Neurodevelopmental Abnormalities Research Articles

Sex-specific associations between maternal thyroid peroxidase antibodies and cognitive development in preschool children: A prospective cohort study.

An association between maternal thyroid dysfunction throughout pregnancy and subsequent risk of neurodevelopmental abnormalities in offspring has been demonstrated. However, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism remain unclear. Therefore, in this study, we explored the association between maternal thyroid peroxidase antibody (TPOAb) positivity and cognitive development in preschool children. A total of 1849 mother-child pairs were recruited from the Ma'anshan Birth Cohort Study. During the follow-up period, an electrochemiluminescence immunoassay was used to retrospectively measure serum TPOAb levels in pregnant women. The cognitive development of preschool children was evaluated by using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition. A growth mixture model was used to fit the trajectory of TPOAb. Multiple linear regression and logistic regression models were used to explore the associations between the developmental trajectory of TPOAb-positivity at different gestational periods and the cognitive development of preschool children by sex. A total of 1849 mother-child pairs (mean [SD] age: 26.7 [3.6] years) were enrolled in the final study. Maternal TPOAb positivity in the first trimester was associated with a risk of below-average processing speed index in girls (OR: 2.07; 95% CI 1.06-4.01) and below-average full-scale intelligence quotient (FSIQ) in boys (OR: 2.36; 95% CI: 1.10-5.05). Maternal TPOAb positivity in the third trimester was associated with below-average working memory (WMI) (OR: 2.51; 95% CI: 1.02-6.20) in girls. In girls, the WMI (β = -3.17, 95% CI: -5.82--0.52), fluid reasoning index (FRI) (β = -4.49, 95% CI: -7.18--1.80), and FSIQ score (β = -2.43, 95% CI: -4.77--0.08) decreased, whereas in mothers, the level of lgTPOAb increased during pregnancy. Positive maternal thyroid peroxidase antibody levels during pregnancy may be associated with poorer cognitive development in preschool children. These findings require independent confirmation in other populations.

Early autism diagnosis based on path signature and Siamese unsupervised feature compressor.

Autism spectrum disorder has been emerging as a growing public health threat. Early diagnosis of autism spectrum disorder is crucial for timely, effective intervention and treatment. However, conventional diagnosis methods based on communications and behavioral patterns are unreliable for children younger than 2 years of age. Given evidences of neurodevelopmental abnormalities in autism spectrum disorder infants, we resort to a novel deep learning-based method to extract key features from the inherently scarce, class-imbalanced, and heterogeneous structural MR images for early autism diagnosis. Specifically, we propose a Siamese verification framework to extend the scarce data, and an unsupervised compressor to alleviate data imbalance by extracting key features. We also proposed weight constraints to cope with sample heterogeneity by giving different samples different voting weights during validation, and used Path Signature to unravel meaningful developmental features from the two-time point data longitudinally. We further extracted machine learning focused brain regions for autism diagnosis. Extensive experiments have shown that our method performed well under practical scenarios, transcending existing machine learning methods and providing anatomical insights for autism early diagnosis.

Srcap haploinsufficiency induced autistic-like behaviors in mice through disruption of Satb2 expression

Mutations in the SRCAP gene are among the genetic alterations identified in autism spectrum disorders (ASD). However, the pathogenic mechanisms remain unclear. In this study, we demonstrate that Srcap+/- mice manifest deficits in social novelty response, as well as increased repetitive behaviors, anxiety, and impairments in learning and memory. Notably, a reduction in parvalbumin-positive neurons is observed in the retrosplenial cortex (RSC) and dentate gyrus (DG) of these mice. Through RNA sequencing, we identify dysregulation in 27 ASD-related genes in Srcap+/- mice. Specifically, we find that Srcap regulates expression of Satb2 via H2A.z in the promoter. Therapeutic intervention via retro-orbital injection of adeno-associated virus (AAV)-Satb2 in neonatal Srcap+/- mice leads to amelioration of the neurodevelopmental and ASD-like abnormalities. Furthermore, the expression of Satb2 only in the RSC of adolescent mice rectifies social novelty impairments. These results underscore the pivotal role of Srcap in neurodevelopment, by regulating Satb2, providing valuable insights for the pathophysiology of ASD.

Neurodevelopment in patients with repaired tetralogy of Fallot.

Neurodevelopmental sequelae are prevalent and debilitating for patients with congenital heart defects. Patients born with tetralogy of Fallot (TOF) are susceptible for abnormal neurodevelopment as they have several risk factors surrounding the perinatal and perioperative period. Some risk factors have been well described in other forms of congenital heart defects, including transposition of the great arteries and single ventricle heart disease, but they have been less studied in the growing population of survivors of TOF surgery, particularly in infancy and childhood. Adolescents with TOF, even without a genetic syndrome, exhibit neuro-cognitive deficits in executive function, visual-spatial skills, memory, attention, academic achievement, social cognition, and problem-solving, to mention a few. They also have greater prevalence of anxiety disorder, disruptive behavior and attention-deficit hyperactivity disorder. These deficits impact their academic performance, social adjustment, and quality of life, thus resulting in significant stress for patients and their families. Further, they can impact their social adjustment, employment and career development as an adult. Infants and younger children can also have significant deficits in gross and fine motor skills, cognitive deficits and abnormal receptive language. Many of the risk factors associated with abnormal neurodevelopment in these patients are not readily modifiable. Therefore, patients should be referred for evaluation and early intervention to help maximize their neurodevelopment and improve overall outcomes. More study is needed to identify potentially modifiable risk factors and/or mediators of neurodevelopment, such as environmental and socio-economic factors.

Classification of Autism Spectrum Disorder using Resting State-Functional Magnetic Resonance Imaging and Artificial Neural Network

Autism Spectrum Disorder (ASD) represents a growing challenge in public health, characterized by irreversible neurodevelopmental abnormalities. Despite a rising prevalence, the underlying aetiology and neural substrates of ASD remain incompletely understood. Resting state-functional Magnetic Resonance Imaging (rs-fMRI) has emerged as a valuable non-invasive tool for probing the organization and cognitive functions of the brain by capturing hemodynamic changes. This study explores the relationship between Functional Connectivity (FC) alterations, measured by rs-fMRI, and the manifestation of ASD-related brain disorders. In this paper, we propose a hybrid approach employing an InfoMax Independent Component Analysis (ICA) algorithm and Artificial Neural Network to distinguish between the ASD subjects and Healthy Controls (HCs). Initially, rs-fMRI datasets are preprocessed using Statistical Parametric Mapping (SPM). Further, these datasets are processed using InfoMax ICA to extract the distinct features such as fractional Amplitude of Low-Frequency Fluctuations (fALFF) and Dynamic Range and visualize the FC alterations by region mapping. In addition to this, the number of activated voxels for each brain regions are estimated to observe the neural abnormalities. Finally, the extracted features are fed as input to train, test and validate the ANN classifier. The efficacy of the proposed network is evaluated using the Autism Brain Imaging Data Exchange (ABIDE) dataset and an accuracy of 75.3 percentage is achieved.

Normative volumes and relaxation times at 3T during brain development

While research has unveiled and quantified brain markers of abnormal neurodevelopment, clinicians still work with qualitative metrics for MRI brain investigation. The purpose of the current article is to bridge the knowledge gap between case-control cohort studies and individual patient care. Here, we provide a unique dataset of seventy-three 3-to-17 years-old healthy subjects acquired with a 6-minute MRI protocol encompassing T1 and T2 relaxation quantitative sequence that can be readily implemented in the clinical setting; MP2RAGE for T1 mapping and the prototype sequence GRAPPATINI for T2 mapping. White matter and grey matter volumes were automatically quantified. We further provide normative developmental curves based on these two imaging sequences; T1, T2 and volume normative ranges with respect to age were computed, for each ROI of a pediatric brain atlas. This open-source dataset provides normative values allowing to position individual patients acquired with the same protocol on the brain maturation curve and as such provides potentially useful quantitative biomarkers facilitating precise and personalized care.

Biomarkers of Brain Dysfunction in Perinatal Iron Deficiency.

Iron deficiency in the fetal and neonatal period (perinatal iron deficiency) bodes poorly for neurodevelopment. Given its common occurrence and the negative impact on brain development, a screening and treatment strategy that is focused on optimizing brain development in perinatal iron deficiency is necessary. Pediatric societies currently recommend a universal iron supplementation strategy for full-term and preterm infants that does not consider individual variation in body iron status and thus could lead to undertreatment or overtreatment. Moreover, the focus is on hematological normalcy and not optimal brain development. Several serum iron indices and hematological parameters in the perinatal period are associated with a risk of abnormal neurodevelopment, suggesting their potential use as biomarkers for screening and monitoring treatment in infants at risk for perinatal iron deficiency. A biomarker-based screening and treatment strategy that is focused on optimizing brain development will likely improve outcomes in perinatal iron deficiency.

De novo variants in GABRA4 are associated with a neurological phenotype including developmental delay, behavioral abnormalities and epilepsy.

Nine out of 19 genes encoding GABAA receptor subunits have been linked to monogenic syndromes characterized by seizures and developmental disorders. Previously, we reported the de novo variant p.(Thr300Ile) in GABRA4 in a patient with epilepsy and neurodevelopmental abnormalities. However, no new cases have been reported since then. Through an international collaboration, we collected molecular and phenotype data of individuals carrying de novo variants in GABRA4. Patients and their parents were investigated either by exome or genome sequencing, followed by targeted Sanger sequencing in some cases. All variants within the transmembrane domain, including the previously reported p.(Thr300Ile) variant, were characterized in silico and analyzed by molecular dynamics (MD) simulation studies. We identified three novel de novo missense variants in GABRA4 (NM_000809.4): c.797 C > T, p.(Pro266Leu), c.899 C > A, p.(Thr300Asn), and c.634 G > A, p.(Val212Ile). The p.(Thr300Asn) variant impacts the same codon as the previously reported variant p.(Thr300Ile) and likely arose post-zygotically as evidenced by sequencing oral mucosal cells. Overlapping phenotypes among affected individuals included developmental delay (4/4), epileptiform EEG abnormalities (3/4), attention deficits (3/4), seizures (2/4), autistic features (2/4) and structural brain abnormalities (2/4). MD simulations of the three variants within the transmembrane domain of the receptor indicate that sub-microsecond scale dynamics differ between wild-type and mutated subunits. Taken together, our findings further corroborate an association between GABRA4 and a neurological phenotype including variable neurodevelopmental, behavioral and epileptic abnormalities.

Effects of Treadmill Training on Gross Motor Function, Spasticity and Gait Speed in Ambulatory Children with Spastic Cerebral Palsy

Background: Cerebral palsy is described as a permanent, non-progressive disorder related to neurodevelopmental abnormalities in an underdeveloped brain which leads to additional brain lesions resulting in secondary motor disturbances and postural abnormalities Objective: To determine the effectiveness of treadmill training on gross motor function, spasticity and gait speed in ambulatory children with spastic cerebral palsy. Methodology: It was a Randomized clinical trial, which was done in Bahria International Hospital, Lahore by convenient sampling technique. A sample size of 50 patients were divided into two groups. Patients in Group A underwent conventional physiotherapy, whereas those in Group B received a specialized treadmill training program tailored for children with spastic cerebral palsy, alongside their standard physical therapy sessions. Result: Our data is normally distributed so wo applied Independent sample t test for between group analysis which shows that mean of group A at baseline is 5.40±0.49 and group B is 5.20±0.76, at 6th weeks group A is 4.80±0.48 and group B is 4.33±.0.88and at 12th weeks group A is 3.93±0.58 and group B is 2.13±0.68.p-value shows that there is no significant difference between two groups at baseline and at 6th weeks but at 12th weeks there is a significant differences as p-value is less than 0.00.Repeated measure ANOVA shows both groups shows significant results but mean difference of treadmill training group were more in all outcome. Conclusion: - Our study concludes that treadmill training, along with physiotherapy, is beneficial for children with spastic cerebral palsy in improving gross motor function, spasticity, and gait speed.

Medication Usage Record-Based Predictive Modeling of Neurodevelopmental Abnormality in Infants under One Year: A Prospective Birth Cohort Study.

Early identification of children with neurodevelopmental abnormality is a major challenge, which is crucial for improving symptoms and preventing further decline in children with neurodevelopmental abnormality. This study focuses on developing a predictive model with maternal sociodemographic, behavioral, and medication-usage information during pregnancy to identify infants with abnormal neurodevelopment before the age of one. In addition, an interpretable machine-learning approach was utilized to assess the importance of the variables in the model. In this study, artificial neural network models were developed for the neurodevelopment of five areas of infants during the first year of life and achieved good predictive efficacy in the areas of fine motor and problem solving, with median AUC = 0.670 (IQR: 0.594, 0.764) and median AUC = 0.643 (IQR: 0.550, 0.731), respectively. The final model for neurodevelopmental abnormalities in any energy region of one-year-old children also achieved good prediction performance. The sensitivity is 0.700 (IQR: 0.597, 0.797), the AUC is 0.821 (IQR: 0.716, 0.833), the accuracy is 0.721 (IQR: 0.696, 0.739), and the specificity is 0.742 (IQR: 0.680, 0.748). In addition, interpretable machine-learning methods suggest that maternal exposure to drugs such as acetaminophen, ferrous succinate, and midazolam during pregnancy affects the development of specific areas of the offspring during the first year of life. This study established predictive models of neurodevelopmental abnormality in infants under one year and underscored the prediction value of medication exposure during pregnancy for the neurodevelopmental outcomes of the offspring.

ZFHX3 variants cause childhood partial epilepsy and infantile spasms with favourable outcomes

BackgroundThe ZFHX3 gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between ZFHX3 variants and epilepsy.MethodsWhole-exome sequencing was...

Comparative Assessment of the Effectiveness of HSP70 / HIF-1α System Modulators after Prenatal Hypoxia

Prenatal hypoxia (PH) poses a significant threat to fetal development and may be responsible for neonatal mortality or neurodevelopmental abnormalities. The proteins HSP70 and HIF-1, which hold a distinct significance in the cellular reaction to PH, can be regarded as potential targets for pharmaceutical interventions aimed at mitigating the repercussions of chronic PH. This study aimed to identify a possible correlation between offspring survival and stages of expression of endogenous neuroprotective factors (HSP70 and HIF-1) after chronic prenatal hypoxia with course administration of potential HSP70 modulators (angiolin, piracetam, thiotriazoline, nicomex, cerebrocurin, tamoxifen, L-arginine, glutoredoxin, HSF-1, and mildronate). In the rat offspring after PH we determined the plasma concentrations of HSP70 and HIF-1 by solid-phase ELISA immunoassay, and the expression of HIF-1 mRNA and HSP70 mRNA by real-time PCR. For the first time, we found a positive correlation between offspring survival after PH and the expression of HIF-1 and HSP70, both in groups without experimental therapy and in groups receiving pharmacological agents. The course administration of HSP70/HIF-1α modulators, especially angiolin (50 mg/kg), cerebrocurin (150 mg/kg), and HSF-1 (50 mg/kg), to rats that underwent PH reduces postnatal lethality, increases blood plasma concentrations of HSP70 and HIF-1α, and positively affects the expression level of HIF-1α mRNA in the rat brain. These drugs can be considered as the most promising drug candidates for new therapeutic strategies of pharmacological correction of the consequences of chronic PH.

Assessment of brain structure and volume reveals neurodevelopmental abnormalities in preterm infants with low-grade intraventricular hemorrhage

There is increasing evidence of abnormal neurodevelopmental outcomes in preterm infants with low-grade intraventricular hemorrhage (IVH). The purpose of the study was to explore whether brain microstructure and volume are associated with neuro-behavioral outcomes at 40 weeks corrected gestational age in preterm infants with low-grade IVH. MR imaging at term-equivalent age (TEA) was performed in 25 preterm infants with mild IVH (Papile grading I/II) and 40 control subjects without IVH. These subjects all had neonatal behavioral neurological assessment (NBNA) at 40 weeks’ corrected age. Microstructure and volume evaluation of the brain were performed by using diffusion kurtosis imaging (DKI) and Synthetic MRI. Correlations among microstructure parameters, volume, and developmental outcomes were explored by using Spearman's correlation. In preterm infants with low-grade IVH, the volume of brain parenchymal fraction (BPF) was reduced. In addition, mean kurtosis (MK), fractional anisotropy (FA), radial kurtosis (RK), axial kurtosis (AK) in several major brain regions were reduced, while mean diffusivity (MD) was increased (P < 0.05). BPF, RK in the cerebellum, MK in the genu of the corpus callosum, and MK in the thalamus of preterm infants with low-grade IVH were associated with lower NBNA scores (r = 0.831, 0.836, 0.728, 0.772, P < 0.05). DKI and Synthetic MRI can quantitatively evaluate the microstructure alterations and brain volumes in preterm infants with low-grade IVH, which provides clinicians with a more comprehensive and accurate neurobehavioral assessment of preterm infants with low-grade IVH.

The association of cumulative vasoactive drugs and neurodevelopmental outcomes in preterm Infants

To assess the effect of cardiovascular medications on the neurodevelopment of preterm infants, as measured by calculated cumulative time of vasoactive-inotropic score (VISct). A retrospective study was conducted on preterm infants who developed significant hypotension defined as a mean BP more than 2SDs below the mean for GA and received treatment with duration > 6 hours for each hypotensive episode, we calculated the vasoactive inotropic score (VIS) and cumulative exposure to cardiovascular medications over time (VISct). The composite Bayley III was reported from the high-risk follow-up clinic for the surviving infants between 18 to 21 months corrected age. VISct was significantly higher in infants with abnormal neurodevelopment. Cognitive Bayley was the most affected component with median (IQR) VISct 882.5(249,2047) versus 309(143,471) (p-value 0.012), followed by language function with VISct 786(261,1563.5), versus 343(106.75,473.75) (p-value 0.016) when those with Bayley III <85 were compared with those with normal Bayley IIIs. High VISct scores may have negative effect on cognitive and language neurodevelopmental outcomes.

Effects of prenatal environmental exposure to pesticides on the neurodevelopment of children in the department of Alto Paraná Paraguay at 34-36 months of age

ABSTRACT Prenatal exposure to pesticides of different chemical groups is associated with an increased risk of anthropometric, neurological, and neurodevelopmental alterations in children. The paper reports an evaluation of the neurodevelopmental, nutritional, and sensory status of a group of children belonging to birth cohorts with and without prenatal environmental exposure to pesticides, in the department of Alto Paraná, from a previously published study. A prospective observational study was conducted. The neurodevelopmental status was evaluated with the Battelle Developmental Inventory Screening test (BDIST). The sensory status was assessed through an ophthalmological examination and an otoacoustic emissions test. A total of 100 children aged 34 to 36 months, of whom only 50 were exposed to pesticides during the prenatal period, were included in the study. Results showed that 45% of the children studied had neurodevelopmental impairments. The cognitive area was the most affected (56%) and the risk of abnormal neurodevelopment was 5.6 times higher in children who had been prenatally exposed to pesticides than in the unexposed. Malnourished children were 4 times more likely to have an abnormal BDIST result. Results suggest that prenatal pesticide exposure is an important risk factor for lower neurodevelopment in children at 34 to 36 months of age, adjusted for socioeconomic factors.

New Therapeutic Targets and Drugs for Schizophrenia Beyond Dopamine D2 Receptor Antagonists.

Schizophrenia is a disease with a complex pathological mechanism that is influenced by multiple genes. The study of its pathogenesis is dominated by the dopamine hypothesis, as well as other hypotheses such as the 5-hydroxytryptamine hypothesis, glutamate hypothesis, immune-inflammatory hypothesis, gene expression abnormality hypothesis, and neurodevelopmental abnormality hypothesis. The first generation of antipsychotics was developed based on dopaminergic receptor antagonism, which blocks dopamine D2 receptors in the brain to exert antipsychotic effects. The second generation of antipsychotics acts by dual blockade of 5-hydroxytryptamine and dopamine receptors. From the third generation of antipsychotics onwards, the therapeutic targets for antipsychotic schizophrenia expanded beyond D2 receptor blockade to explore D2 receptor partial agonism and the antipsychotic effects of new targets such as D3, 5-HT1A, 5-HT7, and mGlu2/3 receptors. The main advantages of the second and third generation antipsychotics over first-generation antipsychotics are the reduction of side effects and the improvement of negative symptoms, and even though third-generation antipsychotics do not directly block D2 receptors, the modulation of the dopamine transmitter system is still an important part of their antipsychotic process. According to recent research, several receptors, including 5-hydroxytryptamine, glutamate, γ-aminobutyric acid, acetylcholine receptors and norepinephrine, play a role in the development of schizophrenia. Therefore, the focus of developing new antipsychotic drugs has shifted towards agonism or inhibition of these receptors. Specifically, the development of NMDARs stimulants, GABA receptor agonists, mGlu receptor modulators, cholinergic receptor modulators, 5-HT2C receptor agonists and alpha-2 receptor modulators has become the main direction. Animal experiments have confirmed the antipsychotic effects of these drugs, but their pharmacokinetics and clinical applicability still require further exploration. Research on alternative targets for antipsychotic drugs, beyond the dopamine D2 receptor, has expanded the potential treatment options for schizophrenia and gives an important way to address the challenge of refractory schizophrenia. This article aims to provide a comprehensive overview of the research on therapeutic targets and medications for schizophrenia, offering valuable insights for both treatment and further research in this field.

TBC1D23 mediates Golgi-specific LKB1 signaling

Liver kinase B1 (LKB1), an evolutionarily conserved serine/threonine kinase, is a master regulator of the AMPK subfamily and controls cellular events such as polarity, proliferation, and energy homeostasis. Functions and mechanisms of the LKB1-AMPK axis at specific subcellular compartments, such as lysosome and mitochondria, have been established. AMPK is known to be activated at the Golgi; however, functions and regulatory mechanisms of the LKB1-AMPK axis at the Golgi apparatus remain elusive. Here, we show that TBC1D23, a Golgi-localized protein that is frequently mutated in the neurodevelopment disorder pontocerebellar hypoplasia (PCH), is specifically required for the LKB1 signaling at the Golgi. TBC1D23 directly interacts with LKB1 and recruits LKB1 to Golgi, promoting Golgi-specific activation of AMPK upon energy stress. Notably, Golgi-targeted expression of LKB1 rescues TBC1D23 deficiency in zebrafish models. Furthermore, the loss of LKB1 causes neurodevelopmental abnormalities in zebrafish, which partially recapitulates defects in TBC1D23-deficient zebrafish, and LKB1 sustains normal neuronal development via TBC1D23 interaction. Our study uncovers a regulatory mechanism of the LKB1 signaling, and reveals that a disrupted Golgi-LKB1 signaling underlies the pathogenesis of PCH.

Heterozygous CAPZA2 mutations cause global developmental delay, hypotonia with epilepsy: a case report and the literature review.

CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.

Differences in Motor Development between Preterm Infants and Full-Term Preschool Children.

Although advances in obstetric and neonatal care have improved the survival of preterm infants, many studies document the increased risk of motor and sensory neurodevelopmental abnormalities that can hinder school progress. The aim of this study was to analyze the differences in gross and fine motor development in children born preterm and full term aged 3 to 6 years using the Peabody Developmental Motor Scales 2 (PDMS-II). Fifteen preterm and fifteen term children, matched for age and sex, participated in this study. They were evaluated with the PDMS-II scale. The scores obtained in the PDMS-II scale showed statistically significant differences (p < 0.05) in all subscales except for the "grasping" subscale. No dissimilarities were found between children who attended an early intervention program and those who did not participate, nor was there any correlation between week of gestation and birth weight and motor development in preschool. The results obtained show that differences are found with respect to motor development, with lower scores for those born preterm compared to children born at term. No statistically significant difference was found between preterm children who attended early intervention and those who did not. No correlation was found between motor development at preschool age and birth weight and gestational age.

A Homozygous PTRHD1 Missense Variant (p.Arg122Gln) in an Individual with Intellectual Disability, Generalized Epilepsy, and Juvenile Parkinsonism.

Biallelic variants in PTRHD1 have been associated with autosomal recessive intellectual disability, spasticity, and juvenile parkinsonism, with few reported cases. Here, we present the clinical and genetic findings of a female of Austrian origin exhibiting infantile neurodevelopmental abnormalities, intellectual disability, and childhood-onset parkinsonian features, consistent with the established phenotypic spectrum. Notably, she developed genetic generalized epilepsy at age 4, persisting into adulthood. Using diagnostic exome sequencing, we identified a homozygous missense variant (c.365G > A, p.(Arg122Gln)) in PTRHD1 (NM_001013663). In summary, our findings not only support the existing link between biallelic PTRHD1 variants and parkinsonism with neurodevelopmental abnormalities but also suggest a potential extension of the phenotypic spectrum to include generalized epilepsy.