 PwID (mild 53 M/P 120) were compared to 200 without ID. Mean start and maximum dose were similar across all groups. PwID (Mild & M/P) were less likely to withdraw from treatment (P = 0.036). No difference was found between ID and non-ID or between ID groups (Mild vs M/P) in LEV\'s efficacy i.e. >50 % seizure reduction. Significant association emerged between ID severity and psychiatric adverse effects (P = 0.035). More irritability (14.2 %) and aggression (10.8 %) were reported in M/P PwID.
CONCLUSIONS: PwID and epilepsy have high rates of premature mortality, comorbidities, treatment resistance and polypharmacy but remain poorly researched for ASM use. This is the largest studied cohort of PwID trialled on LEV compared to general population controls. Findings support prescribing of LEV for PwID as a first-line ASM.

This study compares two parent reports, the Mental Synthesis Evaluation Checklist (MSEC) and the Autism Treatment Evaluation Checklist (ATEC), with the Childhood Autism Rating Scale (CARS). The ATEC consists of four subscales, as follows: (1) expressive language, (2) sociability, (3) sensory awareness, and (4) health. The MSEC is complementary to the ATEC in measuring complex language comprehension. The parents of 143 autistic children, from 2 to 22 years of age (mean 6.7 ± 5.1 years), completed the MSEC and the ATEC questionnaires and a clinician assessed their CARS score. The CARS score correlated strongly with all parent reports, the complex language comprehension MSEC (r = 0.60, p < 0.0001), expressive language (r = 0.66, p < 0.0001), sociability (r = 0.58, p < 0.0001), sensory awareness (r = 0.71, p < 0.0001), and health (r = 0.53, p < 0.0001), as well as the total ATEC score (r = 0.75, p < 0.0001). The strongest correlation was between the CARS score and the composite of all five parent-reported scores (total ATEC + MSEC, r = 0.77, p < 0.0001). These results suggest a high fidelity of the MSEC and ATEC parent reports and especially of their composite score, total ATEC + MSEC.

UNASSIGNED: The TRAK1 gene is mapped to chromosome 3p22.1 and encodes trafficking protein kinesin binding 1. The aim of this study was to investigate the genotype-phenotype of TRAK1-associated epilepsy.
UNASSIGNED: Trio-based whole-exome sequencing was performed on a cohort of 98 patients with epilepsy of unknown etiologies. Protein modeling and the VarCards database were used to predict the damaging effects of the variants. Detailed neurological phenotypes of all patients with epilepsy having TRAK1 variants were analyzed to assess the genotype-phenotype correlations.
UNASSIGNED: A novel TRAK1 compound heterozygous variant comprising variant c.835C > T, p.Arg279Cys and variant c.2560A > C, p.Lys854Gln was identified in one pediatric patient. Protein modeling and VarCards database analyses revealed that the variants were damaging. The patient received a diagnosis of early infantile epileptic spasms with a developmental disorder; he became seizure-free through valproate and adrenocorticotropic hormone treatment. Further results for six variants in 12 patients with epilepsy indicated that biallelic TRAK1 variants (including homozygous or compound heterozygous variants) were associated with epilepsy with developmental disorders. Among these patients, eight (67%) had epileptic spasms and seven (58%) were intractable to anti-seizure medicines. Moreover, eight patients experienced refractory status epilepticus, of which seven (88%) died in early life. To our knowledge, this is the first reported case of epilepsy caused by TRAK1 compound heterozygous variants.
UNASSIGNED: Biallelic TRAK1 variants can cause epilepsy and developmental disorders. In these patients, seizures progress to status epilepticus, suggesting a high risk for poor outcomes and the requirement of early treatment.

Studies evaluating the association between prenatal ultrasounds and autism spectrum disorder (ASD) have largely produced negative results. Concern remains due to the rising identification of children with ASD and ultrasound use.
To evaluate the association between prenatal ultrasound use and ASD.
We used data from the Study to Explore Early Development, a multisite case-control study of preschool-aged children with ASD implemented during 2007-2012. We recruited cases from children receiving developmental disability services and randomly selected population controls from birth records. ASD case status was based on in-person standardised assessments. We stratified analyses by pre-existing maternal medical conditions and pregnancy complications associated with increased ultrasound use (ultrasound indications) and used logistic regression to model case status by increasing ultrasound counts. For pregnancies with medical record data on ultrasound timing, we conducted supplementary tests to model associations by trimester of exposure.
Among 1524 singleton pregnancies, ultrasound indications were more common for ASD cases than controls; respectively, for each group, no indications were reported for 45.1% and 54.2% of pregnancies, while ≥2 indications were reported for 26.1% and 18.4% of pregnancies. The percentage of pregnancies with multiple ultrasounds varied by case status and the presence of ultrasound indications. However, stratified regression models showed no association between increasing ultrasound counts and case status, either for pregnancies without (aOR 1.01, 95% CI 0.92, 1.11) or with ultrasound indications (aOR 1.01, 95% CI 0.95, 1.08). Trimester-specific analyses using medical record data showed no association in any individual trimester.
We found no evidence that prenatal ultrasound use increases ASD risk. Study strengths included gold-standard assessments for ASD case classification, comparison of cases with controls, and a stratified sample to account for conditions associated both with increased prenatal ultrasound use and ASD.

PUF60-related developmental disorder (also referred to as Verheij syndrome), resulting from haploinsufficiency of PUF60, is associated with multiple congenital anomalies affecting a wide range of body systems. These anomalies include ophthalmic coloboma, and congenital anomalies of the heart, kidney, and musculoskeletal system. Behavioral and intellectual difficulties are also observed. While less common than other features associated with PUF60-related developmental disorder, for instance hearing impairment and short stature, identification of specific anomalies such as ophthalmic coloboma can aid with diagnostic identification given the limited spectrum of genes linked with this feature. We describe 10 patients with PUF60 gene variants, bringing the total number reported in the literature, to varying levels of details, to 56 patients. Patients were recruited both via locally based exome sequencing from international sites and from the DDD study in the United Kingdom. Eight of the variants reported were novel PUF60 variants. The addition of a further patient with a reported c449-457del variant to the existing literature highlights this as a recurrent variant. One variant was inherited from an affected parent. This is the first example in the literature of an inherited variant resulting in PUF60-related developmental disorder. Two patients (20%) were reported to have a renal anomaly consistent with 22% of cases in previously reported literature. Two patients received specialist endocrine treatment. More commonly observed were clinical features such as: cardiac anomalies (40%), ocular abnormalities (70%), intellectual disability (60%), and skeletal abnormalities (80%). Facial features did not demonstrate a recognizable gestalt. Of note, but remaining of unclear causality, we describe a single pediatric patient with pineoblastoma. We recommend that stature and pubertal progress should be monitored in PUF60-related developmental disorder with a low threshold for endocrine investigations as hormone therapy may be indicated. Our study reports an inherited case with PUF60-related developmental disorder which has important genetic counseling implications for families.

Although past studies have identified predictors related to child injuries with developmental disorders, national-level research in Asia is limited. The objective of this study was to explore the risk factors for child injuries with developmental disorders in Taiwan using a national-level integrated database for the period between 2004-2015 (The Maternal and Child Health Database, National Health Insurance Research Database, Census Registry, and Indigenous Household Registration). Children younger than 12 years old who had records of visiting the ER or being hospitalized due to injury or without injury were included in this study. A 1:1 nested case-control study (injury vs. noninjury) to examine the risk factors for child injury with developmental disorder was performed. A total of 2,167,930 children were enrolled. The risk factors were associated with repeated ER visits or hospitalization: being indigenous (adjusted odds ratio [AOR]: 1.51; CI: 1.45-1.57); having a developmental disorder (AOR: 1.74; CI: 1.70-1.78); and having parents with illicit drug use (AOR: 1.48; CI: 1.32-1.66), alcohol abuse (AOR: 1.21; CI: 1.07-1.37), or a history of mental illness (AOR: 1.43; CI: 1.41-1.46). Being indigenous, having developmental disorders, and having parents with history of illicit drug use, alcohol abuse, or mental illness were predictors related to injuries in children.

BACKGROUND: Developmental disorders associated with Becker muscular dystrophy (BMD), possibly resulting from a lack of dystrophin in the brain, have been reported, but their importance is not fully understood. We report a case of a BMD patient who had been socially withdrawn due to mental retardation and autism spectrum disorder and could not receive appropriate medical services, resulting in delayed detection of severe cardiomyopathy and embolic strokes which developed as complications of BMD.
METHODS: The case is a 41-year-old male. In elementary school, he was the slowest runner in his class and had poor grades. He started missing school due to bullying in junior high school and had been socially withdrawn for 24 years. He developed difficulty walking due to progressive muscle weakness in the extremities and lost ambulation at age 36. At age 41, he was referred to our hospital by public health support services to address his social withdrawal. Muscle biopsy led to the diagnosis of BMD. Psychological examination revealed mild mental retardation and autism spectrum disorder, which may have resulted in social isolation. He had severe cardiomyopathy and asymptomatic cerebral infarction due to heart failure.
CONCLUSIONS: In BMD patients, developmental disorders can potentially hinder access to appropriate medical treatment. BMD is an important differential diagnosis for physically disabled children with developmental disorders. Early intellectual and psychological interventions and evaluation of complications are important for improving patient prognosis and quality of life.

Background: Developmental delay among children under 5 years of age is a serious global public health problem and much research has been carried out to find potential causes. Pesticides - especially organophosphates - are suspected to be one of the main causes of the problem.  This study aimed to investigate the association between pesticide use by the mother during pregnancy and preschool children development using a case-control study. Methods: Data on prenatal and postnatal pesticide exposure of 442 children with suspected developmental delay, and 413 controls with normal development were included for analysis. The children were matched for gender, age, and residency. Data on pesticide exposure were collected via interview with the mother, and data on pregnancy outcomes abstracted from hospital records.   Results: Chlorpyrifos exposure significantly increased the risk of developmental delay with an odds ratio (OR) of 3.71 (95% CI 1.03-13.36) for ever use of the pesticide, and an OR of 5.92 (95% CI 1.01-34.68) for postnatal exposure (p <0.05). Some other pesticides also had a positive association with developmental delay but none were statistically significant (p <0.05). Those pesticides were insecticide, fungicide, herbicide, and molluscicide. Individual pesticides with a positive association were glyphosate, paraquat, butachlor, methyl parathion (pholidon), savin, methomyl, endosulfan, carbosulfan, methamidophos, monochrotofos, mancozeb, and bordeaumixture. Conclusions: This case-control study found that chlorpyrifos and some other pesticide exposure during pregnancy was positively associated with developmental delay in children aged under 5 years. Further research should be conducted to better understand this potential effect of pesticides on child neurodevelopment, and the public - especially those who plan to have families - should be informed.

Cornelia de Lange syndrome is a rare genetic condition with developmental disorder and malformation affecting multiple systems. To describe the clinical and laboratory details and outcome of the children diagnosed with Cornelia de Lange syndrome, we retrospectively studied six cases who presented to our hospital between the years 2013 and 2015. Almost all had developmental retardation, with recurrent respiratory tract infections, and feeding difficulties. Synophrys with long curly eyelashes with low anterior and posterior hairline was present in all the children. Cornelia de Lange syndrome is a multisystem developmental disorder requiring interdisciplinary management. Symptomatic treatment generally given as therapy is very difficult. Early diagnosis and prompt management of associated disorder are useful for effective outcome of the disease.

Dandy-Walker syndrome (DWS) is a congenital brain malformation that is characterized by partial or complete agenesis of the cerebellar vermis and cystic dilatation of the 4th ventricle that shifts ventrolaterally to displace the cerebellar hemispheres. This case is a 68-year-old male veteran with complaints of new-onset cognitive disorder who was found to have previously unsuspected DWS on head computed tomography. This is one of the first case studies to present complete neuropsychological test results in a veteran with DWS. Despite the level of abnormality on imaging, the veteran functioned well until onset of mild cognitive impairments in late adulthood.