Applying the Lessons of Tuberous Sclerosis: The 2015 Hower Award Lecture

Roach, E. Steve

doi:10.1016/j.pediatrneurol.2016.07.003

Cited by 50 publications

(33 citation statements)

References 95 publications

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“…Of interest, a phase 3 clinical trial showed efficacy in reducing seizure frequency in refractory epilepsy associated with TSC (French et al ., ). Clinical trials are currently ongoing with mTOR inhibitors in patients suffering TSC, ASD and PTEN‐related disorders (Roach, ; http://www.ClinicalTrials.org).…”

Section: Therapeutic Perspectivesmentioning

confidence: 99%

Neurobiological bases of autism–epilepsy comorbidity: a focus on excitation/inhibition imbalance

Bozzi

Provenzano

Casarosa

2017

Eur J of Neuroscience

205

156

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Autism spectrum disorders (ASD) and epilepsy are common neurological diseases of childhood, with an estimated incidence of approximately 0.5-1% of the worldwide population. Several genetic, neuroimaging and neuropathological studies clearly showed that both ASD and epilepsy have developmental origins and a substantial degree of heritability. Most importantly, ASD and epilepsy frequently coexist in the same individual, suggesting a common neurodevelopmental basis for these disorders. Genome-wide association studies recently allowed for the identification of a substantial number of genes involved in ASD and epilepsy, some of which are mutated in syndromes presenting both ASD and epilepsy clinical features. At the cellular level, both preclinical and clinical studies indicate that the different genetic causes of ASD and epilepsy may converge to perturb the excitation/inhibition (E/I) balance, due to the dysfunction of excitatory and inhibitory circuits in various brain regions. Metabolic and immune dysfunctions, as well as environmental causes also contribute to ASD pathogenesis. Thus, an E/I imbalance resulting from neurodevelopmental deficits of multiple origins might represent a common pathogenic mechanism for both diseases. Here, we will review the most significant studies supporting these hypotheses. A deeper understanding of the molecular and cellular determinants of autism-epilepsy comorbidity will pave the way to the development of novel therapeutic strategies.

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Section: Therapeutic Perspectivesmentioning

confidence: 99%

Neurobiological bases of autism–epilepsy comorbidity: a focus on excitation/inhibition imbalance

Bozzi

Provenzano

Casarosa

2017

Eur J of Neuroscience

205

156

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“…The most common cardiac finding of TSC is rhabdomyoma, which may be detected by ultrasonography in at least 50% of newborns between 20 and 30 weeks of gestation. Patients may be asymptomatic but may also present with severe heart failure or, owing to a compression of the cardiac conduction system, arrhythmia [1,2,18] . Rhabdomyomas in our patients did not produce any symptoms, and echocardiographic examination revealed no form of arrhythmia.…”

Section: Discussionmentioning

confidence: 99%

“…Thereafter, in 1880, Bourneville described the condition more in depth. Since then, the term TSC was used to describe the condition [1] . Mental retardation, convulsions, and adenoma sebaceum form the diagnostic triad of the condition.…”

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confidence: 99%

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Retrospective radiological and clinical of assessment 16 patients with Tuberous sclerosis

Güngör¹

2019

Haydarpasa Numune Med J

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Introduction: Tuberous sclerosis (TSC) is a multisystem, autosomal dominant disorder with a wide clinical spectrum. The aim of the present study was to review the clinical, radiological, and laboratory findings of our TSC cases in a retrospective manner and to compare them with the current literature. Methods: The clinical and radiological features of 16 patients diagnosed with TSC at Sütçü İmam University, Faculty of Medicine, Pediatric Neurology Outpatient Clinic were retrospectively assessed. Results: A total of 16 patients with a diagnosis of TSC were included in the study. The study included 9 (56.2%) male and 7 (43.7%) female patients. Of the 16 patients, 9 (56.2%) presented with convulsions, 4 (25%) with body rash, 2 (12.5%) with cardiac rhabdomyoma diagnosed at the newborn period, and 1 (6.25%) with perinatal asphyxia. Hypopigmented skin lesions were detected in all patients (100%). The most common finding on brain magnetic resonance imaging (MRI) was periventricular subependymal nodules (SNs) (n=12, 75%). In addition to the central nervous system and skin findings, 3 (18.7%) patients had cardiac involvement, and 1 (6.2%) patient had renal involvement. Three (18.7%) patients were detected with diffuse developmental delay, and 6 (37.5%) patients were detected with mental retardation. Discussion and Conclusion: In line with the current literature, convulsions, hypopigmented skin lesions, mental retardation, and SNs on brain MRI were the most common signs.

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“…Tubers growing in the brain are the main factors contributing to high morbidity and mortality in TSC. Brain involvement is often associated with the presence of epilepsy and TAND (Tuberous sclerosis Associated Neuropsychiatric Disorders) 3 . Clinical diagnosis of TSC is based upon identification of agreed and published major and minor diagnostic criteria 4,5 .…”

Section: Introductionmentioning

confidence: 99%

Mutational analysis of TSC1 and TSC2 genes in Tuberous Sclerosis Complex patients from Greece

Avgeris

Fostira

Vagena

et al. 2017

Sci Rep

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Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder causing benign tumors in the brain and other vital organs. The genes implicated in disease development are TSC1 and TSC2. Here, we have performed mutational analysis followed by a genotype-phenotype correlation study based on the clinical characteristics of the affected individuals. Twenty unrelated probands or families from Greece have been analyzed, of whom 13 had definite TSC, whereas another 7 had a possible TSC diagnosis. Using direct sequencing, we have identified pathogenic mutations in 13 patients/families (6 in TSC1 and 7 in TSC2), 5 of which were novel. The mutation identification rate for patients with definite TSC was 85%, but only 29% for the ones with a possible TSC diagnosis. Multiplex ligation-dependent probe amplification (MLPA) did not reveal any genomic rearrangements in TSC1 and TSC2 in the samples with no mutations identified. In general, TSC2 disease was more severe than TSC1, with more subependymal giant cell astrocytomas and angiomyolipomas, higher incidence of pharmacoresistant epileptic seizures, and more severe neuropsychiatric disorders. To our knowledge, this is the first comprehensive TSC1 and TSC2 mutational analysis carried out in TSC patients in Greece.

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Applying the Lessons of Tuberous Sclerosis: The 2015 Hower Award Lecture

Cited by 50 publications

References 95 publications

Neurobiological bases of autism–epilepsy comorbidity: a focus on excitation/inhibition imbalance

Neurobiological bases of autism–epilepsy comorbidity: a focus on excitation/inhibition imbalance

Retrospective radiological and clinical of assessment 16 patients with Tuberous sclerosis

Mutational analysis of TSC1 and TSC2 genes in Tuberous Sclerosis Complex patients from Greece

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