The Angelman Syndrome Video Assessment (ASVA) is a clinician-reported outcome measure that was developed to assess the functional ability of individuals with Angelman Syndrome (AS) in a familiar environment. Through standardized tasks and associated scorecards, clinicians assess four meaningful domains of functioning: communication, activities of daily living (ADLs, which include fine motor skills), gross motor, and external direction (i.e., the ability to follow directions) via scorecards with pre-established criteria. The aim of this project was to develop and refine the scorecards using a rigorous process in partnership with caregivers, clinicians, and researchers in the AS community.

Eye contact is one of the most important forms of interpersonal communication. Nonetheless, research has shown that there is no gold standard for how eye contact should occur. Atypicalities in eye contact are one of the core features of autism spectrum disorder (ASD), but there is still no consensus on what constitutes atypical eye contact in ASD. The current research explores both the breadth and depth of experiences with eye contact in adults with and without ASD. We used a hermeneutic phenomenological multicenter design in which 15 adults with ASD and 15 adults without ASD were interviewed. Analyses using Multisite Qualitative Analysis (MSQA) and the PRICE model for saturation identified four themes: opinion on eye contact, experience of eye contact, approach toward eye contact, and needs regarding eye contact. Adults with and without ASD appeared to have overlapping and distinct experiences. This study provides the first insights into similarities and differences in experiences with eye contact in adults with and without ASD. The results provide guidance for future research and for the development of interventions to reduce problems arising from eye contact in ASD.

CLN3 disease, also known as juvenile Batten disease, is a recessively inherited neurodevelopmental disorder caused by mutations in the CLN3 gene. It represents the most common form of Neuronal Ceroid Lipofuscinoses (NCLs), a group of lysosomal storage disorders that impair brain function. Clinical features include progressive vision loss, language impairment, and cognitive decline. The early onset of visual deficits complicates the neurological assessment of cognitive dysfunction, while the rarity of CLN3 cases limits the study of sex-specific disease trajectories in humans. Therefore, there is a critical need for objective, translational biomarkers to monitor disease progression and support therapeutic development in preclinical animal models.

This comprehensive review aimed to investigate the transferability of transcranial electrical Stimulation (tES) interventions in individuals with specific learning disabilities (SLD) based on the FIELD model, encompassing function, implements, ecology, level, and durability. A systematic search of electronic databases yielded a total of 13 eligible studies, 11 transcranial direct current stimulation (tDCS), 1 transcranial random noise stimulation (tRNS), and 1 transcranial alternating current stimulation (tACS), encompass 286 individuals with SLD, for inclusion. The overall effect size analysis revealed positive transfer effects in all domains of FIELD, indicating the potential effectiveness of non-invasive brain stimulations (NIBS) interventions in enhancing various aspects of learning and behavior in individuals with SLD. The subgroup analysis further underscored the positive impact of age, dose, and concurrent intervention on transferability. In conclusion, this study contributes valuable insights into the transferability of tES interventions and holds promise for improving learning and behavioral outcomes in individuals with SLD.

Dysregulated endocannabinoid signaling is involved in Fragile X syndrome (FXS), suggesting a potential role for the endocannabinoid signaling modulator, cannabidiol, in treatment. ZYN002 is a synthetic cannabidiol that has been uniquely formulated as a gel for transdermal delivery and is currently under investigation for the treatment of behavioral symptoms associated with FXS.

Exogenous (outward-directed) and endogenous (inward-directed) neural systems are essential for cognition and behavior. However, how they are altered in neurodiverse (ND) children remains unanswered in part due to heterogeneity. Sensory over-responsivity (SOR), the most prevalent form of sensory processing disorder (SPD), serves as a quintessential paradigm for investigating the interaction between exogenous and endogenous brain networks given that both basic and higher-order sensory processing are substantially implicated in this condition.

Importance: The neurodevelopmental outcomes of children born after medically assisted reproduction remain incompletely characterized on a population level. We were to assess the incidence and relative risk of neurodevelopmental delay in the children of infertile women born after unassisted conception, intrauterine insemination (IUI), and in vitro fertilization (IVF).

Rare copy number variants (CNVs) are known to be important contributors to the genetic cause of developmental differences (DD). Parental cognitive phenotyping could assist with interpreting inherited variants of uncertain significance (VUS), and could help to assess phenotypic variability and improve genetic counseling. However, no methodological framework exists for the intergenerational correlation of cognitive abilities. We introduce an approach to assess intrafamilial concordance of cognitive abilities and apply it to three trio cohorts: adults with de novo 22q11.2 microdeletion (n = 50) acting as a high penetrance control for the method, probands with inherited 15q11.2 BP1-BP2 deletions (n = 10) which is associated with a low penetrance of DD, and probands with DD and a rare CNV classified as VUS (CNVUS) and inherited from a parent with seemingly typical development (n = 21).

Pathogenic CASK variants are associated with neurodevelopmental disorders of variable severity including X-linked intellectual disability (XLID) and microcephaly with pontocerebellar hypoplasia (MICPCH). Although the number of diagnosed cases is rising, current understanding of the CASK-related neurodevelopmental spectrum is limited. Here, we systematically review the published characteristics of individuals with CASK-related disorder, and compare these to a more recently-diagnosed group. We provide quantitative information about the ranges of adaptive abilities, motor function, visual function and social-emotional-behavioural characteristics, and explore within-group associations.

This study aims to identify clinical and developmental factors associated with psychotropic medication exposure and subspecialty psychiatric service utilization among patients with genetic neurodevelopmental disorders (GNDDs).

Symptoms of attention-deficit/hyperactivity disorder (ADHD) are common in children with autism spectrum disorder (ASD), and are associated with greater developmental challenges, poorer clinical outcomes, and alterations in functional connectivity (FC) of the brain. However, despite the consensus that ASD and other neurodevelopmental conditions emerge early in life, little is known about the trajectories of brain and behavioral development during the first years of life in children with ASD and co-occurring attention problems (AP).

FOXG1 syndrome is a severe genetic neurodevelopmental disorder characterized by intellectual and developmental disabilities (IDD), postnatal microcephaly, epilepsy, and movement disorder. With the advent of molecular therapies, establishing the natural history of FOXG1 syndrome is critical to enable clinical trial readiness. However, traditional study designs are challenging to implement for rare disorders without significant burden to participants.

Angelman syndrome (AS) is a single-gene neurodevelopmental disorder caused by loss of function of the maternal copy of the gene. Nearly all individuals with AS lack speech, resulting in major impacts on daily life for patients and caregivers. To evaluate new therapies for AS, it is crucial to have a mouse model that characterizes meaningful clinical features. Vocalizations are used in many contexts in mice, including pup retrieval, social interactions, courtship, and distress. Previous work in the mouse model of AS found abnormalities in the number of ultrasonic vocalizations (USVs) mice produced during pup isolation and same-sex social interactions. Here, we evaluated vocalizations during courtship and distress. Quantifying USVs in these contexts enables comparison of USVs in social (courtship) and non-social (distress) settings. In addition, we assessed the utility of incorporating USV testing into existing mouse behavioral assessments used to evaluate potential AS treatments.

NRXN1 deletion (NRXN1 del) is a rare copy number variant associated with several neurodevelopmental, neuropsychiatric, and cognitive outcomes. The NRXN1 gene encodes for a pre-synaptic cell adhesion molecule that is important for synapse formation, regulation and neurotransmission. We used a gene-first approach to investigate neurocognitive and brain phenotypes in NRXN1 del carriers.

There have been increasing numbers of clinical trials of medications for fragile X syndrome (FXS) in recent years, many targeted at proposed underlying cellular or circuit based mechanisms. As yet none of these have led to widespread changes in clinical practice. Genetic therapies represent a different therapeutic approach, which aim to address the genetic mechanisms by which FXS arises. Although not yet moving into human studies in FXS, this is an area of increasing research importance in neurodevelopmental conditions more broadly. It is important that families affected by FXS get the chance to give their views about future genetic therapies, given the potential controversies around genetic therapies.

MED13L-related disorder is associated with intellectual disability, motor delay, and speech deficits. Previous studies have focused on broad clinical descriptions of individuals, but limited information regarding specific speech diagnoses and results of direct testing has been published to date. We conducted deep phenotyping to characterize the speech, language, motor, cognitive, and adaptive phenotypes of individuals with MED13L-related disorder.

To improve the quality of care and the impact of interventions for individuals with (genetic) intellectual disabilities ((G)ID), it is essential to identify and measure relevant patient reported outcomes (PROs), which represent patient perspective on their health and functioning. Currently, various, and potentially irrelevant PROs are being measured for individuals with (G)ID. The aim of this study is to identify relevant PROs from the perspective of different stakeholders, as one of the first steps towards development of a meaningful PRO set for children and adults with (G)ID.

Restricted and repetitive behaviors (RRB) are core features of autism but are also observed in typical development. Our understanding of the neural underpinnings of RRBs is limited. Given that excitation-inhibition (E/I) balance may underlie RRBs, we aimed to evaluate the relationship between aperiodic exponent (as a proxy of E/I balance) and changes in RRBs over time in infants with and without elevated likelihood of autism.

Eukaryotic initiation factor 5 A (eIF5A) and hypusination-related disorders (eIF5A-HRD) are recently described diseases caused by pathogenic heterozygous variants in the translation factor EIF5A or biallelic variants in the two enzymes involved in the post-translational synthesis of hypusine in the eIF5A precursor, deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH), necessary for its activation. We review the current knowledge regarding eIF5A-HRD, and report the case of the sixth and oldest known patient with DOHH-related disorder (DOHH-D), aiming to expand and discuss the molecular basis and the general and epilepsy phenotypes of this group of diseases.

Social perception and attention markers have been identified that, on average, differentiate autistic from non-autistic children. However, little is known about how these markers predict behavior over time at both short and long time intervals.

Estimating time and making predictions is integral to our experience of the world. Given the importance of timing to most behaviors, disruptions in temporal processing and timed performance are reported in a number of neuropsychiatric disorders such as Schizophrenia, Autism Spectrum Disorder (ASD), Fragile X Syndrome (FXS), and Attention-deficit Hyperactivity Disorder (ADHD). Symptoms that implicitly include disruption in timing are atypical turn-taking during social interactions, unusual verbal intonations, poor reading, speech and language skills, inattention, delays in learning, and difficulties making predictions. Currently, there are no viable treatments for these symptoms, the reason being the underlying neural dysfunction that contributes to timing deficits in neuropsychiatric disorders is unknown. To address this unknown, we have designed a novel Temporal Pattern Sensory Discrimination Task (TPSD) for awake-behaving mice. Stimuli consist of paired audiovisual stimuli that differ in duration. Compared to Wild-Type (WT) mice, Fmr1 mice, a well-established mouse model of FXS, showed significant impairment in learning the TPSD task, as evidenced by reduced discriminability indices and atypical licking patterns. Often sensory information is multimodal and, indeed, studies show that learning in humans and rodents improves with multimodal stimuli than with unimodal stimuli. To test how the multimodal nature of stimuli impacted performance of Fmr1 mice, following training on the audiovisual stimuli, we tested mice on audio-only or visual-only stimuli. While WT mice showed significant disruption in performance when tested on unimodal stimuli, Fmr1 mice displayed equivalent performance on visual-only stimuli when compared to the multimodal task. Our novel task captures timing difficulties and multisensory integration issues in Fmr1 mice and provides an assay to examine the associated neural dysfunction.