Coffin-Lowry syndrome (CLS) is a rare X-linked neurodevelopmental disorder traditionally considered non-progressive. Emerging reports suggest that a subset of individuals may experience developmental regression, although this phenomenon remains poorly characterized in CLS. We conducted a cross-sectional, caregiver-reported survey of individuals with CLS to assess the frequency, clinical features, diagnostic findings, and caregiver-reported treatment responses associated with developmental regression. Descriptive statistics and univariate logistic regression analyses were used to evaluate associations with reported regression. Among caregivers of 93 individuals with CLS, 45.2
Children with Mendelian neurodevelopmental disorders (NDDs) carry genetic variations that increase the risk for a variety of behavioural problems. Behavioural heterogeneity in these conditions often crosses traditional behavioural syndrome classification categories, highlighting the limitations of the use of these categorical classifications for outlining genetic risk. Instead, specific domains of behavioural functioning that are important for daily activities may be of relevance to understand the risk of developmental impact. Coffin-Siris syndrome (CSS), caused by pathogenic variants in chromatin remodeling genes including ARID1B, is increasingly well-characterized genetically, but the impact on behavioural dimensions contributing to its phenotype so far remain unclear. Behavioural functioning was assessed using a multi-instrument approach to capture both broad patterns of emotional and behavioural problems and more specific symptom dimensions related to ADHD and ASD. For general screening of behavioral problems the CBCL (Child Behaviour Checklist) was used. In addition symptoms of ADHD were measured with the SWAN (Strengths and Weaknesses of ADHD Symptoms), and symptoms of ASD with the SRS-2 (Social Responsiveness Scale). Analyses focused on symptom severity relative to normative expectations, the proportion of children exceeding clinical thresholds, age-related variability and associations with severity of intellectual disability. CBCL analyses indicated that children with CSS showed elevated difficulties across multiple domains, with prominent attention problems, atypical or preoccupying thoughts, and social behavioural challenges. Dimensional analyses revealed that, although both inattention and hyperactive-impulsive behaviours were elevated, attentional deficits were more pronounced. Similarly, all ASD-related dimensions were elevated, but social cognition and repetitive behaviours were most prominent, whereas social motivation was relatively preserved. Symptom severity showed no association with age or intellectual disability. These findings suggest that behavioural difficulties in CSS reflect selective elevations across specific behavioural dimensions rather than a behavioural syndrome that is defined by a specific combination of symptoms. A dimensional perspective highlights variability in attention regulation, cognitive processing, and social behaviour, providing a framework to link genetic variation in risk to individual developmental outcomes. Conceptualizing the impact of CSS in behavioral dimensions that may be at risk may provide directions towards targeted and personalized interventions and guide assessment strategies for genetically defined NDDs. Not applicable.
Angelman syndrome (AS) is a rare genetic neurodevelopmental disorder with a characteristic phenotype that includes severe intellectual disability, absent or minimal speech, movement disorder and apparently happy demeanor. The Angelman Syndrome Clinic at the Children’s Hospital of Eastern Ontario is the first specialized clinic of its kind in Canada and was established to provide multidisciplinary care to individuals with AS and their families. This study presents data on a cohort of children and adults who were evaluated in the clinic from its inception in 2016 to 2023. Data were collected prospectively using questionnaires and interviews from parents of participants with a molecularly confirmed diagnosis of Angelman syndrome and were analyzed retrospectively. The investigator-developed, structured parent questionnaire was specifically designed to capture a range of medical, developmental and behavioral concerns that are commonly reported in AS in addition to parents’ need for additional information. A separate satisfaction survey was used to evaluate their experiences with the services received and to solicit suggestions for clinic improvement. Seventy-one children and adults (55
Autism spectrum disorder (ASD) involves disrupted excitatory/inhibitory balance in brain circuits, with interneuron dysfunction implicated across cortical networks. Perisomatic inhibition by parvalbumin-containing (PV) and cholecystokinin-expressing (CCK) basket cells critically regulates principal neuron activity, yet their specific alterations in ASD remain unclear. We investigated cell type-specific changes in perisomatic inhibition within the amygdala using the valproic acid (VPA) mouse model of autism. Pregnant mice received VPA or saline at embryonic day 12.5. Male offspring underwent behavioral testing to assess autistic phenotypes. Following behavioral analysis, immunocytochemical techniques were used to quantify neuronal density, PV-expressing interneuron density, and perisomatic terminal densities of both PV and type 1 cannabinoid receptor (CB1)-expressing CCK basket cells in the lateral and basal amygdala nuclei. Single-cell analysis using Kv2.1 immunostaining quantified perisomatic inputs on individual principal neurons. Optogenetic stimulation combined with patch-clamp recordings validated PV interneuron output changes. Statistical comparisons used Mann-Whitney U tests and two-sample t-tests. VPA-treated mice exhibited autism-like behaviors including reduced ultrasound vocalizations, increased tactile sensitivity, and impaired social interaction and social novelty preferences. Immunocytochemical analysis revealed increased overall neuronal density but decreased PV-expressing interneuron density in the basal amygdala. CB1 + terminal density increased proportionally with neuronal density, while PV+ terminal density failed to compensate, resulting in 16
Evidence suggests that Williams syndrome (WS) may be associated with atypical cortical oscillatory activity and large-scale structural and functional anomalies. However, links between whole-brain electrophysiological measures and cognitive performance in WS remain scarce. This study aimed to characterize classical and novel EEG markers in individuals with WS. We examined spectral power, excitation/inhibition (E/I) balance indexed by the aperiodic exponent, and functional connectivity (i.e., derived brain fluidity, an index of connectivity pattern reconfiguration over time) across canonical frequency bands. Two comparison groups were included: a clinical control group comparable in intelligence quotient (IDD) and a typical development control group comparable in chronological age (TD). Moreover, associations between electrophysiological features and cognitive performance were assessed to clarify the neurophysiological substrates underlying variability in the WS cognitive profile. WS was characterized by distinct electrophysiological alterations in the alpha and beta bands. Alpha and beta power distinguished WS from both control groups, with globally reduced alpha power and reduced parieto-occipital beta power. Additionally, we found reduced individual alpha peak frequency in WS, while no group differences emerged for the aperiodic exponent. Another key finding indicated globally increased fluidity in the alpha band in WS relative to both IDD and TD. Notably, higher fluidity within the WS group was associated with better visuomotor performance, suggesting a compensatory role of fluidity within the WS phenotype. These findings provide a characterization of the electrophysiological profile of WS, revealing selective alterations in rhythmic activity and large-scale network dynamics, while suggesting that network-level measures such as fluidity may offer insights into individual differences in cognitive functioning within the syndrome.
