This study examines the course of intelligence in children with neurofibromatosis type 1 (NF1) and factors influencing changes. In this cross-sectional and longitudinal study, 397 children were assessed at ages 3, 6, 11, and 15 years using a neuropsychological test battery. Comparisons of demographics and scores were conducted across and within cross-sectional and longitudinal groups. Cross-sectionally, 15-year-olds outperformed 11-year-olds on Performance IQ (PIQ). A reduced PIQ at age 11 years was found that appeared to recover by age 15 years in the longitudinal group. The mother's level of education, the mode of inheritance, or attention-deficit hyperactivity disorder were not predictive of these changes. Overall, intelligence remains stable in children with NF1 between 3 and 15 years of age. The gap between PIQ and VIQ decreases over time. Neurocognitive monitoring is recommended during the critical period between ages 6 and 11 years due to risks of attention and learning issues.

Objective Children with the autosomal dominant disorder Neurofibromatosis 1 (NF1) exhibit a high prevalence of both attention-deficit/hyperactivity disorder (ADHD) (up to 40%) and autism (up to 11%). The genetic mechanisms underlying these behavioral phenotypes are largely unexplored. This study examines the associations between various NF1 genotypes and NF1 behavioral phenotypes. Method A retrospective cohort study was carried out in children and adolescents with NF1 from three national referral centers for NF1 (the Netherlands, the UK and Belgium). Anonymized data was collected on five primary outcomes to characterize the behavioral phenotype in NF1: autistic traits (Social Responsiveness Scale 2 [SRS-2] Total T-score and Autism Diagnostic Observation Schedule [ADOS] Calibrated Severity Score); attention-deficit/hyperactivity disorder characteristics (Conners Inattention and Hyperactivity T-score) and global behavioral/emotional problems (Child Behavior Checklist [CBCL] Total Problems T-score). Genotypes were categorized based on three types of NF1 variant definitions: (1) coding variant type, (2) variant effect (truncating vs. non-truncating variants), and (3) the location within the gene. Results In total, 408 children and adolescents with NF1 were included, of which 187 (46%) were female. Range of median age at assessment across all outcomes was 6.0-8.4 years. Behavioral outcomes were not associated to any of the NF1 genotypes categories examined. Conclusion In this large cohort, autism traits, ADHD characteristics or global behavioral/emotional problems were not associated with NF1 variant type, effect or location. These findings indicate that the NF1 variant classes examined here do not differentially influence the NF1 behavioral phenotype, although genotype–phenotype associations at the single codon level cannot be ruled out.

OBJECTIVE:Efficient screening for neurocognitive dysfunction is pivotal for timely intervention in at-risk populations in pediatrics. The Pediatric Perceived Cognitive Functioning (PedsPCF) item bank was developed for this purpose. We aimed to explore the relationship between, and the discriminative value of PedsPCF scores with neurocognitive outcomes and the behavior rating inventory of executive function parent report (BRIEF) in a pediatric population. METHODS:The PedsPCF parent- and self-report versions were added to neurocognitive testing batteries that were administered in clinical care or research in two Dutch academic pediatric hospitals. Most test batteries were individually tailored, resulting in a wide variety of measures. We determined Pearson correlations between the PedsPCF and neurocognitive test outcomes categorized into five neurocognitive domains as proposed in the Diagnostic and Statistical Manual of Mental Disorders-5, and the BRIEF-parent. Moreover, we assessed the discriminative values of PedsPCF deficit scores (M - 1 SD) for neurocognitive domain deficits (M - 1 SD) and the BRIEF-parent. RESULTS:The PedsPCF was completed by 104 children and 106 parents. The parent-PedsPCF correlated with three neurocognitive domains and the BRIEF-parent but did not indicate deficits in any of the neurocognitive domains. The self-report PedsPCF correlated with a deficit in complex attention and the BRIEF-parent, and could indicate a deficit in complex attention only. CONCLUSIONS:Although the PedsPCF correlated with neurocognitive test outcomes, the discriminative value of the total score was limited. The short and freely available PedsPCF appears to add a useful subjective dimension to neurocognitive testing rather than a replacement of neurocognitive assessment.

Angelman syndrome (AS) is a rare neurogenetic disorder. Previous studies indicate a high prevalence of autism spectrum disorder (ASD) with considerable variability. Little is known regarding the longitudinal trajectory of autistic traits. We aim to investigate autistic traits, the effect of age on these traits, and associated features in AS children. This (partly) longitudinal clinical record study at the ENCORE Expertise Center involved 107 AS children aged 2-18 with one (N = 107), two (N = 49), or three (N = 14) measurements. Autistic traits and sensory processing issues were assessed using various instruments, and DSM classifications were used descriptively. Covariates were genotype, gender, and epilepsy. Results indicate a high prevalence of autistic traits and sensory processing issues. Children with the deletion genotype exhibited more autistic traits. Autism Diagnostic Observation Schedule (ADOS) classifications indicated higher rates of ASD compared to clinician DSM classifications. Autistic traits generally remained stable over time, except that ADOS scores significantly decreased for children with the UBE3A mutation genotype, and in the social affect domain for the entire group. In conclusion, incorporating the assessment of autistic traits and sensory processing into clinical practice for AS is important to inform adaptations of the environment to meet the child's needs. Additionally, clinicians and researchers should be mindful of the potential for overestimating ASD traits in AS when relying on the ADOS. ASD diagnosis in AS should integrate multiple diagnostic instruments, diverse hetero-anamnestic sources, and multidisciplinary expert opinions.

Sensory processing (SP) difficulties, such as heightened sensitivity to sensory input, have been linked to prolonged recovery and persistent post-concussive symptoms in adults following mild traumatic brain injury (mTBI). However, research on SP across different sensory inputs after pediatric mTBI is limited. This study examined SP patterns in children and adolescents aged 6-17 years with mTBI at 2 weeks and 6 months post-injury. Caregivers of children aged 6-11 years (n = 120) completed the Short Sensory Profile - Dutch version (SSP-NL), while adolescents aged 12-17 years (n = 121) completed the Adolescent/Adult Sensory Profile - Dutch version (AASP-NL), and scores were compared to normative data. Multilevel latent class growth analysis (MLCGA) identified four SP classes in children: (1) taste and smell sensitivity, (2) general hypersensitivity, (3) general hyposensitivity, and (4) under responsiveness with auditory filtering issues. Class 2 showed lower Child and Adolescent Scale of Participation (CASP) scores. SP changes over time were limited, with persistent issues (of hyper- and hyposensitivity) at 6 months. For adolescents, two classes were found: (1) avoidant and passive, and (2) mild, with Class 1 showing lower CASP scores. Class 2 exhibited reductions in poor registration, sensory sensitivity, and sensation avoidance over time. These findings highlight inter-individual differences in SP after pediatric mTBI, with subgroups differing in how they affect activities and participation. Early identification of SP issues may help tailor more effective interventions.

Abstract Background Individuals with neurofibromatosis type 1 (NF1) frequently report psychosocial problems, among which internalizing and externalizing symptoms are the most poorly understood due to limited research and inconsistent evidence. This hinders the overall attendance of their psychosocial needs and has a major impact on their quality of life. Thus, this systematic review and meta-analysis was conducted to synthesize existing findings on the degree to which individuals with NF1 experience internalizing and externalizing symptoms, compared with the unaffected population, and explore moderators of the group disparities. Methods Scopus, PsycINFO, Web of Science, PubMed, and ProQuest were searched from inception to March 26th, 2024, which identified 59 eligible studies (N of NF1 = 3182, mean ages 2.38 to 46.4 years). Hedges’ g was calculated for differences in internalizing and externalizing symptoms between the NF1 group and the unaffected controls. Study effect sizes were pooled using robust variance estimation and random-effects models. Moderators of group differences were tested using meta-regression. Results Random-effects meta-analyses indicated that compared with unaffected controls, individuals with NF1 showed more severe depressive (k = 21; g = 0.43; 95% CI [0.21, 0.65]), anxiety (k = 24; g = 0.27; 95% CI [0.01, 0.54]), somatic (k = 27; g = 0.56; 95% CI [0.30, 0.83]), total internalizing (k = 75; g = 0.50; 95% CI [0.33, 0.67]), aggression (k = 33; g = 0.33; 95% CI [0.08, 0.58]), delinquency, (k = 37; g = 0.43; 95% CI [0.26, 0.60]), and total externalizing symptoms (k = 47; g = 0.24; 95% CI [0.13, 0.35]). Studies that included more participants with NF1 who had ADHD or a lower verbal IQ reported greater group disparities in total internalizing symptoms or aggression. Conclusions Findings highlight the importance of promptly recognizing internalizing and externalizing symptoms in individuals with NF1 for timely interventions. Future research should identify predictors of internalizing and externalizing symptoms within the NF1 population to inform our knowledge and intervention development. Other implications for future research were also discussed. Systematic review registration The study protocol of this meta-analysis was registered at PROSPERO (CRD42023478258).

BACKGROUND:As more neonates born with congenital diaphragmatic hernia (CDH) survive, interest in long-term morbidities and their health-related quality of life (HRQoL) is growing. For adolescents and young adults with CDH, information on HRQoL is anecdotal. Therefore, our aim was to evaluate HRQoL and its determinants in a recently studied cohort of adult CDH survivors. METHODS:We conducted a prospective, nationwide observational cohort study in CDH patients born 1989 to 2001. Demographic and clinical characteristics were collected, and participants completed questionnaires assessing HRQoL, participation and autonomy, fatigue, and emotional and behavioral wellbeing. Descriptive and inferential statistical analyses were performed. RESULTS:Sixty-one CDH patients aged 19-31 years were included. Overall, participants experienced normal HRQoL for both physical (mean (SD) z-score: 0.03 (1.01); p = 0.088) and mental (z-score -0.23 (1.05); p = 0.316) components. Their participation and autonomy exceeded that of a reference population with one chronic disorder (p < 0.001), but they experienced significantly more fatigue (z-score: -0.46 (1.24); p = 0.006); which was severe in 16 %. Patients reported significantly more frequent internalizing problems, particularly within the 'somatic complaints' domain (p = 0.004). Among positive determinants of physical HRQoL were attendance of regular education, a higher exercise capacity, and better outdoors autonomy. Positive determinants of mental HRQoL included undergoing primary diaphragmatic repair and having fewer internalizing problems. CONCLUSIONS:CDH patients perceive their HRQoL to be comparable to that of the general population, achieving similar participation and autonomy. However, fatigue warrants attention during long-term follow-up, and psychological counseling in childhood and adolescence may be beneficial for addressing emotional problems. LEVEL OF EVIDENCE:Not applicable.

Persons living with a rare disease (PLWRD) often encounter burdensome and stressful events that may severely affect their psychosocial vulnerability. There is an urgent need for psychosocial support in PLWRD. We aimed to reach consensus about the most prominent psychosocial needs in rare diseases and future research directions to develop adequate psychosocial support for rare diseases. An adapted nominal group technique (NGT) session was conducted in Nijmegen (The Netherlands) with a European expert group of professionals working in the rare disease field. Seventeen participants from seven different European countries took part in the NGT session (seven researchers, two therapists, one patient representative, four clinicians/researchers, and three clinicians), and 23 participants took part in the overall workshop and contributed to this consensus statement. An initial list of 57 psychosocial needs was aligned with Pickers’ theoretical framework of eight principles of care: patient-centredness, emotional support, access to care, information and education, partner and family involvement, respect and autonomy, care organisation, continuity of care, and physical comfort. For future research directions, six items remained with main focal points addressing international collaborations, inclusivity in rare diseases (patient representatives, ethnic minorities, and elderly), identifying common needs across rare diseases, and translating psychosocial models from common chronic conditions. A consensus meeting was organised that primarily addressed the psychosocial vulnerability in rare diseases. With the outcomes of this study, we aim for better representation of psychosocial vulnerability within health care and to create future research directions to reduce psychosocial vulnerability in rare diseases.

Studying Autism Spectrum Disorder (ASD) heterogeneity in biologically homogeneous samples may increase our knowledge of ASD etiology. Fragile X syndrome (FXS), Angelman syndrome (AS), Tuberous Sclerosis Complex (TSC), and Neurofibromatosis type 1 (NF1) are monogenic disorders with high a prevalence of ASD symptomatology. This study aimed to identify ASD symptom profiles in a large group of children and adolescents (0;9–28 years) with FXS, AS, TSC, and NF1. Data on ASD symptomatology (Autism Diagnostic Observation Scale (ADOS-2) Social Responsiveness Scale (SRS-2)) were collected from children and adolescents with FXS (n = 54), AS (n = 93), TSC (n = 112), and NF1 (n = 278). To identify groups of individuals with similar ASD profiles, we performed two latent profile analyses. We identified a four-profile model based on the ADOS-2, with a (1) ‘Non-spectrum symptom profile’, (2) ‘Social Affect symptom profile’, (3)‘Restricted/Repetitive Behaviors symptom profile’, and (4)‘ASD symptom profile’. We also identified a four-profile model based on the SRS, with a (1)‘Non-clinical symptom profile’, (2)‘Mild symptom profile’, (3)‘Moderate symptom profile’, and (4)‘Severe symptom profile’. Although each syndrome group exhibited varying degrees of severity, they also displayed heterogeneity in the profiles in which they were classified. We found distinct ASD symptom profiles in a population consisting of children and adolescents with FXS, AS, TSC, and NF1. Our study highlights the importance of a personalized approach to the identification and management of ASD symptoms in rare genetic syndromes. Future studies should aim to include more domains of functioning and investigate the stability of latent profiles over time.

AIM:To find proof-of-principle evidence for short-term treatment with lamotrigine to improve cognitive functioning of adolescents with neurofibromatosis type 1 (NF1). METHOD:This was a double-blind, parallel-group, randomized, placebo-controlled clinical trial (the NF1-EXCEL trial: Examining the Cognitive and Electrophysiological benefit of Lamotrigine in Neurofibromatosis type 1; Clinicaltrials.gov identifier NCT02256124), with the aim of enrolling 60 adolescents with NF1 aged 12 to 17  years 6 months. The short-term study intervention was 200 mg of lamotrigine taken orally for 26 weeks. The primary outcome was performance IQ tested with the Wechsler Intelligence Scale for Children, Third Edition, complemented with secondary outcomes for visuospatial learning efficacy, visual perception, visual sustained attention, fine motor coordination, attention-deficit/hyperactivity problems, and executive functioning. RESULTS:We screened 402 adolescents with NF1, of whom 31 (eight females) entered the study. Complete-case analysis showed no effect of lamotrigine on either performance IQ (-0.23, 95% CI -6.90 to 6.44) or most secondary outcomes. Visual sustained attention showed a trend towards better performance in the lamotrigine group (-0.81, 95% CI -1.67 to 0.04). INTERPRETATION:Lamotrigine did not improve cognitive functioning in adolescents with NF1. The small treatment effects make it unlikely that a larger sample size could have changed this conclusion.

Background: Infants with infantile hemangioma (IH) have been effectively treated with propranolol or atenolol. Concerns were raised about the mental health of these children at school age, due to central nervous system effects of propranolol and visible nature of IH. Objective: This study aimed to compare the mental health at school age of children treated with propranolol to children treated with atenolol for IHs and their parents. Methods: This two-centered cross-sectional study included children aged ≥6 years and treated with either propranolol or atenolol for IH during infancy. Children’s outcomes were performance-based affect recognition (Dutch version of the Developmental Neuropsychological Assessment-II [NEPSY-II-NL]), parent-reported emotional and behavioral functioning (Child Behavioral Checklist [CBCL]), and health-related quality of life (KIDSCREEN-27). Parents’ outcome was parenting stress (Parenting Stress Questionnaire [OBVL]). Results: Data of 105 children (36 propranolol, 69 atenolol; 6.0–11.8 years) were analyzed. Mental health outcomes did not differ between both β-blocker groups. Although overall functioning was in line with norms, children presented specific problems concerning affect recognition, parent-reported attention, and social quality of life. Parents showed increased physical symptoms, depressive symptoms, and parent-child relationship problems. Conclusion: No difference in mental health at school age was found between children treated with propranolol or atenolol for IH. Although few overall mental health problems were found, specific problems require follow-up. Follow-up of children should be directed toward affect recognition, attention, and social functioning in daily life. Problems reported by parents could be ameliorated by mental health support during and after their infant’s β-blocker treatment.

Background Many rare genetic neurodevelopmental disorders (RGNDs) are characterized by intellectual disability (ID), severe cognitive and behavioral impairments, potentially diagnosed as a comorbid autism spectrum disorder or attention-deficit hyperactivity disorder. Quality of life is often impaired due to irritability, aggression and self-injurious behavior, generally refractory to standard therapies. There are indications from previous (case) studies and patient reporting that cannabidiol (CBD) may be an effective treatment for severe behavioral manifestations in RGNDs. However, clear evidence is lacking and interventional research is challenging due to the rarity as well as the heterogeneity within and between disease groups and interindividual differences in treatment response. Our objective is to examine the effectiveness of CBD on severe behavioral manifestations in three RGNDs, including Tuberous Sclerosis Complex (TSC), mucopolysaccharidosis type III (MPS III), and Fragile X syndrome (FXS), using an innovative trial design. Methods We aim to conduct placebo-controlled, double-blind, block-randomized, multiple crossover N -of- 1 studies with oral CBD (twice daily) in 30 patients (aged ≥ 6 years) with confirmed TSC, MPS III or FXS and severe behavioral manifestations. The treatment is oral CBD up to a maximum of 25 mg/kg/day, twice daily. The primary outcome measure is the subscale irritability of the Aberrant Behavior Checklist. Secondary outcome measures include (personalized) patient-reported outcome measures with regard to behavioral and psychiatric outcomes, disease-specific outcome measures, parental stress, seizure frequency, and adverse effects of CBD. Questionnaires will be completed and study medication will be taken at the participants’ natural setting. Individual treatment effects will be determined based on summary statistics. A mixed model analysis will be applied for analyzing the effectiveness of the intervention per disorder and across disorders combining data from the individual N -of- 1 trials. Discussion These N -of- 1 trials address an unmet medical need and will provide information on the effectiveness of CBD for severe behavioral manifestations in RGNDs, potentially generating generalizable knowledge at an individual-, disorder- and RGND population level. Trial registration EudraCT: 2021-003250-23, registered 25 August 2022, https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-003250-23/NL .

Abstract Introduction Congenital abdominal wall defects (AWD) such as gastroschisis (GS) and omphalocele (OC) are malformations associated with morbidity, especially early in life. Our aim was to identify if screening instruments for mental health indicate elevated levels of difficulties. Method A systematic literature review complying with a PRISMA-protocol (PROSPERO, CRD42023443731) was undertaken. A search across five databases, focusing on mental health difficulties during childhood was conducted. Result Out of 450 articles identified, six were included, in total 168 children (median sample size; 31, range 16-38) covering an age range of 5-17 years. The studies were all cross- sectional, single-centre, originating in the Netherlands(n=3), Australia(n=2), and the USA(n=1),using parent’s reports of the instruments Strength and Difficulties Questionnaire (SDQ), (n=3), Child Behaviour Check List (CBCL), ( n=2) and Behaviour Assessment System for Children –Second Edition (BASC-2), (n=1). In most studies, the AWD group had a higher prevalence of mental health difficulties. Two studies showed that children with AWD had significantly higher levels of difficulties in at least one domain of mental health, while the other four studies found no significant differences. Discussion Screening instruments for mental health difficulties show different results regarding children born with an AWD. A subgroup reported mental health difficulties, but not always significantly more than in the healthy normative population, but previous studies have employed small sample sizes and have lacked the statistical power to detect differences. More research, preferably with larger samples from multiple centres is warranted.

Background: The long-term effects of childhood surgery scars on health status, quality of life (QoL), selfesteem, and body image remain uncertain. This study explores these effects in school-aged children. Methods: We conducted a retrospective cohort study involving 454 children (58% boys; 8-17 years) who had undergone surgical correction of anatomical anomalies or neonatal ECMO. Data included patientreported scar perception and scar-related embarrassment, along with psychological assessment via questionnaires. Results: About 34% of children rated their scars as 'nice-looking', 49% as 'indifferent', and 12% as 'rather ugly'. Most children (91%) never experienced scar-related embarrassment, while frequent embarrassment was reported by 3%. Surgical scar correction was desired by 6% of the 8-year-olds and 19% of the 17year-olds. Scar perception did not significantly affect health status or QoL. However, negative scar perception was associated with lower self-esteem in girls and a more negative body image in boys. Girls were more likely to report negative scar perception (OR: 1.54, 95%-CI: 1.06-2.24) and scar-related embarrassment (OR: 4.29, 95%-CI: 1.77-10.4 4). Conclusion: Children who underwent surgery in the neonatal period and subsequently grew up with scars resulting thereof, mostly perceive them either indifferently or positively, with minimal effect on health status and QoL. Nonetheless, some children, particularly girls, experienced negative perceptions of their scars, although scar-related embarrassment was rare. We recommend integrating scar assessment into routine follow-up at ages 12 and 17, and offering appropriate and timely guidance and support to children at risk for negative effects of scars. Level of Evidence: III. (c) 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

The long-term neurodevelopment of children born with oesophageal atresia (OA) is unclear. Therefore, we assessed the neurocognitive domains and their predictors. Patients born with OA between February 2006 and December 2014, who were routinely seen at eight years as part of a structured prospective longitudinal follow-up program, were included. Main outcome measures were need for school support, performance in various neurocognitive domains and potential predictors of neurocognitive problems. We analysed data of 65 children with a mean (SD) age of 8.1 (0.2) years, of whom 89% with OA type C. Thirty-five (54%) surgical corrections were minimally invasive; the median (interquartile range) duration of exposure to anaesthetics in the first 24 months was 398 (296 – 710) minutes. Forty-four (68%) attended regular education without extra support and intelligence was within normal range (99–108). More than 50% had z-scores ≤ -2 on one or more neurocognitive domains, of which attention was the most frequently affected domain. The speed on the sustained attention task was significantly below normal (z-score -1.48 (2.12), p < .001), as was fluctuation of sustained attention (z-score -3.19 (3.80), p < .001). The minimally invasive approach and a lower socio-economic status (both p = 0.006) proved significant predictors for sustained attention problems in multivariable analyses. Conclusion : Children who undergo minimally invasive surgery for OA correction are at risk for sustained attention problems at school age. Future studies unravelling the effects of perioperative events on neurodevelopment should lead to optimal surgical, anaesthesiological, and intensive care management in the neonatal period. What is Known: • School-aged children born with oesophageal atresia have normal intelligence but problems with sustained attention at eight years. What is New: • Oesophageal atresia patients, who undergo minimally invasive surgery or who have a background of lower socioeconomic status are at serious risk for sustained attention problems at school age. • Moreover, those who have been intubated for a longer period are at risk for stronger fluctuations in sustained attention.

INTRODUCTION:Patient-reported outcome measures (PROMs) can be employed in both research and clinical care to enhance our understanding of outcomes that matter to patients. This narrative review aims to describe PROM use in recent pediatric surgical research, identify and describe psychometrically robust PROMs, providing an overview of those derived from pediatric patient input, and make recommendations for future research.MATERIALS AND METHODS:A search was conducted to identify articles published from 2021 to August 2023 describing the availability and/or use of at least one valid or reliable PROM in children with conditions including anorectal malformations, biliary atresia, congenital diaphragmatic hernia, duodenal atresia, esophageal atresia, abdominal wall defects, Hirschsprung's disease, sacrococcygeal teratoma, and short bowel syndrome. Articles were categorized based on their objectives in applying PROMs. Psychometrically robust PROMs were identified and described.RESULTS:Out of the 345 articles identified, 49 met the inclusion criteria. Seventeen focused on esophageal atresia and 14 on Hirschsprung's disease. Twenty-nine PROMs were identified, with 12 deemed psychometrically robust. Seven psychometrically robust PROMs were developed using patient input in the primary item generation. Most PROMs were applied to advance understanding of conditions and/or treatment and fewer were developed or psychometrically evaluated. No PROMs were assessed for their impact or incorporated into an implementation study.CONCLUSIONS:This review reveals gaps in the application of PROMs in recent pediatric surgical research. Emphasis should be placed on the development and utilization of psychometrically robust PROMs, broadening the scope of covered diseases, conducting impact assessments, and evaluating implementation strategies.

IntroductionChildren with atopic dermatitis (AD) are more at risk for the neurodevelopmental disorders attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) with parallel increases in global prevalences. Children afflicted with these conditions appear to share similar problems in sensory modulation but investigational studies on the underlying aetiology are scarce. This scoping review aims to find knowledge gaps, collate hypotheses and to summarise available evidence on the shared pathophysiology of AD, ADHD and ASD in children.Methods and analysisOur study will follow the methodological manual published by the Joanna Briggs Methodology for Scoping Reviews and will be reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews. The following electronic databases will be searched for studies focused on children with AD and symptoms of ADHD and/or ASD: Medline ALL via Ovid, Embase, Web of Science Core Collection and the Cochrane Central Register of Controlled Trials via Wiley.Ethics and disseminationThis review does not require ethics approval as it will not be conducted with human participants. We will only use published data. Our dissemination strategy includes peer review publication and conference reports.

Background/Objectives: The disparities in internalizing and externalizing symptoms between individuals with versus without neurofibromatosis type 1 (NF1) are poorly understood, based on mixed evidence in the literature. The current meta-analysis aimed to synthesize existing findings on the topic and explore moderators of the group disparities. Method: Electronic databases were searched from inception to March 26th 2024, which identified 59 eligible studies (N of NF1 = 3,182, mean ages 2.38 to 46.4 years). The primary outcome was differences in internalizing and externalizing symptoms between individuals with and without NF1. Data were analyzed using robust variance estimation and random-effects models. Results: Compared with unaffected controls, individuals with NF1 showed more severe depressive (k = 21; g = 0.43; 95% CI [0.21, 0.65]), anxiety (k = 24; g = 0.27; 95% CI [0.01, 0.54]), somatic (k = 27; g = 0.56; 95% CI [0.30, 0.83]), total internalizing (k = 75; g = 0.50; 95% CI [0.33, 0.67]), aggression (k = 33; g = 0.33; 95% CI [0.08, 0.58]), delinquency, (k = 37; g = 0.43; 95% CI [0.26, 0.60]), and total externalizing symptoms (k = 47; g = 0.24; 95% CI [0.13, 0.35]). Studies that included more participants with NF1 who had ADHD or a lower verbal IQ reported greater group disparities in total internalizing symptoms or aggression. Conclusions: Findings highlight the importance of including psychosocial needs in monitoring and treating NF1. Future research should identify predictors of internalizing and externalizing symptoms within the NF1 population to inform our knowledge and intervention development.

Background Tuberous sclerosis complex (TSC) is a rare and complex genetic disorder, associated with tumor growth in various organ systems, epilepsy, and a range of neuropsychiatric manifestations including intellectual disability. With improving patient-centered care and targeted therapies, patient-reported outcome measures (PROMs) are needed to measure the impact of TSC manifestations on daily functioning. The aim of this study was to develop a TSC-specific PROM for adults that captures the impact of TSC on physical functions, mental functions, activity and participation, and the social support individuals with TSC receive, called the TSC-PROM. Methods COSMIN methodology was used to develop a self-reported and proxy-reported version. Development and validation consisted of the following studies: PROM development, content validity, structural validity, internal consistency, and construct validity. The International Classification of Functioning and Disability was used as a framework. Content validity was examined by a multidisciplinary expert group and cognitive interview study. Structural and construct validity, and internal consistency were examined in a large cohort, using confirmatory factor analysis, hypotheses testing, and Cronbach’s alpha. Results The study resulted in an 82-item self version and 75-item proxy version of the TSC-PROM with four subscales (physical functions 18 and 19 items, mental functions 37 and 28 items, activities and participation 13 and 14 items, social support 13 items, for self version and proxy version respectively). Sufficient results were found for structural validity with sufficient unidimensionality for each subscale. With regard to construct validity, 82% of the hypotheses were met for the self version and 59% for the proxy version. The PROM showed good internal consistency (Cronbach’s alpha 0.78–0.97). Conclusions We developed a PROM for adults with TSC, named TSC-PROM, showing sufficient evidence for reliability and validity that can be used in clinical and research settings to systematically gain insight into their experiences. It is the first PROM in TSC that addresses the impact of specific TSC manifestations on functioning, providing a valuable, patient-centered addition to the current clinical outcomes.