Search

This pilot study investigates the feasibility and assesses the impact of "Lactobacillus plantarum" PS128 probiotics on the neurological function in Rett syndrome. We conducted a randomized, double-blind, and placebo-controlled trial on Rett syndrome with MECP2 mutation aged between 1 and 50 years in Taiwan. In this pilot study, twice-daily "L. plantarum" PS128 or placebo was administered for 16 weeks. In addition to feasibility, we also assessed the changes utilizing the Mullen Scales of Early Learning. In total, 36 participants were finally randomized into "L. plantarum" PS128 (n = 18) or placebo (n = 18) groups. At the end of intervention, the retention rates were 100% for "L. plantarum" PS128 and 94.44% for placebo, with withdrawal rates of 5.56% for the placebo group. Both groups tolerated well, except for one "L. plantarum" PS128 participant who reported loose stool. The probiotic group showed a change of 2.19 ± 3.76, while the placebo group had -0.85 ± 5.09 (p = 0.051) in the total age-equivalent scores of Mullen Scales of Early Learning. There was a significant difference in the change of the total score on the Burke-Fahn-Marsden Movement Scale between probiotic group and placebo group (-12.19 ± 12.12 vs -4.59 ± 4.20, p = 0.020). In leg dystonia, the probiotic group exhibited a change of -4.11 ± 5.11 compared with -0.38 ± 1.50 in the placebo group (p = 0.008). Our findings affirm the feasibility of "L. plantarum" PS128 in Rett syndrome. Future clinical trials are mandatory to further explore its long-term impact on Rett syndrome.

The present longitudinal study investigated the hypothesis that early musical skills (as measured by melodic and rhythmic perception and memory) predict later literacy development via a mediating effect of phonology. We examined 130 French-speaking children, 31 of whom with a familial risk for developmental dyslexia (DD). Their abilities in the three domains were assessed longitudinally with a comprehensive battery of behavioral tests in kindergarten, first grade, and second grade. Using a structural equation modeling approach, we examined potential longitudinal effects from music to literacy via phonology. We then investigated how familial risk for DD may influence these relationships by testing whether atypical music processing is a risk factor for DD. Results showed that children with a familial risk for DD consistently underperformed children without familial risk in music, phonology, and literacy. A small effect of musical ability on literacy via phonology was observed, but may have been induced by differences in stability across domains over time. Furthermore, early musical skills did not add significant predictive power to later literacy difficulties beyond phonological skills and family risk status. These findings are consistent with the idea that certain key auditory skills are shared between music and speech processing, and between DD and congenital amusia. However, they do not support the notion that music perception and memory skills can serve as a reliable early marker of DD, nor as a valuable target for reading remediation.

Background: Lipid metabolism plays an essential role in nervous system development. Cholesterol deficiency leads to a variety of neurodevelopmental disorders, such as autism spectrum disorder and fragile X syndrome. There have been a lot of efforts to search for biological markers associated with and causal to ADHD, among which lipid is one possible etiological factor that is quite widely studied. We aimed to evaluate the causal relationship between lipids traits, lipid-lowering drugs, and attention deficit hyperactivity disorder (ADHD) outcomes using Mendelian randomization (MR) studies. Methods: We used summary data from genome-wide association studies to explore the causal relationships between circulating lipid related traits and ADHD. Then, quantitative trait loci for the expression of lipid-lowering drug target genes and genetic variants associated with lipid traits were extracted. Summary-data-based MR and inverse-variance-weighted MR (IVWMR) were used to investigate the correlation between the expression of these drug-target genes and ADHD. Results: After rigorous screening, 939 instrumental variables were finally included for univariable mendelian randomization analysis. However, there is no correlation between lipid profile and ADHD risk. Drug target analysis by IVW-MR method observed that APOB-mediated low-density lipoprotein cholesterol was associated with lower ADHD risk (odds ratio [OR] = 0.90, 95% confidence interval [CI] [0.84, 0.97]; p = .007), whereas "LPL"-mediated triglycerides levels were associated with a higher risk of ADHD (OR = 1.13, 95% CI [1.06, 1.21]; p < .001). Conclusion: Our results suggest that "APOB" gene and "LPL" gene may be candidate drug target genes for the treatment of ADHD.

A significant number of individuals with tuberous sclerosis complex (TSC) exhibit language difficulties. Here, we examined the language-related brain morphometry in 59 participants (7 participants with TSC and comorbid autism spectrum disorder (ASD) (TSC + ASD), 13 with TSC but no ASD (TSC-ASD), 10 with ASD-only (ASD), and 29 typically developing (TD) controls). A hemispheric asymmetry was noted in surface area and gray matter volume of several cortical language areas in TD, ASD, and TSC-ASD groups, but not in TSC + ASD group. TSC + ASD group demonstrated increased cortical thickness and curvature values in multiple language regions for both hemispheres, compared to other groups. After controlling for tuber load in the TSC groups, within-group differences stayed the same but the differences between TSC-ASD and TSC + ASD were no longer statistically significant. These preliminary findings suggest that comorbid ASD in TSC as well as tuber load in TSC is associated with changes in the morphometry of language regions. Future studies with larger sample sizes will be needed to confirm these findings.

3q29 deletion syndrome (3q29del) is associated with neuropsychiatric and neurodevelopmental phenotypes. We previously reported that graphomotor weakness is present in up to 78% of individuals with 3q29del. We have now explored nuances of the graphomotor phenotype and its association with other comorbidities in this population. Participants were recruited from the online 3q29 registry (3q29deletion.org) for two days of deep phenotyping. 32 individuals with 3q29del (62.5% male) were evaluated with the Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI) to assess visual-motor integration. Participants were also evaluated with measures of cognitive ability, executive function, adaptive behavior, and school function. Males with 3q29del performed significantly worse than females on the VMI and Motor Coordination subtest. VMI performance was significantly associated with ADHD diagnosis and cognitive ability. Compared to published data from individuals with 22q11.2 deletion syndrome, individuals with 3q29del showed significantly more impairment. The 3q29 deletion is associated with substantial deficits in visual-motor integration, Visual Perception, and Motor Coordination. Our data suggests that 3q29del may qualify as a nonverbal learning disability. Future studies should assess whether individuals with 3q29del would benefit from early interventions, including occupational therapy.

Purpose: The "Fragile X Messenger Ribonucleoprotein-1 (FMR1)" premutation (FXpm) is a genetic variant that is common in the general population and is associated with health symptoms and disease in adulthood. However, poor understanding of the clinical phenotype during childhood has hindered the development of clinical practice guidelines for screening and intervention. Given that social communication difficulties have been widely documented in adults with the FXpm and are linked with reduced psychosocial functioning, the present study aimed to characterize the communication profile of the FXpm during early childhood. Method: Eighteen children with the FXpm who were identified through cascade testing (89%) or screening at birth (11%) were compared to 21 matched typically developing children, aged 2-4 years. Participants completed standardized assessments of language (Mullen Scales of Early Learning) and adaptive communication (Vineland Adaptive Behavior Scales--II). Social communication was rated from seminaturalistic interaction samples using the Brief Observation of Social Communication Change. Results: Children with the FXpm showed delayed social communication development, with the magnitude of group differences highlighting social communication as a feature that distinguishes children with the FXpm from their peers (p = 0.046, [partial eta-squared] = 0.12). The groups did not differ on the standardized language and adaptive communication measures (ps > 0.297, [partial eta-squared]s < 0.03). Conclusions: Early screening and treatment of social communication delays may be key to optimizing outcomes for children with the FXpm. Further research is needed to replicate findings in a larger sample, delineate the trajectory and consequences of social communication difficulties across the life span in the FXpm, and determine the potential epidemiological significance of "FMR1" as a mediator of developmental communication differences within the general population.

Few studies have examined differences in autism spectrum disorder (ASD) phenotype between children from multiplex and simplex families at the time of diagnosis. The present study used an age- and gender-matched, community-based sample (n = 105) from the southwestern United States to examine differences in ASD symptom severity, cognitive development, and adaptive functioning. No significant differences between children from multiplex and simplex families were observed. Exploratory analysis revealed that parents underreported receptive and expressive language and fine motor skills compared to professional observation, especially among children from multiplex families. These findings suggest that diagnosticians may need to consider family structure when choosing and interpreting assessments of receptive language, expressive language, and fine motor skills.

Background: Children with Prader-Willi Syndrome (PWS) display impaired pretend play abilities, reflective of broader social-cognitive challenges. Pretend play interventions for children with PWS demonstrate preliminary efficacy for improving cognitive and affective processes in play. It is unknown which specific intervention strategies, such as prompting, summarization, and modeling, most effectively improve these skills. The present study examined the effectiveness of different interventionist strategies on eliciting child behaviors within pretend play intervention sessions. Methods: Participants included 21 children (ages 6-12) with PWS who participated in a pretend play intervention. Recorded intervention sessions were coded for interventionist strategies and child pretend play skills. By pairing each interventionist strategy with the immediately following child behavior, it was possible to discern the frequency of how often certain intervention strategies immediately preceded various child pretend play skills. Results: All intervention strategies were followed by child pretend play over 50% of the time. Interventionist summarizing/reflection and modeling most often preceded child pretend play, as well as specific skills of imagination and organization. Prompting, followed by modeling, most often preceded affect expression. Conclusions: Interventionist strategies of summarization and modeling may most effectively facilitate pretend play. Prompts for emotions may be more effective to elicit affect expression, potentially due to social-cognitive difficulties inherent in PWS. Children with developmental differences may benefit from adults who engage in play as a partner, rather than direct the play, to help the child stay on-task and learn target behaviors. This insight may strengthen future efforts to support socioemotional skills through pretend play.

The emerging field of genomic medicine offers an opportunity for biology and anatomy teachers to bring the topics of DNA, genetics, molecular processes, and evolution together into one experience. Through the genomic medicine paradigm, students see the unbroken connection between small biological topics such as mutations and their potential connection to disease phenotypes. In this paper, we present as a main example cystic fibrosis, which is an often-studied genetic disease in general biology class, for examination through the genomic medicine lens. Concepts such as genes, the plasma membrane, variation, mutations, the nucleus, and chromosomes can be used in a narrative and visual approach to genetics through the genomic medicine standpoint to engage and connect students with next-generation genomics and with the fundamental unit of life -- the cell. It is through the genomic medicine lens that the cell's context and relationship to the evolving world takes place.

Atypical habituation to repetitive information has been commonly reported in Autism Spectrum Disorder (ASD) but it is not yet clear whether similar abnormalities are present in Neurofibromatosis Type 1 (NF1). We employed a cross-syndrome design using a novel eye tracking paradigm to measure habituation in preschoolers with NF1, children with idiopathic ASD and typically developing (TD) children. Eye movements were recorded to examine fixation duration to simultaneously presented repeating and novel stimuli. Children with NF1 showed a bias for longer look durations to repeating stimuli at the expense of novel stimuli, and slower habituation in NF1 was associated with elevated ASD traits. These findings could indicate aberrant modulation of bottom-up attentional networks that interact with the emergence of ASD phenotypes.

Background: The Fragile X community has expressed a desire for centralised, national guidelines in the form of integrated guidance for Fragile X Syndrome (FXS). Methods: This article draws on existing literature reviews, primary research and clinical trials on FXS, a Fragile X Society conference workshop and first-hand experience of clinicians who have worked with those living with FXS over many years. Results: The article scopes proposed integrated guidance over the life course, including appendices of symptoms, comorbidities and referral options for FXS and Fragile X Premutation Associated Conditions. Conclusion: Integrated guidance would provide an authoritative source for doctors, health professionals, therapists, care workers, social workers, educators, employers, families and those living with FXS, so that a holistic, person-centred approach can be taken across the United Kingdom to garner the best outcomes for those with FXS.

This paper discusses language use and identity patterns in ethnic minority/ethnically heterogeneous multigenerational deaf families in Romania, where at least one of the family members belongs to the ethnic Hungarian minority. Early childhood and school linguistic socialization, language use within the family, and cross-generational transmission of identity to children are explored. The research is based on five ethnic minority/ethnically heterogeneous multigenerational deaf family case studies. The research results show that within ethnic-national minority/ethnically heterogeneous multigenerational deaf families, complex identity patterns may develop and multifaceted linguistic communication models may prevail, including the use of national oral languages and national sign languages of the parties involved. At the same time, a kind of special linguistic and cultural enrichment, a striving for cultural-linguistic balance, may occur.

Objective: There is growing evidence of involvement of inflammatory mechanisms in ADHD. Previous studies found significantly higher rates of ADHD among children with FMF. The present study examined the rate of exposure to FMF in children with a later (within a 5-year period) diagnosis of ADHD compared to non-ADHD children. Methods: A population-based case-control study of all children (<18 years) registered in Leumit Health Services during 01.01.2006 to 06.30.2021. All cases met ICD-9/10 criteria for ADHD. They were matched by age, sex, and socioeconomic status on a 1:2 rate to randomly selected non-ADHD controls. Results: Fifty-six (0.30%) children with ADHD (N = 18,756) were previously diagnosed with FMF compared to 65 of 37,512 controls (0.17%). A significant, independent association existed between a preceding FMF diagnosis and a later ADHD diagnosis [OR = 1.72 (95% CI 1.18-2.51); p = 0.003]. Conclusions: The mechanisms underlying the association w between FMF and later ADHD diagnosis merit further elucidation.

Objective: To use a family genetic study to evaluate familial risk of obsessive compulsive disorder (OCD) and common comorbid illnesses in first-degree relatives of pediatric-onset probands with primary OCD. Method: One hundred and thirty youth with OCD and their 133 siblings and 241 parents and 49 pediatric controls were directly evaluated along multiple domains including psychopathology using structured diagnostic interviews and clinical corroboration. Results: Rates of anxiety, mood, disruptive behavior, and tic disorders were markedly elevated in the probands while rates in siblings were elevated at rates between the probands and controls. Twenty six percent of first-degree relatives had clinical OCD, 9% had chronic tics or Tourette's disorder, and 21% met criteria for ADHD. Conclusion: Rates of familial transmission of OCD and common comorbid illnesses were significantly higher in our pediatric-onset probands than rates reported in the literature in relatives of those with adult-onset OCD.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition. Genetic, environmental, and epigenetic variables are all likely to have a role in the occurrence of ASD. This systematic review was done to determine the implications of genetic factors and modifiers in ASD. Our results show that nearly all human chromosomes have one or more genes susceptible to autism including X and Y chromosomes. In majority of the studies, different genes like MTHFR, A1298C, KDM5B, AIM2, AMPD1-NRAS, TRIM33, and TRIM33-BCAS2 located on chromosome number 1 were found to have high association with ASD. It is concluded that genes on approximately all human chromosomes have association with the risk of ASD. Given the possible involvement of epigenetic processes in the development of autism and the ability of environmental variables to change gene expression, it seems essential to investigate a variety of factors, particularly interaction between gene and environment.

Although the last decade has welcomed evidence that individuals with Rett syndrome (RTT) can communicate using alternative and augmentative communication (AAC), less is known about effective procedures for teaching various component skills required for expressive communication of individuals with complex communication needs. The purpose of the current study was to evaluate the effects of systematic individualized instruction procedures on the page-linking skills of individuals with RTT. A nonconcurrent multiple baseline design across participants was used to evaluate independent and accurate responding utilizing both a high-tech and low-tech AAC device for three participants. All sessions were conducted in the participants' homes by their parents with remote coaching from a researcher via telehealth. Results indicated that for all three participants, individualized procedures that included behavior chaining, differential reinforcement, and delayed prompting were effective for teaching page-linking in both a high-tech and a low-tech AAC device. Directions for future research and practice are discussed.

The vast majority of individuals with Rett syndrome do not utilize natural speech and therefore require alternative and augmentative communication (AAC). The purpose of the current study was to investigate the use of high- and low-tech AAC modalities by three individuals with Rett syndrome given similar instruction for using both modalities. For all participants, the number of sessions to criterion and cumulative number of trials with independent requests during simultaneous or alternating instruction in the use of a high- and low-tech AAC modality were investigated. Parents conducted all sessions with remote coaching from a research assistant via telecommunication. Each participant exhibited idiosyncratic response patterns in terms of use of their high- and low-tech AAC modalities during instruction but ultimately demonstrated the ability to use both modalities to make requests. Implications for future research and practice pertaining to AAC of individuals with complex communication needs are discussed. This paper is a companion to Girtler et al. (2023).

Etiological beliefs of depression have differing impacts on motivation, hope, and treatment expectations. However, it is unclear where people are exposed to these beliefs. Objective: This study examined beliefs about depression and their relations to symptoms, attitudes about depression, and treatment preferences. Participants: 426 undergraduates attending a large midwestern university. Methods: Participants completed an online survey asking about causes of depression, if and where they had heard about the "chemical imbalance" explanation of depression, attitudes about depression, as well as measures of their symptoms, treatment history, and hypothetical treatment preferences. Results: Sixty-two percent of the sample had heard of the chemical imbalance explanation, most commonly from the classroom. Biochemical beliefs about depression were most strongly endorsed among participants with a family history of depression and who had had personal experience with treatment. The chemical imbalance belief was uniquely related to dysfunctional beliefs about depression. Etiological beliefs were largely unrelated to treatment preferences. Conclusion: College students are exposed to models of mental health that may not be ideal for treatment and recovery.

The ability to connect key concepts of biochemistry with clinical presentations is essential for the development of clinical reasoning skills and adaptive expertise in medical trainees. To support the integration of foundational and clinical sciences in our undergraduate health science curricula, we developed a small group active learning exercise during which interprofessional groups of students use clinical cases to explore the biochemistry, diagnostic strategy, and evidence-based treatment options of inborn errors of metabolism (IEM). We designed multistage learning modules consisting of (1.) low-fidelity case simulations of pediatric patients presenting with IEMs, (2.) guided group discussions on clinical biochemistry, differential diagnoses, and diagnostic strategies, (3.) oral presentations of clinical reasoning strategies, and (4.) discussion of relevant evidence-based medicine topics related to the cases. These modules Scientific Knowledge Integrated in Patient Presentations (SKIPPs) were added to a first-semester foundational sciences course serving five health professions programs. The assessment of learning outcomes by students and faculty shows that SKIPPs sessions are well-received activities that significantly improve trainees' ability to integrate foundational science concepts into clinical scenarios, to practice interprofessional teamwork and to develop clinical reasoning skills.

The racialized history of sickle cell disease (SCD) continues to contribute to racial disparities in healthcare and education. In the context of the racialized history of SCD, we begin by outlining subtypes of SCD and explaining that SCD is associated with chronic pain, silent cerebral infarct, overt stroke, and poor overall well-being--all of which have implications for school functioning. A literature search was conducted to identify significant meta-analyses, systematic reviews, and empirical articles to inform school psychologists' evaluation, service delivery, and decision-making practices when working with students with SCD. Common negative neuropsychological and psychoeducational outcomes associated with SCD are reviewed. Finally, recommended culturally responsive practices are discussed, ahead of a conclusion that contains a call to action for school psychologists.

To investigate additive and interactive associations of food allergies with three glutathione S-transferase (GST) genes in relation to ASD and ASD severity in Jamaican children. Using data from 344 1:1 age- and sex-matched ASD cases and typically developing controls, we assessed additive and interactive associations of food allergies with polymorphisms in GST genes (GSTM1, GSTP1 and GSTT1) in relation to ASD by applying conditional logistic regression models, and in relation to ASD severity in ASD cases as measured by the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2) total and domains specific comparison scores (CSs) by fitting general linear models. Although food allergies and GST genes were not associated with ASD, ASD cases allergic to non-dairy food had higher mean ADOS-2 Restricted and Repetitive Behaviors (RRB) CS (8.8 vs. 8.0, P = 0.04). In addition, allergy to dairy was associated with higher mean RRB CS only among ASD cases with GSTT1 DD genotype (9.9 vs. 7.8, P < 0.01, interaction P = 0.01), and GSTP1 Val/Val genotype under a recessive genetic model (9.8 vs. 7.8, P = 0.02, interaction P = 0.06). Our findings are consistent with the role for GST genes in ASD and food allergies, though require replication in other populations.

Fragile X syndrome (FXS) is characterized by variable neurobehavioral abnormalities, which leads to difficulties in developing and evaluating treatments and in determining accurate prognosis. We employed a pediatric cross-sectional sample (1,072 males, 338 females) from FORWARD, a clinic-based natural history study, to identify behavioral subtypes by latent class analysis. Input included co-occurring behavioral conditions, sleep and sensory problems, autistic behavior scales (SCQ, SRS-2), and the Aberrant Behavior Checklist revised for FXS (ABC[subscript FX]). A 5-class solution yielded the most clinically meaningful, pharmacotherapy independent behavioral groups with distinctive SCQ, SRS-2, and ABC[subscript FX] profiles, and adequate non-overlap ([greater than or equal to] 71%): "Mild" (31%), "Moderate without Social Impairment" (32%), "Moderate with Social Impairment" (7%), "Moderate with Disruptive Behavior" (20%), and "Severe" (9%). Our findings support FXS subtyping, for improving clinical management and therapeutic development. [Written with the FORWARD Consortium.]

Background: Siblings of children with intellectual disability have unique family experiences, varying by type of disability. Methods: Parents of children with Down syndrome (156) or with Rett syndrome (149) completed questionnaires relating to sibling advantages and disadvantages, experiences of holidays and recreation, and perceived availability of parental time. Qualitative responses were analysed using thematic analysis. Results: Positive personality traits, an optimistic outlook, enhanced skills, and rich relationships were strong and consistent parental perceptions for siblings in both disability groups. Parents of children with Rett syndrome were more likely to rank themselves lower on time availability, and to report sibling difficulties with social engagement and family holidays. Conclusions: Parental responses appeared to be influenced by disability type, and reflective of child capabilities. Perceptions of sibling experience should be supplemented by data collected directly from siblings to fully understand their unique perspective, and the ways in which their experiences could be enhanced.

"ATRX" mutations are commonly associated with alpha-thalassaemia mental retardation syndrome (ATR-X syndrome) with a notable variable expressivity. This X-linked disorder is characterized by intellectual disability (ID) in a higher or lesser degree, in which the alpha-thalassaemia feature is not always present. Other phenotypic manifestations like facial dimorphism, hypotonia, microcephaly, skeletal abnormalities or urogenital malformations have been frequently observed in ATR-X syndrome. Herein, we report a missense ATRX mutation (Thr1621Met) in a patient with an autism spectrum disorder (ASD) diagnosis. Except for ID, no typical signs of ATR-X syndrome were found in the patient. These results confirm the extensive phenotypic variability associated to "ATRX" mutations and show the involvement of this gene in the ASD.

Williams syndrome (WS) is a rare genetic syndrome. As with all rare syndromes, obtaining adequately powered sample sizes is a challenge. Here we present legacy data from seven UK labs, enabling the characterisation of cross-sectional and longitudinal developmental trajectories of verbal and non-verbal development in the largest sample of individuals with WS to-date. In Study 1, we report cross-sectional data between N = 102 and N = 209 children and adults with WS on measures of verbal and non-verbal ability. In Study 2, we report longitudinal data from N = 17 to N = 54 children and adults with WS who had been tested on at least three timepoints on these measures. Data support the WS characteristic cognitive profile of stronger verbal than non-verbal ability, and shallow developmental progression for both domains. Both cross-sectional and longitudinal data demonstrate steeper rates of development in the child participants than the adolescent and adults in our sample. Cross-sectional data indicate steeper development in verbal than non-verbal ability, and that individual differences in the discrepancy between verbal and non-verbal ability are largely accounted for by level of intellectual functioning. A diverging developmental discrepancy between verbal and non-verbal ability, whilst marginal, is not mirrored statistically in the longitudinal data. Cross-sectional and longitudinal data are discussed with reference to validating cross-sectional developmental patterns using longitudinal data and the importance of individual differences in understanding developmental progression.

This study aimed to develop and validate machine learning models to predict intensities in children and adolescents with cystic fibrosis (CF) across different accelerometry brands and placements. Thirty-five children and adolescents with CF (11.6 ± 2.8 yrs; 15 girls) and 28 healthy youth (12.2 ± 2.7 yrs; 16 girls) performed six activities whilst wearing GENEActivs (both wrists) and ActiGraphs GT9X (both wrists and waist). Three supervised learning classifiers (K-Nearest Neighbour, Random Forest and eXtreme Gradient Boosted Decision Tree) were used to identify the input signal pattern for each PA type and intensity, with a 10-fold cross-validation utilized to assess the performance of the classifiers. ActiGraph GT9X on the dominant wrist and waist and GENEActiv on the dominant wrist failed to predict vigorous intensity PA activities. All other models, for activity type and intensities, exceeded 97% accuracy, with a sensitivity and specificity of greater than 95%, irrespective of accelerometer brand, placement or health condition. [This paper was written on behalf of ActiveYouth SRC group.]

Microcephaly presents heterogeneous genetic etiology linked to several neurodevelopmental disorders (NDD). Copy number variants (CNVs) are a causal mechanism of microcephaly whose investigation is a crucial step for unraveling its molecular basis. Our purpose was to investigate the burden of rare CNVs in microcephalic individuals and to review genes and CNV syndromes associated with microcephaly. We performed chromosomal microarray analysis (CMA) in 185 Brazilian patients with microcephaly and evaluated microcephalic patients carrying < 200 kb CNVs documented in the DECIPHER database. Additionally, we reviewed known genes and CNV syndromes causally linked to microcephaly through the PubMed, OMIM, DECIPHER, and ClinGen databases. Rare clinically relevant CNVs were detected in 39 out of the 185 Brazilian patients investigated by CMA (21%). In 31 among the 60 DECIPHER patients carrying < 200 kb CNVs, at least one known microcephaly gene was observed. Overall, four gene sets implicated in microcephaly were disclosed: known microcephaly genes; genes with supporting evidence of association with microcephaly; known macrocephaly genes; and novel candidates, including OTUD7A, BBC3, CNTN6, and NAA15. In the review, we compiled 957 known microcephaly genes and 58 genomic CNV loci, comprising 13 duplications and 50 deletions, which have already been associated with clinical findings including microcephaly. We reviewed genes and CNV syndromes previously associated with microcephaly, reinforced the high CMA diagnostic yield for this condition, pinpointed novel candidate loci linked to microcephaly deserving further evaluation, and provided a useful resource for future research on the field of neurodevelopment.

Sensory differences are nearly universal in autism, but their genetic origins are poorly understood. Here, we tested how individuals with an autism-linked genotype, 16p.11.2 deletion ("16p"), attend to visual information in immersive, real-world photospheres. We monitored participants' (N = 44) gaze while they actively explored 360° scenes via headmounted virtual reality. We modeled the visually salient and semantically meaningful information in scenes and quantified the relative bottom-up vs. top-down influences on attentional deployment. We found, when compared to typically developed control (TD) participants, 16p participants' attention was less dominantly predicted by semantically meaningful scene regions, relative to visually salient regions. These results suggest that a reduction in top-down relative to bottom-up attention characterizes how individuals with 16p.11.2 deletions engage with naturalistic visual environments.

Loss of social supports and community programs due to lockdowns and other measures associated with COVID-19 has been linked to concerns over mental health and feelings of isolation. These challenges can be particularly acute for the elderly and people living with chronic or pervasive health conditions. "Dance for PD," a program specifically developed for people living with Parkinson's Disease, formerly offered in hundreds of locations around the globe, either halted or shifted to a virtual format. Our study investigates the transition of these dance-based programs to an online environment, with the aim of determining the extent to which a virtual format provides affective support or other benefits. Given the increased incidence of mental health problems and social isolation associated with COVID-19, this investigation aims to contribute to the development of better supports for vulnerable populations while helping us understand the specific contributions of dance-based programs in a virtual environment.

Individuals with fragile X syndrome (FXS) and their parents have a range of experiences navigating the crucial transition period between adolescence and adulthood. Semi structured interviews of 47 mothers of adolescents with FXS (mean child age = 15.89 years) were analyzed to identify mothers' changing expectations during the adolescent period and parent goals related to work and postsecondary education. Mothers' work and education goals were explored in relation to child factors such as language skills and autism characteristics. Lower language skills were associated with lower likelihood of reporting vocational goals. Results suggest that adolescents with FXS with lower language ability are less likely to have vocational plans for adulthood during this critical period and may need greater transition planning assistance.

Purpose: Language studies on populations with rare genetic disorders are limited. Hence, there is little data on commonly found or expected developmental linguistic traits and cognitive mechanisms that may be impaired. Based on the hypothesis that there is a close connection between language and cognition and the relevance of specific genetic changes in the development of each, our goal was to provide linguistic data on relationships with other executive functioning mechanisms. Method: This study assessed language skills, communicative behaviors, and executive functions in four children, aged 7-9 years, with rare genetic disorders, using standardized protocols and tests. Results: The findings revealed different levels of language impairment and executive functioning problems in each case. The overall executive function index performance for each of the four cases studied was clinically significantly high, indicating executive dysfunction. Conclusions: The cases analyzed illustrate different types of atypical development that affect both language and other cognitive mechanisms and underscore the importance of executive skills and the various ways in which they are involved in diverse levels of language that might be affected to a greater or lesser degree in rare genetic disorders. In conclusion, we found that language dysfunction is a salient feature of the rare genetic disorders included in our study, although this is not necessarily true for all genetic disorders. Along with these conclusive results, we performed a qualitative analysis of the linguistic and cognitive components that enable functional communication in order to allow optimal interpretation of the data we have collected, laying the foundations for a more effective therapeutic approach.

Speech problems affect about 66% of children with classic galactosemia (CG), but limited evidence is reported on early motor and sensory motor development in this at-risk population. Research has been focused on speech and language development, leaving a paucity of data on motor and sensory differences. This paper describes preliminary data regarding sensory motor and motor development patterns in young children with CG. Babble Boot Camp© (BBC) is an NIH-funded randomized control trial (RCT) implementing proactive interventions designed to support the speech language development of infants with CG. Cases were randomly assigned to a motor-first group (Motor Milestones), receiving virtual occupational therapy through 14 months, or a speech-first group, receiving virtual speech therapy through 14 months. All cases received speech and language therapy from 15 to 24 months. Controls, typically developing infants, did not receive occupational therapy or speech therapy. Participants were recruited through social media, advertisements, metabolic clinics, and the Galactosemia Foundation. Infants in the motor milestones group were assessed with the Developmental Assessment of Young Children and Sensory Profile-2 pre-enrollment (<6 months of age) and post-treatment follow-up at 2.5, 3.5, and 4.5 years of age. Results show that 17.5% of participants with CG had delays in gross motor, 22.5% in fine motor, and 45% in sensory processing. Data from the Motor Milestones portion of BBC are important emerging evidence for occupational therapy in early intervention, preschool, and outpatient settings. This research supports the need for occupational therapy services during early intervention to minimize or prevent long-term motor and sensorimotor delays in infants with CG. Understanding patterns and addressing literature gaps helps support the need for occupational therapists to address motor delays, improve activities of daily living, play, promote functional independence, and provide caregiver education to best support the occupational performance of children with CG.

Purpose: Past research shows that parentally responsive behavior toward the child positively influences language development in both neurotypical children and children with intellectual and developmental disabilities, including those with fragile X syndrome (FXS); however, most studies have focused exclusively on the mother--child relationship. The current study examined relationships between parent behavior (i.e., responsivity and behavior management) and child language performance in both mother-child and father-child interactions, as well as relationships between child characteristics and both parent behavior and child language. Method: Participants were 23 families of young boys with FXS between 3 and 7 years of age. Mothers and fathers independently completed questionnaires assessing child characteristics and separately engaged in 12-min play-based interactions with their child via telehealth. One parent also completed a comprehensive interview assessing child adaptive behavior. Video recordings of the parent--child interactions were transcribed and coded for parent and child behavior, and measures of parent and child language were obtained from the transcripts. Results: Mothers and fathers used similar rates of responsive behaviors during parent-child interactions, and parental responsivity was positively associated with some aspects of child language performance (i.e., talkativeness and lexical diversity). Parental behavior, however, was not associated with syntactic complexity. Older children and children with higher levels of adaptive behavior had parents who used higher rates of responsive behaviors. Fathers used higher rates of behavior management strategies compared to mothers, and this type of parent behavior was not associated with child language. Conclusion: Overall, this study provides evidence that interventions focused on increasing parental responsiveness would be beneficial for families of children with FXS and that these interventions should be delivered early given the association between responsivity and child age.

Purpose: Smith-Magenis syndrome (SMS), a rare, genetically linked complex developmental disorder caused by a deletion or mutation within chromosome 17p11.2, is associated with delays in speech-language development, otopathology, and hearing loss, yet previous studies lack comprehensive descriptions of hearing and communication profiles. Here, analyses of patient registry data expand what is known about speech, language, hearing, and otopathology in SMS. Method: International speech-language and hearing registry survey data for 82 individuals with SMS were analyzed using descriptive and inferential statistics. Hearing loss, history of otitis media and pressure equalization (PE) tubes, communication mode, expressive/receptive language, and vocal quality were analyzed for all subjects and subjects grouped by age. Statistical methods included descriptive statistics and Pearson's chi-square tests of independence to test for differences between age groups for each variable of interest. Association analyses included Pearson's correlations. Results: Hearing and otological analyses revealed that 35% of subjects had hearing loss, 66% had a history of otitis media, and 62% had received PE tubes. Speech-language analyses revealed that 60% of subjects communicated using speech, 79% began speaking words at/after 24 months of age, 92% combined words at/after 36 months, and 41% used sign language before speech. There was a significant association between the age that first words were spoken and the age that PE tubes were first placed. Communication strengths noted in more than 40% of subjects included social interest, humor, and memory for people, past events, and/or facts. Conclusions: Significant delays and impairment in speech-language were common, but the majority of those with SMS communicated using speech by age 6 years. Age was a significant factor for some aspects of hearing loss and communication. Neither hearing loss nor otitis media exacerbated language impairment. These results confirm and extend previous findings about the nature of speech, language, hearing, and otopathology in those with SMS.

The current study examines the efficacy of an 8-week pretend play intervention targeting social-cognitive abilities in children with Prader-Willi syndrome (PWS), ages 6-9. PWS is a rare disorder associated with various social, emotional, and cognitive challenges linked to pretend play impairments, and for which interventions are sparse. Nineteen children were quasi-randomized to receive the intervention or be part of a waitlist control group. Participants who received the intervention (n = 10) demonstrated significant improvements in various components of pretend play, most notably in organization of play, which may generalize to broader social-cognitive gains. These findings provide evidence of the intervention's efficacy in enhancing pretend play skills and related social-cognitive abilities during this critical period of development for children with PWS.

Rett syndrome is a severe neurodevelopmental disorder that results in both motor and language skill regression with a wide range of severity in symptom presentation. Communication intervention may be particularly challenging for this population due to the decline in speech, motor skills, and motor planning difficulties that characterize the disorder (Townend et al., 2020), often resulting in the need for augmentative and alternative communication (AAC) technology. Very limited research has evaluated communication interventions for individuals with Rett syndrome and even fewer have targeted expressive communication, an important skill required for improved autonomy and quality of life (Sigafoos et al., 2009; Townend et al., 2020). The current study sought to systematically replicate the Simacek et al. (2017) mand training procedures to teach three girls with Rett Syndrome to use AAC to make requests through caregiver coaching by researchers via telehealth. Results suggest that mand training was successful in increasing AAC use for all three participants. Barriers to intervention for this population and implications of results for future research and clinical practice are discussed.

Individuals with autism spectrum disorder present with difficulties in social communication, restricted interests or behaviors and other co-morbidities. About 2 to 10% of cases of autism have a genetic cause, and Fragile X Syndrome (FXS) is reported in 0 to 6.5% of individuals with autism. However, the FXS and premutation prevalence among Filipino children has never been reported. The aim of the study was to establish the presence of FXS or premutation carriers among Filipino children with autism and to describe the phenotypic characteristic of cases identified. Blood was collected from 235 children aged 2-6 years old and diagnosed with autism. Samples were analyzed using PCR methods to amplify CGG repeats in the FMRI gene. The diagnosis of autism was confirmed through the Autism Diagnostic Observation Schedule-2. Additional characteristics were documented from a physical examination, Griffiths Scales of Child Development assessment and a parent-answered questionnaire using the Vineland Adaptive Behavior Scale. Fragile X testing through PCR methods in 235 children with diagnosed autism showed 220 (93.6%) were negative, no full mutations, 1 (0.436%) premutation carrier and 14 (5.95%) cases contained intermediate alleles. The FXS testing was limited to confirmed cases of autism, which is considered a high-risk group and does not provide prevalence for the general Filipino population. Subjects were self-referred or referred by clinicians, which may not represent the Filipino autism population with a bias towards those with means for clinical consultations and ability to travel to the place of testing. Samples were not measured for mosaicism, DNA methylation or AGG interspersion patterns. These may have effects on the CGG repeat expansion and overall presentation of FXS. Findings from a single premutation carrier cannot characterize features distinctly present in Filipinos with the mutation. Nevertheless, these results support the data that the prevalence of FXS in Asian populations may be lower than non-Asian populations. This can contribute to a better understanding of FXS and genetic causes of autism in the Philippines and other Asian populations.

Aided augmentative and alternative communication (AAC) modeling is an important approach to facilitating language learning for individuals with complex communication repertoires. This study examines the implementation of this approach during COVID-19 virtual schooling. Key implementation challenges are identified, along with implications for educational practice to facilitate language learning. We conducted a qualitative case study of a 5-year-old child with Rett syndrome, a rare neurological disorder, who used an eye-tracking AAC device. We collected and triangulated data using participant observation of three one-on-one story reading sessions involving the child, her caregiver, and her teacher during virtual schooling as well as a semi-structured interview with the teacher. The study identified key steps for successful language modeling during virtual sessions. These included: ensuring access to the device, promoting attention through gestural and verbal prompts, providing modeling of AAC symbols, confirming responses, providing feedback, using visual supports, a collaborative approach, and positive reinforcement. Our findings suggest these strategies can help facilitate effective language development for children using AAC devices in online schooling contexts. The virtual context presented significant barriers to the practice of aided AAC modeling. Active participation of caregivers and teacher-caregiver collaboration is essential for effective implementation of aided AAC modeling during such schooling.

Problem Addressed: To better understand the factors associated with family cancer history (FCH) information and cancer information seeking, we model the process an individual undergoes when assessing whether to gather FCH and seek cancer information and compare models by sociodemographics and family history of cancer. We used cross-sectional data from the Health Information National Trends Survey (HINTS 5, Cycle 2) and variables (e.g., emotion and self-efficacy) associated with the Theory of Motivated Information Management to assess the process of FCH gathering and information seeking. We completed path analysis to assess the process of FCH gathering and stratified path models. Results: Those who felt they could lower their chances of getting cancer (emotion) were more confident in their ability to complete FCH on a medical form (self-efficacy; B = 0.11, p < 0.0001) and more likely to have discussed FCH with family members (B = 0.07, p < 0.0001). Those who were more confident in their ability to complete a summary of their family history on a medical form were more likely to have discussed FCH with family members (B = 0.34, p < 0.0001) and seek other health information (B = 0.24, p < 0.0001). Stratified models showed differences in this process by age, race/ ethnicity, and family history of cancer. Implications for Public Health Research and Practice: Tailoring outreach and education strategies to address differences in perceived ability to lower chances of getting cancer (emotion) and confidence in the ability to complete FCH (self-efficacy) could help encourage less engaged individuals to learn about their FCH and gather cancer information.

Children with chromosome 22q11.2 deletion syndrome (22q11.2DS) exhibit impaired ability to process and understand emotions in others. We measured structural connectivity in children and adolescents with 22q11.2DS (n = 28) and healthy controls (n = 29). Compared to controls, those with 22q11.2DS had poorer social skills and more difficulty recognizing facial emotions. Children with 22q11.2DS also had higher fractional anisotropic diffusion in right amygdala to fusiform gyrus white matter pathways. Right amygdala to fusiform gyrus fractional anisotropy values partially mediated the relationship between 22q11.2DS and social skills, as well as the relationship between 22q11.2DS and emotion recognition accuracy. These findings provide insight into the neural origins of social skills deficits seen in 22q11.2DS and may serve as a biomarker for risk of future psychiatric problems.

We examined the cognitive, language, and instructional predictors of early word-reading ability in a sample of children with Williams syndrome longitudinally. At Time 1, sixty-nine 6-7-year-olds (mean age = 6.53 years) completed standardized measures of phonological awareness, visual-spatial perception, vocabulary, and overall intellectual ability. Word-reading instruction type was classified as (systematic) Phonics (n = 35) or Other (n = 34). At Time 2, approximately 3 years later (mean age = 9.47 years), children completed a standardized assessment of single-word reading ability. Reading ability at Time 2 varied considerably, from inability to read any words to word-reading ability slightly above the level expected for age. The results of a multiple regression indicated that Time 1 word-reading instruction type, phonological awareness, and visual-spatial perception (as assessed by a matching letter-like forms measure) each explained significant unique variance in word reading at Time 2. A systematic phonics approach was associated with significantly better performance than other reading-instruction approaches. Exploratory analyses suggested that the relations between these factors were complex. Considered together, these findings strongly suggest that, in line with the Cumulative Risk and Resilience Model of reading disability, word-reading (dis)ability in Williams syndrome is probabilistic in nature, resulting from the interaction of multiple individual and environmental risk and protective factors. The results also have educational implications: early word-reading instruction for children with Williams syndrome should combine systematic phonics and phonological awareness training while also incorporating letter discrimination instruction highlighting the visual-spatial differences between similar-appearing letters.

Many people with intellectual disabilities (ID) depend on caregivers for pain identification and pain management decisions. Therefore, the aim was to explore caregivers' experience with pain in Prader-Willi syndrome (PWS), Williams syndrome (WS), and Fragile-X syndrome (FXS). A questionnaire was developed to gather third-party reporting of mainly pain presence, expression, and coping. Questions had single or multiple choice answers and open text fields, without verification of the putative information. The questionnaire was sent digitally to associations and interest groups for the syndromes and healthcare institutions for people with ID. After excluding absent, unknown, or uncertain genetic diagnoses and people without ID, the remaining 243 responses originated by caregivers (90.6% parents) of children and adults with PWS (n = 165), WS (n = 53), and FXS (n = 25) in English, French, Dutch, and German speaking countries. More than half of all respondents reported the presence of known physical conditions that could be painful (58.4%) and pain observed during the past three months (54.3%, of which 70.9% chronic). Results reveal caregivers' barriers in identifying pain (e.g., interpreting pain expression and sensitivity). Respondents cope with pain mainly by seeking (para) medical help and observe both passive and active coping in people with the syndromes. Within limitations of the study's scope and design (e.g., used questionnaire), the results open a discussion about the validity of caregivers's perspective on pain. In-depth analysis in a more representative sample is recommended, as well as solutions for clinical practice such as training and education material about pain.

This cross-sectional and descriptive study examined the family quality of life (FQoL) among 72 Brazilian families who have children with Williams syndrome, a rare genetic disorder in which most individuals have an intellectual disability, usually mild. Data were collected using sociodemographic and clinical data forms and the Beach Center FQoL Scale. The overall FQoL score was 3.90 ± 0.45, below the limit of four points considered satisfactory. Families felt more satisfied with the family interaction (4.11 ± 0.57), parenting (4.07 ± 0.42), and disability-related support (3.94 ± 0.62) domains, and less satisfied with the family's emotional (3.49 ± 0.73) and physical/material well-being (3.73 ± 0.74) domains. Paternal education, children's cardiopathy and autonomy in activities of daily living explained 24.5% of the variance in the overall FQoL. Measures are necessary to improve the emotional and physical/material well-being of families to reduce the family burden. Monitoring the child's cardiac condition and promoting independence in activities of daily living are also the main procedures.

Increased attention is arising on the delivery of remote cognitive interventions, which allow performing exercises in everyday settings, favouring rehabilitation continuity. The present study offers an overview of remote cognitive training programs for children with congenital brain malformation or genetic syndrome affecting the central nervous system, included in papers published in the time period 2011-2021. A total of 13 records was found and discussed including efficacy studies, feasibility studies and study protocols. Many studies have focused on a specific diagnosis, such as cerebral palsy, Down Syndrome, Fragile X Syndrome, while no or little evidence has been gathered on more rare diseases or brain malformations. Interventions were found to generate benefits on some cognitive functions, but problems with adherence were highlighted, especially due to excessive cognitive load from the training or clinical comorbidities. Conclusions remain tentative due to heterogeneity in training, study and patients characteristics, and methodological limitations of studies.

The purpose of the manuscript is to present to academic teachers, doctors and nutritionists how practical online classes with dietetics students can be used to develop ready-made tools at work and for the education of phenylketonuria (PKU) patients and their caregivers/parents. During online classes in 2020, as part of the subject--diet therapy of metabolic blocks, 53 students prepared PKU sandwiches at home. Each PKU sandwich has a calculated nutritional value, and phenylalanine exchanger content, but does not include low-protein bread. The selection of a particular type of PKU bread depends solely on the PKU patient, hence it was deliberately not included in the calculations. The sandwiches, made by students and assessed by academic teachers, will be published with the following title "The PKU Sandwiches Album". The Album with more than 400 colorful pictures of PKU sandwiches, will be expected to inspire patients and help them add appeal to their diet, enriching it with new tastes, at the same time facilitating the memorizing process of ingredients, thanks to visualization and presented calculations, and motivating them to comply with strict dietary recommendation. The same nutritional calculations and ideas for sandwiches, with the use of different bread, e.g., gluten-free, may be useful in other diseases, such as celiac disease.

"DDX[subscript 3]X" variants are a common cause of intellectual disability (ID) in females, and have been associated with autism spectrum disorder and emotional-behavioural difficulties. In this study, we compared phenotypic data for 23 females with "DDX[subscript 3]X" variants, to 23 females with ID and other genetic diagnoses. We found a wide range of adaptive, social and emotional function within the "DDX[subscript 3]X" group. Autism characteristics did not differ between "DDX[subscript 3]X" and comparison groups, while levels of anxiety and self-injurious behaviour (SIB) were significantly higher in the "DDX[subscript 3]X" group. Within the "DDX[subscript 3]X" group, adaptive function, autism characteristics, anxiety and SIB scores were positively correlated, with evidence for group-specific associations with SIB. Future work is warranted to explore the multilevel mechanisms contributing to social and emotional development in individuals with "DDX[subscript 3]X" variants.

Individuals with Sex Chromosome Trisomies (SCT; XXX, XXY, XYY) have an increased vulnerability for developing challenges in social adaptive functioning. The present study investigates social interaction behavior in the context of varying social load, and Autism Spectrum Disorder (ASD) symptomatology in young children aged 1-7.5 years old, with SCT (N = 105) and control children (N = 101). Children with SCT show less interaction behaviors and more social withdrawal, as compared to their control peers, which were most evident in the high social load condition. Second, social impairments related to ASD are more prevalent, as compared to controls (27.1% at clinical level). These findings stress the importance of early monitoring and (preventive) support of early social development in young children with SCT.

Sleep problems are prevalent among autistic children and children with Rare Genetic Neurodevelopmental Disorders (RGND). Behavioral interventions are commonly used to treat sleep problems, with most involving extinction. While effective, the occurrence of a response burst (i.e., temporary worsening of the behavior) can result in a temporary increase in parent and child distress, and negatively affect treatment adherence. Thus, it is important to develop less restrictive treatment options. This study used a single case multiple baseline design to investigate the effectiveness and acceptability of less restrictive behavioral interventions (i.e., specifically excluding extinction) for sleep problems in ten autistic children and children with RGND (M = 7.3 years). Results demonstrated a reduction in sleep disturbance including unwanted bed-sharing, night wakings and sleep onset delay for 3/3, 5/5 and 6/7 children respectively, which were maintained at follow-up. Interventions were rated favorably by parents. The clinical implications of these findings are discussed.

Williams syndrome (WS) is a rare genetic condition associated with high sociability, intellectual disability, and social cognitive challenges. Attention to others' eyes is crucial for social understanding. Orienting to, and from other's eyes was studied in WS (n = 37, mean age = 23, age range 9-53). The WS group was compared to a typically developing comparison participants (n = 167) in stratified age groups from infancy to adulthood. Typically developing children and adults were quicker and more likely to orient to eyes than the mouth. This bias was absent in WS. The WS group had reduced peak saccadic velocities, indicating hypo-arousal. The current study indicates reduced orienting to others' eyes in WS, which may affect social interaction skills.

This study investigated sex and age differences in autistic behaviours in children with neurofibromatosis type 1 (NF1) who scored within the clinical range on the Social Responsiveness Scale - Second Edition (T score [greater than or equal to] 60). Thirty-four males and 28 females (3-16 years) were assessed with the Autism Diagnostic Observation Schedule - Second Edition and Autism Diagnostic Interview - Revised. Across both measures, males exhibited greater social communication deficits relative to females. Age-related abatement of social communication difficulties was observed for males but not females. Conversely, no sex differences were found for restricted/repetitive behaviours, which were stable over time for both males and females. The findings are discussed within the context of broader neurodevelopmental considerations that are common in NF1.