Introduction: Tuberous sclerosis complex (TSC) is a rare genetic multisystem disorder characterized by the widespread growth of benign hamartomas in multiple organ systems, leading to very diverse ...Show moreIntroduction: Tuberous sclerosis complex (TSC) is a rare genetic multisystem disorder characterized by the widespread growth of benign hamartomas in multiple organ systems, leading to very diverse (neuropsychiatric) manifestations, including autism spectrum disorder (ASD). This study aimed to examine the prevalence of clinically assessed ASD in children with TSC visiting a specialized TSC outpatient clinic. The influence of gender, age, intellectual functioning, and mutation type on a clinical ASD diagnosis was investigated. Secondly, the predictive value of using both a screening instrument and an observational assessment in relation to a clinical DSM-IV/-V ASD diagnosis in the group of children with TSC was examined. Methods: The data sample consisted of 110 children (50% male) between 1 and 17 years old (mean age = 9.65, SD = 4.61) diagnosed with a genetically and/or clinically confirmed diagnosis of TSC and a filled out ADOS and/or SRS. They were assessed as part of standard (mental) health care and longitudinal follow-up. The independent variables were gender, age, IQ/DQ, and mutation type, which associations with clinical ASD diagnoses were examined with Chi-Square Tests of Association or independent sample t-tests. The dependent variables were ASD classifications according to the Social Responsiveness Scale (SRS/SRS-2) scores, Autism Diagnostic Observation Schedule-second edition (ADOS-2) scores, and DSM-IV/-V diagnoses. Results: A clinical ASD prevalence rate of 52.7% was found, substantially higher than in the general population. Children with a clinical ASD diagnosis had significantly lower intelligence scores (p = .01). No gender, age, or mutation type effects were found. The combined use of screening and observational- based classifications showed the highest positive predictive value for DSM-IV/-V ASD diagnosis. Discussion: The results showed a substantially higher ASD prevalence rate compared to the general population, underlining the importance of ASD assessment in children with TSC. Furthermore, these results highlighted the relevance of using both a screening instrument and an observational assessment to accurately classify children with TSC as having ASD. A better ASD prediction and classification may lead to earlier diagnosis and appropriate, personalized interventions, potentially alleviating some of the burden for both patients and their families or caregivers.Show less
Introduction: Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders and has a major genetic heterogeneity. Comparing monogenetic causes of ASD can contribute to...Show moreIntroduction: Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders and has a major genetic heterogeneity. Comparing monogenetic causes of ASD can contribute to understanding its genetic aetiology. This study compares patients with fragile X syndrome (FXS) to patients with tuberous sclerosis complex (TSC) in terms of ASD severity and symptomatology to create an image of their ASD symptom profiles. This could lead to more focused diagnoses and specialized treatment for these patient groups. Methods: This study included children and adolescents (ages 1–18, mean age = 9.01 years) with FXS (n = 57, 80.7% males) or TSC (n = 105, 49.5% males). The second editions of the Autism Diagnostic Observation Scale and the Social Responsiveness Scale were used to assess ASD symptomatology. First, the prevalence of official ASD diagnoses among FXS and TSC patients was compared. Next, patients with an official diagnosis were compared in terms of (1) overall autism severity, (2) severity of problems within the restricted and repetitive behaviour (RRB) and social affect domains, and (3) more specific ASD symptoms such as ‘reciprocal communication’. Intelligence quotient (IQ; mean IQ = 58.08) was included as a predictor in the logistic regression and as a covariate in both between-group analyses of covariance and all multivariate analyses of covariance. Results: FXS patients are more likely to receive an official ASD diagnosis (χ2 = 4.081, p = .043). Higher IQ is related to less autism symptomatology (χ2 = 8.592, p = .003). Overall, ASD severity of patients with an official ASD diagnosis does not differ between the patient groups. The FXS patients with ASD exhibited more severe RRB (F = 8.21, p = .005). No significant difference was found for social affect or any specific symptoms. Conclusion: ASD prevalence is higher in children with FXS than in children with TSC, with FXS patients exhibiting more severe RRB. This study illustrates the relevance of comparing symptomatology in monogenetic causes of ASD, indicating that syndrome-symptom relationships can be found. This could lead to earlier intervention and focused treatment for these patients and contributes to research on the genetic aetiology of ASD.Show less
Background. Children with Tuberous Sclerosis Complex (TSC) are at a high risk for an intellectual impairment and experiencing psychiatric symptoms. Internalizing problems, such as anxiety and a...Show moreBackground. Children with Tuberous Sclerosis Complex (TSC) are at a high risk for an intellectual impairment and experiencing psychiatric symptoms. Internalizing problems, such as anxiety and a depressed mood, are among the most prevalent reported psychiatric symptoms in patients with TSC. These problems often precede more severe psychopathology, especially when they remain unrecognized. Despite this, research on this subject is still remarkably scarce, especially in children. A factor that seems to be positively associated with internalizing problems is intellectual ability. A major research question that arises is whether more internalizing problems are related to higher intelligence levels in children with TSC, which was examined in the current study. As TSC1 is related to less (severe) intellectual impairments compared to TSC2, a differentiation was made between these mutation types. Additionally, we explored whether internalizing problems increased with age, as would be consistent with findings in the general population. Methods. To test these hypotheses, internalizing problem scores (a parental report on the child behavior checklist) and intellectual ability (using different age- and range-appropriate intelligence and developmental tests) in a non-selected sample of children with TSC (N = 95, Age (Mean (SD) = 10.46 (4.25), 46.3% female, 28.5% TSC1) were assessed. To examine the association between internalizing problems and intellectual ability, several hierarchical regression analyses were performed. Externalizing problems, age, sex and the number of prescribed anti-epileptic drugs were included as control variables. For the exploratory hypothesis, this study tracked symptom severity over two follow-up visits in a subset of our patient population, using several paired sample t-tests. To additionally check whether internalizing problems became more severe in (early) adolescence we selected 15 children (66.7% female) for the childhood/adolescence subgroup. Within these groups, sex- and mutation related differences were also considered. Results. A significant model was found (F = 10.53, p <.001) in which externalizing problems (B = .55, p <.001) and age (B = .28, p <.005) were positively associated with internalizing problems. However, intelligence levels were found to have no influence. Furthermore, internalizing problems tend to increase with age (p <.001). Between childhood and adolescence, this increase was predominantly observed in girls (p = .03). Boys did not seem to experience more internalizing problems during this transition period. Lastly, a trend was found in which only a mutation on the TSC2 gene was associated with more internalizing problems over time (p <.005). Conclusion. This study could not confirm an association between internalizing problems and intelligence. However, our results indicated that internalizing problems increased with age, especially in girls. Since these behaviors contribute to the burden of the disease, it is of great importance that all involved professionals are sensitive to internalizing problems. A regular and thorough evaluation of internalizing problems should therefore always be part of the psychiatric assessment.Show less
