Clonazepam repurposing in patients through conventional RCT and N-of-1 trials: an experimental strategy for orphan disease development.

Background: Clinical trials for rare disorders have unique challenges due to low prevalence, patient phenotype variability and high expectations. These challenges are highlighted by our study on clonazepam in patients, a common cause of intellectual disability. Previous studies on Arid1b-haploinsufficient mice showed positive effects of clonazepam on various cognitive aspects.

PROs for RARE: protocol for development of a core patient reported outcome set for individuals with genetic intellectual disability.

Introduction: Rare genetic neurodevelopmental disorders and intellectual disability (ID), collectively called genetic ID (GID), can profoundly impact daily functioning and overall well-being of affected individuals. To improve our understanding of the impact of GID and advancing both care and research, measuring relevant patient reported outcomes (PROs) is crucial. Currently, various PROs are measured for GID.

Do we care? Reporting of genetic diagnoses in multidisciplinary intellectual disability care: a retrospective chart review.

Background: Advances in understanding the etiology of intellectual disability (ID) has led to insights in potential (targeted) treatments and personalized care. Implications of ID on health are often complex and require a multidisciplinary approach. The aim was to investigate the reporting of genetic diagnoses in multidisciplinary ID care and to identify associated clinical and demographic factors.

Dementia in Rare Genetic Neurodevelopmental Disorders: A Systematic Literature Review.

Background And Objectives: Knowledge of young-onset Alzheimer disease in adults with Down syndrome has greatly improved clinical care. However, little is known about dementia in rare genetic neurodevelopmental disorders (RGNDs). In this review, a comprehensive overview is provided of reports on dementia and cognitive/adaptive trajectories in adults with RGNDs.

Navigating the outcome maze: a scoping review of outcomes and instruments in clinical trials in genetic neurodevelopmental disorders and intellectual disability.

Background: Individuals with genetic neurodevelopmental disorders (GNDs) or intellectual disability (ID) are often affected by complex neuropsychiatric comorbidities. Targeted treatments are increasingly available, but due to the heterogeneity of these patient populations, choosing a key outcome and corresponding outcome measurement instrument remains challenging.

Objectives: The aim of this scoping review was to describe the research on outcomes and instruments used in clinical trials in GNDs and ID.

Evaluation of 100 Dutch cases with 16p11.2 deletion and duplication syndromes; from clinical manifestations towards personalized treatment options.

The 16p11.2 deletion syndrome is a clinically heterogeneous disorder, characterized by developmental delay, intellectual disability, hyperphagia, obesity, macrocephaly and psychiatric problems. Cases with 16p11.

Corrigendum to "Effectiveness of L-serine supplementation in children with a GRIN2B loss-of-function mutation: Rationale and protocol for single patient (n-of-1) multiple cross-over trials" [Contemp. Clin. Trials Commun. 36 (2023)/ DOI: 10.1016/j.conctc.2023.101233].

[This corrects the article DOI: 10.1016/j.conctc.

Symptomatic creatine phosphokinase elevation in a Crohn's disease patient caused by upadacitinib.

We present a Crohn's disease patient receiving high dose upadacitinib treatment with elevated CPK levels and myopathy, and provide the reader with practical tips on stopping and restarting upadacitinib, emphasizing the need for adequate monitoring.

Effectiveness of L-serine supplementation in children with a loss-of-function mutation: Rationale and protocol for single patient (n-of-1) multiple cross-over trials.

Rationale: Loss-of-function (LoF) mutations in result in neurologic abnormalities due to -methyl-D-aspartate receptor (NMDAR) dysfunction. Affected persons present with various symptoms, including intellectual developmental disability (IDD), hypotonia, communication deficits, motor impairment, complex behavior, seizures, sleep disorders and gastrointestinal disturbance. Recently, experiments showed that D-serine mitigates function to GluN2B (mutation)-containing NMDARs.

Hearing loss and history of otolaryngological conditions in adults with microdeletion 22q11.2.

Previous studies have shown that the 22q11.2 microdeletion, associated with 22q11.2 deletion syndrome (22q11.

International consensus recommendations for the identification and treatment of tuberous sclerosis complex-associated neuropsychiatric disorders (TAND).

Background: Tuberous sclerosis complex (TSC) is associated with a wide range of physical manifestations for which international clinical recommendations for diagnosis and management have been established. TSC is, however, also associated with a wide range of TSC-Associated Neuropsychiatric Disorders (TAND) that are typically under-identified and under-treated yet associated with a profound burden of disease. The contemporary evidence base for the identification and treatment of TAND is much more limited and, to date, consensus recommendations for the diagnosis and management of TAND have also been limited and non-specific.

Intellectual and Behavioral Phenotypes of Smith-Magenis Syndrome: Comparisons between Individuals with a 17p11.2 Deletion and Pathogenic Variant.

Aim: Smith-Magenis syndrome (SMS) is a rare genetic neurodevelopmental disorder caused by a 17p11.2 deletion or pathogenic variant in the gene. SMS is associated with developmental delay, intellectual disability (ID), and major sleep and behavioral disturbances.

Development and Feasibility of the Self-Report Quantified Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders Checklist (TAND-SQ).

Background: Tuberous sclerosis complex-associated neuropsychiatric disorders (TAND) are often present but underidentified and undertreated in individuals with tuberous sclerosis complex (TSC). The clinician-completed TAND-Lifetime Checklist (TAND-L) was developed to address this identification and treatment gap. Stakeholder engagement identified the need for a TAND Checklist that can (1) be completed by caregivers or individuals with TSC and (2) quantify TAND difficulties.

Understanding the impact of tuberous sclerosis complex: development and validation of the TSC-PROM.

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.

Parkinsonism in Genetic Neurodevelopmental Disorders: A Systematic Review.

Background: With advances in clinical genetic testing, associations between genetic neurodevelopmental disorders and parkinsonism are increasingly recognized. In this review, we aimed to provide a comprehensive overview of reports on parkinsonism in genetic neurodevelopmental disorders and summarize findings related to genetic diagnosis, clinical features and proposed disease mechanisms.

Methods: A systematic literature review was conducted in PubMed and Embase on June 15, 2021.

Post-traumatic stress in adults with 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.2DS) is associated with an elevated genetic risk of several psychiatric disorders.

Personalized medicine for rare neurogenetic disorders: can we make it happen?

Rare neurogenetic disorders are collectively common, affecting 3% of the population, and often manifest with complex multiorgan comorbidity. With advances in genetic, -omics, and computational analysis, more children can be diagnosed and at an earlier age. Innovations in translational research facilitate the identification of treatment targets and development of disease-modifying drugs such as gene therapy, nutraceuticals, and drug repurposing.

Empowering Families Through Technology: A Mobile-Health Project to Reduce the TAND Identification and Treatment Gap (TANDem).

Introduction: Tuberous Sclerosis Complex (TSC) is a multi-system genetic disorder with various TSC-Associated Neuropsychiatric Disorders (TAND) that significantly impact the mental health and wellbeing of individuals with TSC and their caregivers. TAND represents the number one concern to families worldwide, yet is highly under-identified and under-treated. The clinician-administered TAND-Checklist (Lifetime version, TAND-L) has improved identification of TAND in clinical settings.

The research landscape of tuberous sclerosis complex-associated neuropsychiatric disorders (TAND)-a comprehensive scoping review.

Background: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) is an umbrella term for the behavioural, psychiatric, intellectual, academic, neuropsychological and psychosocial manifestations of TSC. Although TAND affects 90% of individuals with TSC during their lifetime, these manifestations are relatively under-assessed, under-treated and under-researched. We performed a comprehensive scoping review of all TAND research to date (a) to describe the existing TAND research landscape and (b) to identify knowledge gaps to guide future TAND research.

Ocular findings in 22q11.2 deletion syndrome: A systematic literature review and results of a Dutch multicenter study.

The 22q11.2 deletion syndrome (22q11.2DS) is a multisystem disorder with an estimated prevalence of 1:3000 live births.