Delayed Language Development Research Articles

Developmental, Cognitive, Ocular Motor, and Neuroimaging Findings Related to SUFU Haploinsufficiency: Unraveling Subtle and Highly Variable Phenotypes

BackgroundBiallelic SUFU variants have originally been linked to Joubert syndrome, comprising cerebellar abnormalities, dysmorphism, and polydactyly. In contrast, heterozygous truncating variants have recently been associated with developmental delay and ocular motor apraxia, but only a limited number of patients have been reported. Here, we aim to delineate further the mild end of the phenotypic spectrum related to SUFU haploinsufficiency. MethodsNine individuals (from three unrelated families) harboring truncating SUFU variants were investigated, including two previously reported individuals (from one family). We provide results from a comprehensive assessment comprising neuroimaging, neuropsychology, video-oculography, and genetic testing. ResultsWe identified three inherited or de novo truncating variants in SUFU (NM_016169.4): c.895C>T p.(Arg299∗), c.71dup p.(Ala25Glyfs∗23), and c.71del p.(Pro24Argfs∗72). The phenotypic expression showed high variability both between and within families. Clinical features include motor developmental delay (seven of nine), axial hypotonia (five of nine), ocular motor apraxia (three of nine), and cerebellar signs (three of nine). Four of the six reported children had macrocephaly. Neuropsychological and developmental assessments revealed mildly delayed language development in the youngest children, whereas general cognition was normal in all variant carriers. Subtle but characteristic SUFU-related neuroimaging abnormalities (including superior cerebellar dysplasia, abnormalities of the superior cerebellar peduncles, rostrally displaced fastigium, and vermis hypoplasia) were observed in seven of nine individuals. ConclusionsOur data shed further light on the mild but recognizable features of SUFU haploinsufficiency and underline its marked phenotypic variability, even within families. Notably, neurodevelopmental and behavioral abnormalities are mild compared with Joubert syndrome and seem to be well compensated over time.

Early Symptoms and Treatment Outcomes in Neuronal Ceroid Lipofuscinosis Type 2: Croatian Experience.

Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare neurodegenerative disease that generally appears in children between 2 and 4 years old, leading to seizures and a progressive loss of language and motor functions. As the disease progresses, affected individuals typically experience blindness and ultimately pass away in late childhood. Treatment with intracerebroventricular cerliponase alfa has been shown to slow the deterioration of motor and language functions compared to the natural progression of the disease. We aim to highlight the early symptoms of CLN2 which help with early diagnosis and timely treatment initiation in children with specific medical indications, as well as identify medical contraindications for enzyme replacement therapy. We describe five Croatian patients and one Bosnia and Herzegovinian patient with CLN2 disease, analyzing the clinical characteristics, neuroimaging findings, electroencephalogram results, genetic analysis, treatment indications and contraindications, and disease progression. All six patients presented with seizures: focal seizures (n = 1), myoclonic-atonic seizures (n = 1), febrile seizures (n = 2), and tonic-clonic seizures (n = 2), along with language delay (n = 6). Despite this, one patient refused treatment, two were initially included in the clinical trial and then continued treatment, one did not indicate starting treatment, and three continued treatment. One patient, after 4.5 years of treatment, no longer had medical indications for the therapy, which was discontinued. The other two patients who received treatment had a significant slowing of disease progression. The early onset of seizures between ages 2 and 4, alongside delayed language development, is a defining characteristic of CLN2 disease. Enzyme replacement therapy using cerliponase alfa represents the initial treatment for neuronal ceroid lipofuscinosis type 2, targeting the underlying cause of the disease. It effectively delays the progression of language and motor decline in patients diagnosed with this condition.

The association between screen time exposure, parent depression, and development of social communication skills among preschool children in Qassim Region

BackgroundScreen exposure among children continues to increase worldwide. It has negative effects on children of developmental age, including obesity, poor attention, sleep disorders, vision problems, language delays, and deficits in communication skills. It has been reported that parental depression is associated with both increased screen time for children and poor function and skills in children. However, other studies have reported no association between screen time and parental depression.Research methodologyA cross-sectional study was conducted using a convenience sample of 340 parents of 4- to 6-year-old children in the Qassim Region of Saudi Arabia. Data were collected from the primary health care vaccination clinic by contacting parents of children aged 4 to 6 years to fill out the Social Communication Questionnaire (SCQ) for the child and the Patient Health Questionnaire-9 (PHQ9) for the parents.Research resultsWe conducted a regression analysis to assess the influence of screen time exposure on social communication skills (SCQ score). The results of this study indicated that there was no significant effect observed (B = 0.283, P > 0.05), indicating that a positive correlation between screen time usage and SCQ score may not apply to the entire population. Conversely, we discovered a crucial link between screen time exposure and parental depression (PHQ), as it displayed noteworthy impact values (B = 1.136, P < 0.05), indicating an affirmative correlation between them. In addition, our results also indicated apparent positive associations between parental depression and SCQ scores (B = 0.229, P < 0.05).ConclusionOur findings revealed that there was a significant association between parental depression and both screen time exposure and SCQ score, while there was no correlation between screen time exposure and SCQ score.

Перинатальні особливості при рецидивній герпесвірусній інфекції

The aim of the study is to determine perinatal features in recurrent herpesvirus infection (HVI). Materials and methods. 160 pregnant women and their newborns were examined: 100 women with recurrence during pregnancy of herpes simplex virus type 1 and/or 2 (HSV-1 and/or HSV-2), 30 women seropositive for HSV-1 and/or HSV-2 without relapse during pregnancy, 30 women seronegative for HVI. Peculiarities of the perinatal period and the development of children at 1 year of life were studied. The obtained data were processed by the methods of variational statistics, using the Student's t-test and Fisher's angular transformation. The Microsoft Excel statistical analysis package was used. Results. Recurrent HVI during pregnancy is associated with a significantly increased frequency of pregnancy complications (threat of abortion in 52.0% of women, threat of premature birth in 21.0%, anemia of pregnancy in 54.0%, placental insufficiency in 72.0%, fetal distress in 24.0%), childbirth (abnormalities of labor in 28.0%, fetal distress in 15.0%), postpartum blood loss (5.0%). Children are more often born prematurely (6.0%), in a state of asphyxia (24.0%), with reduced body weight (28.0%). In the structure of complications of the neonatal period, infections typical for the perinatal period, damage to the nervous system, respiratory distress syndrome prevail. In the period of life up to 1 year, a quarter of children belong to the group of frequently and long-term patients, 14.0% are underweight, and a third are overweight. One third had anemia, 14.0% had exudative diathesis, 24.0% had a syndrome of movement disorders and increased neuro-reflex excitability. Delayed motor development in combination with delayed reduction of muscle tone, delayed language development, game skills, and communication skills were noted. Conclusions. Recurrent HVI during pregnancy causes a high frequency of perinatal disorders, which requires preconception counseling and pregnancy management in order to avoid recurrences of GVI, prevent stressful situations, join infections, and correct the psycho-emotional state. The study was carried out in accordance with the main provisions of GCP ICH and the Declaration of Helsinki, agreed with the Local Ethics Committee of the institution. All studies were performed after obtaining the informed consent of the women. The authors declare no conflict of interest.

Parents reported language development and scholastic achievement in children with congenital heart diseases versus typically developed

BackgroundChildren with congenital heart diseases (CHD) may have developmental delays including delayed language development (DLD) and learning difficulties. The purpose of this study was to observe the effects of CHD on language developmental profile and scholastic achievement (SA) with particular emphasis on prevalence of DLD and SA, potential risks, and need for early intervention.ResultsThis case–control study included 158 children with CHD and 145 healthy children as controls. Participants’ ages ranged from 6 months to 15 years. Data were collected by reviewing clinical records and questionnaires covering potential risks, motor and language development, and SA. Potential risks were analyzed using the Fisher test, while language development and SA were compared using Mann–Whitney test. The incidences of parent consanguinity, family history of DLD, and neonatal cyanosis were higher than expected by chance in the CHD group with p-values which are < 0.001, 0.044, and < 0.001, respectively. The CHD group revealed more delay in babbling, first word production, two-word sentences, three-word sentences, narration, and SA than control group with significant differences. These comparisons’ p-values are 0.002, < 0.001, 0.009, 0.029, 0.03, and 0.042 respectively with mean effect size 0.3. The language development profile in cyanotic HD showed more delay than acyanotic HD with significant differences.ConclusionsThe DLD and affected SA were more prevalent in children with CHD. The risk for DLD in CHD children was multifactorial; however, the main predisposing factor was chronic hypoxia that starts in the intrauterine life in CHD. Neonates with CHD require early intervention through oxygen therapy before surgery. Early family counseling and language therapy are recommended to improve quality of life through achieving better communicative ability and academic skills. Further studies which concerned the effect of maternal oxygenation on prognosis of fetuses with CHD may be required. Also, duplication of the study including formal testing is recommended.

Association between Sleep and Language Development in Children with Congenital Zika Syndrome.

Congenital Zika Virus Syndrome (CZS) presents notable hurdles to neurodevelopment, with language development emerging as a crucial aspect. This study investigates sleep patterns and language skills in children with CZS, aiming to explore the potential synchronization of sleep development with their neurodevelopment. We studied cross-sectionally 135 children with CZS aged 0 to 48 months, investigating sleep using the BISQ Questionnaire. Language development was assessed using the Early Language Milestone Scale, while motor development and cognitive and social ability were assessed using the Bayley Scales of Infant and Young Child Development 3rd edition. We also studied longitudinally a cohort of 16 children (initially aged 0 to 12 months) whom we followed for four years, assessing at one-year intervals. Sleep disturbances and language deficits were highly frequent in this population. In the 0-12 months group, a late bedtime and frequent nighttime awakenings were associated with poorer auditory expressive skills. At 13-24 months, nighttime awakenings were associated with poorer auditory expressive skills, while among 25-36-month-olds decreased auditory receptive skills were associated with longer sleep onset latency and reduced nighttime sleep duration. The brain alterations caused by Zika virus infection affect both sleep disturbances and delays in language development. It is possible that sleep disturbance may be a mediating factor in the pathway between CZS and delayed language development, as the three analyzed language skills showed a correlation with sleep parameters.

Children at Risk of Specific Learning Disorder: A Study on Prevalence and Risk Factors.

Specific learning disorder (SLD) is a neurodevelopmental condition characterised by significant academic difficulties despite normal intelligence and adequate education. The difficulties with reading, writing, and arithmetic may manifest independently or concurrently at different ages. Early symptoms may appear in preschool, including delays in social skills, motor skills, and language development. This study aimed to assess the prevalence of preschool children at risk for SLD and related psychiatric disorders. Data were collected from 515 preschool children in Edirne City, Turkey, using a screening scale for early symptoms of SLD. Socio-demographic information was obtained, and children at risk were invited for a psychiatric evaluation. The mean age of the participants was 72.5 ± 5.6 months. It was determined that 5.7% of the preschool children who participated in the questionnaire were at risk of SLD according to the screening scale scores. Factors such as a father's low education, the mother smoking during pregnancy, a longer stay in the neonatal intensive care unit, longer screen time, and consanguinity between parents were associated with an increased risk of SLD. This study emphasises the importance of early identification and intervention for SLD and the need to consider associated psychiatric comorbidities. Identifying the risk factors in preschool children may facilitate timely intervention and prevent academic and social difficulties in later years.

Learning Media "ARASIK" in Understanding the Meaning of Nouns for SDLB Deaf Students at SLB Negeri Bogor

Deaf children experience speech and language difficulties due to hearing loss. Children with hearing loss experience delays and communication difficulties due to delays in speech and language development. The main problem in language acquisition for deaf children is that they have difficulty understanding the meaning of words. The problem is that children can read, but they do not understand what they read. The title of this article is ``The learning media "ARASIK" in understanding the meaning of nouns in SDLB Deaf students at SLB Negeri Bogor" The theoretical foundations used in this study are: (1) understanding the meaning of words, as stated by Nurbeiti Jamalus that the meaning of a word is the relationship between the sound (language) of the word spoken or written with the object concerned; (2) Augmented Realitiy learning media promoted by scientists, that AR can visualize abstract concepts for understanding and the structure of an object model allows AR as a more effective media in accordance with the objectives of learning media. This research uses a descriptive-qualitative approach, with data collection techniques through observation, interviews and documentation studies. The data analysis technique used refers to Miles and Huberman (1994) which includes three activities, namely: (1) data reduction, (2) data presentation, and (3) conclusion drawing from the application of "ARASIK" media. Based on the results of the study, it can be concluded that the "ARASIK" media can help facilitate SDLB Deaf students in understanding the meaning of nouns.

FBXO11 variants are associated with intellectual disability and variable clinical manifestation in Chinese affected individuals.

F-box protein 11 (FBXO11) is a member of F-Box protein family, which has recently been proved to be associated with intellectual developmental disorder with dysmorphic facies and behavioral abnormalities (IDDFBA, OMIM: 618089). In this study, 12 intellectual disability individuals from 5 Chinese ID families were collected, and whole exome sequencing (WES), sanger sequencing, and RNA sequencing (RNA-seq) were conducted. Almost all the affected individuals presented with mild to severe intellectual disability (12/12), global developmental delay (10/12), speech and language development delay (8/12) associated with a range of alternate features including increased body weight (7/12), short stature (6/12), seizures (3/12), reduced visual acuity (4/12), hypotonia (1/12), and auditory hallucinations and hallucinations (1/12). Distinguishingly, malformation was not observed in all the affected individuals. WES analysis showed 5 novel FBXO11 variants, which include an inframe deletion variant, a missense variant, two frameshift variants, and a partial deletion of FBXO11 (exon 22-23). RNA-seq indicated that exon 22-23 deletion of FBXO11 results in a new mRNA structure. Conservation and protein structure prediction demonstrated deleterious effect of these variants. The DEGs analysis revealed 148 differentially expressed genes shared among 6 affected individuals, which were mainly associated with genes of muscle and immune system. Our research is the first report of FBXO11-associated IDDFBA in Chinese individuals, which expands the genetic and clinical spectrum of this newly identified NDD/ID syndrome.

Home Musical Activities Boost Premature Infants' Language Development.

Infants born prematurely are considered at risk for language development delay and impairments. Using online parental reports, the present study investigated the influence of early musical experience in the home environment (Music@Home Infant Questionnaire) on language development (MacArthur-Bates Communicative Development Inventory) while controlling for general enrichment at home (Stim-Q Cognitive Home Environment Questionnaire) and perinatal post-traumatic stress disorder (Perinatal PTSD Questionnaire). Caregivers of 117 infants between 8 and 18 months of age (corrected age) without reported developmental difficulties completed an online survey. Results revealed that the musical home environment significantly predicted outcomes in reported infants' receptive vocabulary and gestural communication, independently from infants' corrected age and general enrichment of home activities. These findings constitute the first evidence that an enriched musical experience can enhance the development of early communication skills in a population at risk for language delays, namely infants born prematurely, opening the path for future intervention research in home and/or early childcare settings. Given that the majority of participants in this study were highly educated and from socioeconomically stable backgrounds, considerations regarding the generalizability of these results are discussed.

Clinical and molecular outcomes from the 5-Year natural history study of SSADH Deficiency, a model metabolic neurodevelopmental disorder

BackgroundSuccinic semialdehyde dehydrogenase deficiency (SSADHD) represents a model neurometabolic disease at the fulcrum of translational research within the Boston Children’s Hospital Intellectual and Developmental Disabilities Research Centers (IDDRC), including the NIH-sponsored natural history study of clinical, neurophysiological, neuroimaging, and molecular markers, patient-derived induced pluripotent stem cells (iPSC) characterization, and development of a murine model for tightly regulated, cell-specific gene therapy.MethodsSSADHD subjects underwent clinical evaluations, neuropsychological assessments, biochemical quantification of γ-aminobutyrate (GABA) and related metabolites, electroencephalography (standard and high density), magnetoencephalography, transcranial magnetic stimulation, magnetic resonance imaging and spectroscopy, and genetic tests. This was parallel to laboratory molecular investigations of in vitro GABAergic neurons derived from induced human pluripotent stem cells (hiPSCs) of SSADHD subjects and biochemical analyses performed on a versatile murine model that uses an inducible and reversible rescue strategy allowing on-demand and cell-specific gene therapy.ResultsThe 62 SSADHD subjects [53% females, median (IQR) age of 9.6 (5.4–14.5) years] included in the study had a reported symptom onset at ∼ 6 months and were diagnosed at a median age of 4 years. Language developmental delays were more prominent than motor. Autism, epilepsy, movement disorders, sleep disturbances, and various psychiatric behaviors constituted the core of the disorder’s clinical phenotype. Lower clinical severity scores, indicating worst severity, coincided with older age (R= -0.302, p = 0.03), as well as age-adjusted lower values of plasma γ-aminobutyrate (GABA) (R = 0.337, p = 0.02) and γ-hydroxybutyrate (GHB) (R = 0.360, p = 0.05). While epilepsy and psychiatric behaviors increase in severity with age, communication abilities and motor function tend to improve. iPSCs, which were differentiated into GABAergic neurons, represent the first in vitro neuronal model of SSADHD and express the neuronal marker microtubule-associated protein 2 (MAP2), as well as GABA. GABA-metabolism in induced GABAergic neurons could be reversed using CRISPR correction of the pathogenic variants or mRNA transfection and SSADHD iPSCs were associated with excessive glutamatergic activity and related synaptic excitation.ConclusionsFindings from the SSADHD Natural History Study converge with iPSC and animal model work focused on a common disorder within our IDDRC, deepening our knowledge of the pathophysiology and longitudinal clinical course of a complex neurodevelopmental disorder. This further enables the identification of biomarkers and changes throughout development that will be essential for upcoming targeted trials of enzyme replacement and gene therapy.

Clinical and neurodevelopmental predictors of psychotic disorders in children and adolescents at clinical high risk for psychosis: the CAPRIS study.

The neurodevelopmental hypothesis of schizophrenia represents the disorder as an expression of an alteration during the brain development process early in life. Neurodevelopmental variables could become a trait marker, and the study of these variables in children and adolescents at clinical high risk for psychosis (CHR) could identify a specific cluster of patients who later developed psychosis. The aim of this study is to describe clinical and neurodevelopment predictors of transition to psychosis in child and adolescent participants at CHR.Naturalistic longitudinal two-center study of 101 CHR and 110 healthy controls (HC) aged 10-17. CHR participants were children and adolescents aged 10-17, meeting one or more of the CHR criteria assessed at baseline and at 18 months' follow-up. Neurodevelopmental variables assessed were obstetric complications, delay in principal development milestones, and presence of a neurodevelopment diagnosis. Pairwise comparisons, linear regressions, and binary logistic regression were performed.A transition rate of 23.3% at 1.5 years was observed. Participants who developed psychosis (CHR-P) showed higher rates of grandiosity and higher proportions of antipsychotic medication intake at baseline compared to participants who did not develop a psychotic disorder (CHR-NP). In terms of neurodevelopment alterations, CHR-P group showed a higher proportion of participants reporting delay in language development than the CHR-NP and HC groups. The odds of psychosis increased by 6.238 CI 95% [1.276-30.492] for a one-unit increase in having a positive score in grandiosity; they increased by 4.257 95% CI [1.293-14.023] for a one-unit increase in taking antipsychotic medication, and by 4.522 95% [1.185-64.180] for showing language development delay. However, the p-values did not reach significance after adjusting for multiple comparisons.A combination of clinical and neurodevelopmental alterations could help predict the transition to psychotic disorder in a CHR child and adolescent sample. Our results suggest the potential utility of collecting information about neurodevelopment and using these variable multifactorial models to predict psychosis disorders.

Telepractice Parent Training of Enhanced Milieu Teaching With Phonological Emphasis (EMT+PE) For Persian-Speaking Toddlers With Nonsyndromic Cleft Palate: Protocol for a Randomized Controlled Trial.

Children born with a cleft palate with or without a cleft lip (CP/L) are at increased risk for delayed language development and speech sound disorders. Enhanced Milieu Teaching with Phonological Emphasis (EMT+PE) is a recommended naturalistic intervention for toddlers with CP/L. The parents' role in providing naturalistic interventions is critical and they need training based on learning principles to implement these interventions. Telepractice is an appropriate method for training parents and children with various speech-related disorders. This study aims to determine and compare the effectiveness of telepractice and the parent-implemented EMT+PE intervention on language and speech measures in toddlers with CP/L with usual interventions and determine the effectiveness maintenance of the intervention. A randomized controlled trial (RCT) will assess the efficacy of telepractice and the parent-implemented EMT+PE intervention in enhancing speech and language measures in toddlers with CP/L. Eligible participants will be randomly assigned to one of 2 groups: the conventional intervention group and the EMT+PE intervention group. Participants' speech and language measures will be evaluated remotely by trained raters before and after the intervention and 2 months after the intervention. Parents of participants in the intervention group will receive 3 months of training in speech and language supportive strategies from trained therapists using telehealth fidelity scales. Parents of participants in the control group will receive the conventional speech and language intervention by cleft team therapists. Study outcomes will include language variables (mean length of utterance) and speech production variables (percent correct consonants). The protocol was approved by the Research Ethics Committee of the University of Social Welfare and Rehabilitation Sciences in February 2022. The selection process of participants, as well as training therapists and raters, commenced in January 2022, the therapy and follow-up period ended in June 2023, and pre- and postintervention assessments have been conducted. Data analysis is ongoing, and we expect to publish our results by the summer of 2024. Funding is yet to be received. The results of this study may help us develop a speech and language intervention with a different delivery model for toddlers with CP/L, and the cleft team care can use these results in service delivery. Consistent with our hypothesis, speech and language measures are expected to improve. DERR1-10.2196/54426.

The impact of poverty and socioeconomic status on brain, behaviour, and development: a unified framework.

In this article, we, for the first time, provide a comprehensive overview and unified framework of the impact of poverty and low socioeconomic status (SES) on the brain and behaviour. While there are many studies on the impact of low SES on the brain (including cortex, hippocampus, amygdala, and even neurotransmitters) and behaviours (including educational attainment, language development, development of psychopathological disorders), prior studies did not integrate behavioural, educational, and neural findings in one framework. Here, we argue that the impact of poverty and low SES on the brain and behaviour are interrelated. Specifically, based on prior studies, due to a lack of resources, poverty and low SES are associated with poor nutrition, high levels of stress in caregivers and their children, and exposure to socio-environmental hazards. These psychological and physical injuries impact the normal development of several brain areas and neurotransmitters. Impaired functioning of the amygdala can lead to the development of psychopathological disorders, while impaired hippocampus and cortex functions are associated with a delay in learning and language development as well as poor academic performance. This in turn perpetuates poverty in children, leading to a vicious cycle of poverty and psychological/physical impairments. In addition to providing economic aid to economically disadvantaged families, interventions should aim to tackle neural abnormalities caused by poverty and low SES in early childhood. Importantly, acknowledging brain abnormalities due to poverty in early childhood can help increase economic equity. In the current study, we provide a comprehensive list of future studies to help understand the impact of poverty on the brain.

Cost-effectiveness of Neonatal Hearing Screening Programs: Systematic Review.

Introduction Universal newborn hearing screening (UNHS) has been widely and strongly advocated as an early detection strategy for hearing loss in children. This intervention aims to prevent delays in speech and language development, which, in turn, has long-term beneficial effects on the social and emotional development and quality of life of individuals. However, the implementation of UNHS programs is circumstantial in different settings, for different reasons. Objectives The present systematic review aimed to identify whether the implementation of UNHS programs are cost-effective, as well as their variations by localities. Data Synthesis A search was conducted in seven databases: PubMed (Medline), Scopus, Web of Science, Embase, CINAHL, Lilacs, and Cochrane Library. Studies that included a cost analysis of UNHS programs were eligible for inclusion. Studies on evaluations of preschool or school-based programs only were excluded, among others. A total of 1,291 records were found. Of these, 23 articles were analyzed in full. All articles identified the cost-effectiveness of the UNHS programs implemented. Regarding the UNHS protocols, a wide variation was observed in all aspects: tests used, period established between tests and retests, professionals responsible for screening, environment, and criteria for defining hearing loss, limiting the generalization of this information. All studies presented values related to the expenses with the program, but none of them showed statistical elements for the described analyzes or any theoretical basis for such. Conclusion It is necessary to estimate local specific issues, as well as the accuracy of the chosen tests and the NHS protocols used, so that more accurate analyzes on cost-effectiveness are possible.

SYNGAP1-related developmental and epileptic encephalopathy: Genotypic and phenotypic characteristics and longitudinal insights.

The clinical and genetic characteristics of SYNGAP1 mutations in Korean pediatric patients are not well understood. We retrospectively analyzed 13 individuals with SYNGAP1 mutations from a longitudinal aspect. Clinical data, genetic profiles, and electroencephalography (EEG) patterns were examined. Genotypic analyses included gene panels and whole-exome sequencing. All patients exhibited global developmental delay from early infancy, with motor development eventually reaching independent ambulation by 3 years of age. Language developmental delay varied significantly from nonverbal to simple sentences, which plateaued in all patients. Patients with the best language outcomes typically managed 2-3-word sentences, corresponding to a developmental age of 2-3 years. Epilepsy developed in 77% of patients, with onset consistently following developmental delays at a median age of 31 months. Longitudinal EEG data revealed a shift from occipital to frontal epileptiform discharges with age, suggesting a correlation with synaptic maturation. These findings suggest that the critical developmental plateau occurs between the ages of 2 and 5 years and is potentially influenced by epilepsy. By analyzing longitudinal data, our study contributes to a deeper understanding of SYNGAP1-related DEE, provides potential EEG biomarkers, and underlines the importance of early diagnosis and intervention to address this complex disorder.

Deficiency of the paternally-expressed imprinted Peg3 gene in mice has sexually dimorphic consequences for offspring communication and social behaviour.

Imprinted genes are expressed from one parental allele as a consequence of epigenetic processes initiated in the germline. Consequently, their ability to influence phenotype depends on their parent-of-origin. Recent research suggests that the sex of the individual expressing the imprinted gene is also important. We have previously reported that genetically wildtype (WT) dams carrying and caring for pups mutant for PEG3 exhibit anxiety-like behaviours and their mutant pups show a reduction in ultrasonic vocalisation when separated from their mothers. Sex-specificity was not examined. WT female mice were mated with WT, heterozygous Peg3-/+ or homozygous Peg3-/- studs to generate all WT (control), 50:50 mixed or 100% mutant litters, respectively, followed by behavioural assessment of both dams and their pups. We reproduced our original finding that WT dams carrying and caring for 100% mutant litters exhibit postpartum anxiety-like symptoms and delayed pup retrieval. Additionally, these WT dams were found to allocate less time to pup-directed care behaviours relative to controls. Male Peg3-deficient pups demonstrated significantly reduced vocalisation with a more subtle communication deficit in females. Postweaning, male mutants exhibited deficits across a number of key social behaviours as did WT males sharing their environment with mutants. Only modest variations in social behaviour were detected in experimental females. We have experimentally demonstrated that Peg3 deficiency confined to the offspring causes anxiety in mouse mothers and atypical behaviour including deficits in communication in their male offspring. A male-specific reduction in expression PEG3 in the fetally-derived placenta has previously been associated with maternal depression in human pregnancy. Maternal mood disorders such as depression and anxiety are associated with delays in language development and neuroatypical behaviour more common in sons. Peg3 deficiency could drive the association of maternal and offspring behavioural disorders reported in humans.

Co-occurrence of delayed language development and autism spectrum disorder in children with metabolic disorders

BackgroundChildren with various metabolic disorders are considered a high-risk group for different developmental delays. Delayed language development (DLD) and autism spectrum disorder (ASD) have a common incidence in children with metabolic disorders which negatively impact their social and academic life. So, early assessment of this high-risk group for the presence of DLD and/or ASD is of great significance and providing better prognosis through starting therapy as early as possible.Aim of the workIt aims to detect the presence of DLD and ASD among children with metabolic disorders.MethodsThis is an analytical (observational) cross-sectional study. The subjects of this study comprised a convenient sample of 100 children diagnosed as having different metabolic disorders with age range between 24 and 48 months. The Modified Preschool Language Scale, Fourth Edition–Arabic version and the Childhood Autism Rating Scale were applied for all children, to detect the presence of DLD and ASD.ResultsAssessment of 100 children with unequal distribution of 13 types of metabolic disorders found that 86% of cases had DLD and 16% had ASD. Regarding different metabolic disorders, we found both DLD and ASD in nine types and only DLD in four types of metabolic disorders.ConclusionChildren with metabolic disorders are at a high risk for DLD and ASD. Early detection of these cases provides early intervention and better outcome.

Clinical practice guideline: Interventions for Developmental Language Delay and Disorders.

Approximately 9.9 % of children present with difficulties in language development (DLD), 7.6 % without serious additional impairments and 2.3 % associated with languagerelevant comorbidities, e.g., hearing loss. Notably, in a consensus statement by experts in German-speaking countries, in the guideline presented here, and further in this article, all of these disorders are referred to as "developmental language disorders" (DLD), whereas the international consortium CATALISE only refers to those without comorbidities as DLD. DLDs are among the most commonly treated childhood disorders and, if persistent, often reduce educational and socio-economic outcome. Children in their third year of life with developmental language delay (late talkers, LT) are at risk of a later DLD. This German interdisciplinary clinical practice guideline reflects current knowledge regarding evidence-based interventions for developmental language delay and disorders. A systematic literature review was conducted on the effectiveness of interventions for DLD. The guideline recommends parent training (Hedges g = 0.38 to 0.82) for LTs with expressive language delay, language therapy (Cohen's d = -0.20 to 0.90) for LTs with additional receptive language delay or further DLD risk factors, phonological or integrated phonological treatment methods (Cohen's d = 0.89 to 1.04) for phonological speech sound disorders (SSDs), a motor approach for isolated phonetic SSDs (non-DLD), and for lexical-semantic and morpho-syntactic impairments combinations of implicit and explicit intervention approaches (including input enrichment, modeling techniques, elicitation methods, creation of production opportunities, metalinguistic- approaches, visualizations; Cohen's d = 0.89-1.04). Recom mendations were also made for DLD associated with pragmatic-communicative impairment, bi-/ multilingualism, hearing loss, intellectual disability, autism-spectrum disorders, selective mutism, language- relevant syndromes or multiple disabilities, and for intensive inpatient language rehabilitation. Early parent- and child-centered speech and language intervention implementing evidence-based intervention approaches, frequency, and settings, combined with educational language support, can improve the effectiveness of management of developmental language delay and disorders.

Overview Study on Language Development for Preschool Children on Scopus Database

This study aims to conduct an overview study of language development for preschool children based on the Scopus database. We apply the PRISMA model to select academic journals. The authors analyzed information such as the number of research papers, countries, authors, citations, keywords, and issues of interest to researchers regarding language development for preschool children. The findings revealed a significant increase in the number of articles on language development for preschool children in the Scopus database between 2021 and 2022, with a substantial proportion originating from American research papers. Researchers have been interested in many issues in the field of language development for preschool children, including updated issues such as the problem of delayed language development and the impact of information and communication technology on children..... With the findings from this article, researchers, preschool teachers, parents and people interested in education can grasp important information about language development for preschool children, thereby orienting research or implementing educational goals for language development for preschool children in the future.