Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder characterized by intellectual disability, specific facial features, and marked autonomic nervous system dysfunction, especially with... Show morePitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder characterized by intellectual disability, specific facial features, and marked autonomic nervous system dysfunction, especially with disturbances of regulating respiration and intestinal mobility. It is caused by variants in the transcription factor TCF4. Heterogeneity in the clinical and molecular diagnostic criteria and care practices has prompted a group of international experts to establish guidelines for diagnostics and care. For issues, for which there was limited information available in international literature, we collaborated with national support groups and the participants of a syndrome specific international conference to obtain further information. Here, we discuss the resultant consensus, including the clinical definition of PTHS and a molecular diagnostic pathway. Recommendations for managing particular health problems such as dysregulated respiration are provided. We emphasize the need for integration of care for physical and behavioral issues. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimization of diagnostics and care. Show less
Objective: We aim to deliver a framework with 2 main objectives: 1) facilitating the design of theory-driven, adaptive, digital interventions addressing chronic illnesses or health problems and 2)... Show moreObjective: We aim to deliver a framework with 2 main objectives: 1) facilitating the design of theory-driven, adaptive, digital interventions addressing chronic illnesses or health problems and 2) producing personalized intervention delivery strategies to support self-management by optimizing various intervention components tailored to people's individual needs, momentary contexts, and psychosocial variables.Materials and Methods: We propose a template-based digital intervention design mechanism enabling the configuration of evidence-based, just-in-time, adaptive intervention components. The design mechanism incorporates a rule definition language enabling experts to specify triggering conditions for interventions based on momentary and historical contextual/personal data. The framework continuously monitors and processes personal data space and evaluates intervention-triggering conditions. We benefit from reinforcement learning methods to develop personalized intervention delivery strategies with respect to timing, frequency, and type (content) of interventions. To validate the personalization algorithm, we lay out a simulation testbed with 2 personas, differing in their various simulated real-life conditions.Results: We evaluate the design mechanism by presenting example intervention definitions based on behavior change taxonomies and clinical guidelines. Furthermore, we provide intervention definitions for a real-world care program targeting diabetes patients. Finally, we validate the personalized delivery mechanism through a set of hypotheses, asserting certain ways of adaptation in the delivery strategy, according to the differences in simulation related to personal preferences, traits, and lifestyle patterns.Conclusion: While the design mechanism is sufficiently expandable to meet the theoretical and clinical intervention design requirements, the personalization algorithm is capable of adapting intervention delivery strategies for simulated real-life conditions. Show less
Introduction Development and behaviour in Cornelia de Lange Syndrome (CdLS), including autism characteristics, have been described infrequently stratified to genetic cause and only a few studies... Show moreIntroduction Development and behaviour in Cornelia de Lange Syndrome (CdLS), including autism characteristics, have been described infrequently stratified to genetic cause and only a few studies have considered behavioural characteristics in relation to developmental level. Here, we describe the behavioural phenotype in individuals with CdLS with SMC1A variants. Methods We performed an international, interdisciplinary study on 51 individuals with SMC1A variants. Results of questionnaire studies are compared to those in individuals with Down Syndrome and with Autism Spectrum Disorder. Results on cognition and self-injurious behaviour (SIB) are compared to those in individuals with CdLS caused by NIPBL variants. For Dutch participants with SMC1A variants we performed direct in-person assessments of cognition, autism, and added an interview and questionnaire on adaptive behaviour and sensory processing. Results Individuals with SMC1A variants show a higher cognitive level and less SIB than individuals with NIPBL variants. Individuals with SMC1A variants without classic CdLS phenotype but with a Rett-like phenotype show more severe intellectual disability and more SIB compared to those with a CdLS phenotype. Autism is less present if outcomes in direct in-person assessments are evaluated taking developmental level into account compared to results based on a questionnaire. Conclusions Behaviour in individuals with CdLS should be evaluated taking genetic cause into account. Detailed interdisciplinary approaches are of clinical importance to inform tailored care and may eventually improve quality of life of patients and families. Show less
