Explore the vast range of titles available.

•Individuals with Williams Syndrome (WS) show action recognition impairments.•WS shows selective sensitivity to context predictability in action recognition.•Attenuated mu suppression reveals altered action processing in WS. Williams syndrome (WS) is a neurodevelopmental disorder marked by social difficulties, which may stem from atypical action processing. We investigated whether individuals with WS show impaired action processing as indexed by electroencephalographic (EEG) mu suppression, a biomarker of action processing. 17 individuals with WS, 17 healthy controls (HC) and 17 individuals with intellectual and developmental disability (IDD) participated in the study. During EEG recording, participants performed a task requiring to predict actions under perceptual ambiguity. In a preceding learning phase, the probability of actions co-occurring with contextual cues was manipulated to establish varying association strengths: high informativeness from very frequent or rare pairings, and moderate informativeness from intermediate ones. A control task required to use contextual cues for predicting moving shapes. HC and WS groups, but not the IDD group, utilized contextual cues to predict action/shape unfolding. EEG data revealed distinct patterns of mu event-related desynchronization (mu-ERD) across groups. In the HC group, mu-ERD was stronger during action than shape prediction and varied with the cue probability, with greater mu-ERD in low vs. high probability trials. In WS and IDD, mu-ERD was attenuated compared to HC. Notably, WS participants exhibited greater mu-ERD for low- than high-probability actions in moderately informative contexts; no modulation was observed in highly informative contexts in either task. In IDD, mu-ERD was not modulated by task or cues predictability. The attenuation and distinct contextual modulation of mu-ERD in WS may reflect anomalies in perception–action mechanisms, potentially linked to impaired simulation of observed actions.

•Motor and visuospatial functions are predictors of social skills in IDD children.•Deviation from typical development of cortical thickness might impair cognition.•Fronto-parietal areas impact social skills via attention and visuospatial abilities.•Early visuospatial rehabilitation may improve social skills in IDD. Different theoretical perspectives emphasize the significance of sensorimotor and visuospatial functions in shaping social perception, including theory of mind (ToM) and affect recognition (AR) abilities. This study aimed to investigate where in the brain cortical thickness (CT) predicts social perception, and which cognitive functions mediate such relationship. To these aims, we used a hierarchical analytical plan: Step 1 identified brain areas’ CT that correlate with cognitive measures; Step 2 used stepwise regression to predict social perception outcomes (ToM and AR) from brain areas’ CT; Step 3 assessed whether cognitive measures mediate the link between CT and social perception outcomes. The results showed that the CT of the left inferior frontal gyrus (IFG; pars triangularis) predicted both ToM and AR, while the CT of the right superior parietal gyrus (SPL) and of the right anterior occipital sulcus (AOcs) predicted only AR. Mediation models unveiled that visuo-constructive abilities and visual attention mediated the relationship between CT in these areas and social perception outcomes. These findings align with the role of the IFG in mentalizing abilities and underscore the involvement of SPL in visuospatial functions, including mental object rotation and spatial perspective-taking, which are essential for advanced social skills; the role of the AOcs in face processing was also highlighted. Importantly, the findings suggest that fronto-parietal areas are indirectly involved in social perception thorough their involvement in visuo-constructive abilities and visual attention.

Although the uneven neuropsychological profile of William Syndrome (WS) is well established, less is known about social perception and how profile characteristics may affect the ability to predict other’s intentions, a main hallmark of social cognition. This study aimed at examining the neuropsychological profile, including social perception, of adolescents and adults with WS, and at verifying which neuropsychological outcome might account for their social prediction ability. Twenty-six individuals with WS were administered a comprehensive neuropsychological assessment, and a virtual reality scenario designed to assess social prediction in a dynamic, everyday life-like context. We found that social perception was a relative strength of the profile, although a dissociation emerged between impaired verbal ToM and relatively spared low-level components. Peaks and valleys were reported in other domains consistently with the expected profile. Both spatial and facial memory were significantly associated with the performance at the social prediction task. Results clarified that social perception per se should not be considered as typically impaired in WS. Weaknesses and strengths in specific abilities, particularly spatial and facial memory, might affect the ability to understand others’ intentions in WS beyond domain-specific mechanisms. These findings might inform future syndrome-specific rehabilitative interventions.

Background The precise etiology of septo-optic dysplasia (SOD) remains elusive, to date a complex interaction between genetic predisposition and prenatal exposure to environmental factors is believed to come into play. Being SOD such a heterogeneous condition, disruption of many developmental steps in the early forebrain development might occur. The knowledge of genes possibly determining SOD phenotype should be improved, therefore in this review the authors attempt to highlight the genetic pathways and genes related to this clinical condition. Main body Literature search was conducted and updated in November 2023, using PubMed and Google Scholar to identify primary research articles or case reports with available full text using the following search string “case reports,” “humans,” “septo-optic dysplasia,” “optic nerve hypoplasia,” with a recognized genetic diagnosis. Moreover, a review of genetic pathways with an involvement in SOD etiology was conducted. This review thus represents the authors’ perspective based on selected literature. The several pathways presented might be already associated to other disease phenotypes and interplay with genes and pathways known to have a role in SOD determination. Those pathways may converge and thus, the implicated genes may function as cascading regulators at multiple levels. Conclusion The present data suggest that genes other than HESX1, SOX2, SOX3 , and OTX2 might be investigated in candidate individuals with a clinical diagnosis of SOD corresponding to the presence of at least two diagnostic criteria, particularly in the presence of additional syndromic anomalies.

Both acquired injuries and congenital malformations often cause lifelong disabilities in children, with a significant impact on cognitive abilities. Remote computerized cognitive training (CCT) may be delivered in ecological settings to favour rehabilitation continuity. This randomized clinical trial (RCT) evaluated the efficacy of an 8-week multi-domain, home-based CCT in a sample of patients aged 11–16 years with non-progressive acquired brain injury (ABI), brain tumor (BT) and congenital brain malformation (CBM). Following a stepped-wedge research design, patients were randomized into two groups: Training-first group, which started the CCT immediately after baseline assessment and Waiting-first group, which started the CCT after a period of time comparable to that required by the training (8 weeks). Post-training and long-term (6 months) changes were assessed. Both groups improved on visual–spatial working memory after the CCT, with benefits maintained after 6 months, while no other changes in cognitive or psychological measures were found. These findings suggest that a multi-domain CCT can generate benefits in visual–spatial working memory, in accordance with data from extant literature reporting that computer games heavily engage visuo-spatial abilities. We speculate that is tapping on the same cognitive ability with a prolonged training that may generate the greatest change after a CCT.

Pediatric brain damage is associated with various cognitive deficits. Cognitive rehabilitation may prevent and reduce cognitive impairment. In recent years, home-based computerized cognitive training (CCT) has been introduced in clinical practice to increase treatment opportunities for patients (telerehabilitation). However, limited research has been conducted thus far on investigating the effects of remote CCT for the juvenile population in contexts other than English-speaking countries. The aim of the present study was to investigate the feasibility of a home-based CCT in a group of Italian adolescents with brain damage. A commercially available CCT (Lumosity) developed in the English language was used due to the lack of telerehabilitation programs in the Italian language that allow stimulation of multiple cognitive domains and, at the same time, remote automatic collection of data. Thus, this investigation provides information on the possibility of introducing CCT programs available in foreign languages in countries with limited investment in the telerehabilitation field. 32 adolescents aged 11-16 with a diagnosis of congenital or acquired (either traumatic or non-traumatic) brain damage participated in the study. They received 40 training sessions (5 days/week for 8 weeks). Before starting the training program, they received face-to-face demonstration of training exercises and written instructions in their mother tongue. The feasibility of both training and study design and procedures was assessed through 9 criteria taken from extant literature. All 9 feasibility criteria were met. 31 out of the 32 participants demonstrated adherence to the training program. 94.2% of training sessions were completed in the recommended timeframe. No significant technical issue was found. Telerehabilitation seems to be a feasible practice for adolescents with brain damage. A training program developed in a foreign language can be used to counter the unavailability of programs in patients' mother tongue. The trial is registered with the ISRCTN registry with study ID ISRCTN59250807.

Individuals with acquired brain injury (ABI) commonly present with impairments in cognitive abilities. As these competencies seem to be predictive of patients’ abilities to reintegrate into the everyday settings, it is crucial to assess them properly. However, previous research has indicated that patients may perform relatively well on standard tests of cognitive functioning, but may nonetheless encounter significant difficulties in organizing and executing everyday tasks. In order to overcome this issue, virtual reality (VR) methods have been introduced in clinical practice with the aim of creating assessments that simulate real-world activities and thus, provide a clearer picture of patients’ functioning in everyday settings. This review offers an overview of VR assessment tools described in the scientific literature between 2010 and 2019. Overall, 38 relevant records describing 31 different tools were found. Among these tools, 16 assessed executive functions and prospective memory, while the other 15 assessed visuo-spatial abilities. Although promising results have been reported, our analysis indicated that about half of the tools deliver tasks that differ from everyday activities, thus limiting the generalizability of patients’ performance to the real-world. Moreover, a variety of methodological shortfalls related to study Internal and External Validity have been highlighted, which hamper the possibility of drawing definite recommendations on tool choice. These limitations suggest the importance of putting considerable efforts into the improvement or development of VR tools for patients with ABI for both research and clinical purposes, considering the great potential of this form of assessment.

BackgroundDominant and recessive variants in the KIF1A gene on chromosome 2q37.3 are associated with several phenotypes, although only three syndromes are currently listed in the OMIM classification: hereditary sensory and autonomic neuropathy type 2 and spastic paraplegia type 30, both recessively inherited, and mental retardation type 9 with dominant inheritance.MethodsIn this retrospective multicentre study, we describe the clinical, neuroradiological and genetic features of 19 Caucasian patients (aged 3–65 years) harbouring heterozygous KIF1A variants, and extensively review the available literature to improve current classification of KIF1A-related disorders.ResultsPatients were divided into two groups. Group 1 comprised patients with a complex phenotype with prominent pyramidal signs, variably associated in all but one case with additional features (ie, epilepsy, ataxia, peripheral neuropathy, optic nerve atrophy); conversely, patients in group 2 presented an early onset or congenital ataxic phenotype. Fourteen different heterozygous missense variants were detected by next-generation sequencing screening, including three novel variants, most falling within the kinesin motor domain.ConclusionThe present study further enlarges the clinical and mutational spectrum of KIF1A-related disorders by describing a large series of patients with dominantly inherited KIF1A pathogenic variants ranging from pure to complex forms of hereditary spastic paraparesis/paraplegias (HSP) and ataxic phenotypes in a lower proportion of cases. A comprehensive review of the literature indicates that KIF1A screening should be implemented in HSP regardless of its mode of inheritance or presentations as well as in other complex neurodegenerative or neurodevelopmental disorders showing congenital or early onset ataxia.

Purpose Germline WWOX pathogenic variants have been associated with disorder of sex differentiation (DSD), spinocerebellar ataxia (SCA), and WWOX -related epileptic encephalopathy (WOREE syndrome). We review clinical and molecular data on WWOX -related disorders, further describing WOREE syndrome and phenotype/genotype correlations. Methods We report clinical and molecular findings in 20 additional patients from 18 unrelated families with WOREE syndrome and biallelic pathogenic variants in the WWOX gene. Different molecular screening approaches were used (quantitative polymerase chain reaction/multiplex ligation-dependent probe amplification [qPCR/MLPA], array comparative genomic hybridization [array-CGH], Sanger sequencing, epilepsy gene panel, exome sequencing), genome sequencing. Results Two copy-number variations (CNVs) or two single-nucleotide variations (SNVs) were found respectively in four and nine families, with compound heterozygosity for one SNV and one CNV in five families. Eight novel missense pathogenic variants have been described. By aggregating our patients with all cases reported in the literature, 37 patients from 27 families with WOREE syndrome are known. This review suggests WOREE syndrome is a very severe epileptic encephalopathy characterized by absence of language development and acquisition of walking, early-onset drug-resistant seizures, ophthalmological involvement, and a high likelihood of premature death. The most severe clinical presentation seems to be associated with null genotypes. Conclusion Germline pathogenic variants in WWOX are clearly associated with a severe early-onset epileptic encephalopathy. We report here the largest cohort of individuals with WOREE syndrome.

BackgroundPontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorders characterised by concurrent hypoplasia of the pons and the cerebellum and variable clinical and imaging features. The current classification includes 13 subtypes, with ~20 known causative genes. Attempts have been made to delineate the phenotypic spectrum associated to specific PCH genes, yet clinical and neuroradiological features are not consistent across studies, making it difficult to define gene-specific outcomes.MethodsWe performed deep clinical and imaging phenotyping in 56 probands with a neuroradiological diagnosis of PCH, who underwent NGS-based panel sequencing of PCH genes and MLPA for CASK rearrangements. Next, we conducted a phenotype-based unsupervised hierarchical cluster analysis to investigate associations between genes and specific phenotypic clusters.ResultsA genetic diagnosis was obtained in 43 probands (77%). The most common causative gene was CASK, which accounted for nearly half cases (45%) and was mutated in females and occasionally in males. The European founder mutation p.Ala307Ser in TSEN54 and pathogenic variants in EXOSC3 accounted for 18% and 9% of cases, respectively. VLDLR, TOE1 and RARS2 were mutated in single patients. We were able to confirm only few previously reported associations, including jitteriness and clonus with TSEN54 and lower motor neuron signs with EXOSC3. When considering multiple features simultaneously, a clear association with a phenotypic cluster only emerged for EXOSC3.Conclusion CASK represents the major PCH causative gene in Italy. Phenotypic variability associated with the most common genetic causes of PCH is wider than previously thought, with marked overlap between CASK and TSEN54-associated disorders.