Publications by authors named "Iris Overwater"
Background: Tuberous sclerosis complex (TSC) is a highly variable condition and its clinical features cannot reliably be predicted from the genotype. Counselling of parents of a child with TSC is challenging because of the variability of the condition and the changing outlook due to new treatment options. This study explored current counselling strategies in TSC in the Netherlands, with the aim of developing a recommendation for counselling.
View Article and Find Full Text PDFUp to 90% of patients with tuberous sclerosis complex (TSC) have epilepsy, and in over half of patients seizure control cannot be achieved by regular antiepileptic drugs. The underlying problem is mTOR hyperactivation due to loss of function of the TSC proteins. Treatment with everolimus, an mTOR inhibitor, has been shown to be of great benefit to TSC patients, both in reducing tumor growth and as a treatment for intractable epilepsy.
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- The study aimed to explore if everolimus, a medication, could help improve intellectual disability, autism, and other neuropsychological issues in children with tuberous sclerosis complex (TSC).
- In a year-long trial involving 60 children aged 4-17 with TSC and low IQ, the results showed no improvement in IQ or other secondary measures like autism and behavioral issues after taking everolimus compared to a placebo.
- The findings concluded that everolimus does not help cognitive or behavioral functioning in children with TSC, indicating it should not be used for these purposes in this age group.
Tuberous Sclerosis Complex (TSC) is characterized by a high prevalence of autism spectrum disorders (ASD). Little is known about the relation between cortical dysplasia and ASD severity in TSC. We assessed ASD severity (using the Autism Diagnostic Observation Scale), tuber and radial migration line (RML) count and location, and cognitive functioning in 52 children with TSC and performed regression and mediation analyses.
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- RASopathies are genetic disorders linked to mutations in genes related to the RAS-ERK signaling pathway, leading to a range of intellectual disabilities, but their underlying mechanisms are not well understood.
- Costello syndrome, a specific type of RASopathy from HRAS mutations, was studied in HRas mice, revealing increased ERK signaling, neuronal growth, and learning difficulties, while other signaling changes seen in other RASopathies were not present.
- Treatments like lovastatin didn't improve cognitive issues in HRas mice, but a MEK inhibitor helped with some signaling problems without fixing the cognitive deficits, suggesting that different RASopathies may need tailored therapeutic approaches.
Objective: To investigate whether mammalian target of rapamycin complex 1 (mTORC1) inhibitors could reduce seizure frequency in children with tuberous sclerosis complex (TSC).
Methods: Due to slow inclusion rate, target inclusion of 30 children was not reached. Twenty-three children with TSC and intractable epilepsy (age 1.
Structural brain malformations associated with Tuberous Sclerosis Complex (TSC) are related to the severity of the clinical symptoms and can be visualized by magnetic resonance imaging (MRI). Tuberous Sclerosis Complex is caused by inactivating TSC1 or TSC2 mutations. We investigated associations between TSC brain pathology and different inactivating TSC1 and TSC2 variants, and examined the potential prognostic value of subdivision of TSC2 variants based on their predicted effects on TSC2 expression.
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- Understanding the causes of intellectual disabilities in genetic disorders can lead to better treatments, but the transition from promising research to actual medical therapies is not well-established.* -
- A review of clinical trials found 169 reports on 80 treatments for 32 genetic disorders, of which only 2 therapies are recognized as effective treatments today.* -
- The study highlights that many trials have small sample sizes and low-quality designs, with poor alignment between reported outcomes and original trial registrations, limiting their clinical impact.*
Objective: To describe treatment and outcome of epilepsy in children with tuberous sclerosis complex (TSC).
Methods: Seventy-one children with TSC and epilepsy treated at the ENCORE TSC Expertise Center between 1988 and 2014 were included. Patient characteristics and duration and effectiveness of antiepileptic treatments were extracted from our clinical database.
Objective: Seizure development in tuberous sclerosis complex (TSC) correlates with the presence of specific lesions called cortical tubers. Moreover, heterozygous TSC animal models do not show gross brain pathology and are seizure-free, suggesting that such pathology is a prerequisite for the development of epilepsy. However, cells within TSC lesions show increased activity of the target of rapamycin complex 1 (TORC1) pathway, and recent studies have implicated this pathway in non-TSC-related animal models of epilepsy and neuronal excitability.
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