Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference

Pediatric Neurology, Journal Year: 2013, Volume and Issue: 49(4), P. 243 - 254

Published: Sept. 20, 2013

BackgroundTuberous sclerosis complex is highly variable in clinical presentation and findings. Disease manifestations continue to develop over the lifetime of an affected individual. Accurate diagnosis fundamental implementation appropriate medical surveillance treatment. Although significant advances have been made past 15 years understanding treatment tuberous complex, current diagnostic criteria not critically evaluated or updated since last consensus conference 1998.MethodsThe 2012 International Tuberous Sclerosis Complex Consensus Group, comprising 79 specialists from 14 countries, was organized into 12 subcommittees, each led by a clinician with advanced expertise relevant subspecialty. Each subcommittee focused on specific disease area important implications charged reviewing prevalence specificity disease-associated findings their impact suspecting confirming complex.ResultsClinical features be principal means diagnosis. Key changes compared 1998 are new inclusion genetic testing results reducing classes three (possible, probable, definite) two definite). Additional minor criterion were for additional clarification simplification.ConclusionsThe Diagnostic Criteria provide current, using best available evidence establish individuals.

Language: Английский

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Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial

The Lancet, Journal Year: 2013, Volume and Issue: 381(9869), P. 817 - 824

Published: Jan. 11, 2013

Language: Английский

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Tuberous Sclerosis Complex Surveillance and Management: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference

Pediatric Neurology, Journal Year: 2013, Volume and Issue: 49(4), P. 255 - 265

Published: Sept. 19, 2013

Tuberous sclerosis complex is a genetic disorder affecting every organ system, but disease manifestations vary significantly among affected individuals. The diverse and varied presentations progression can be life-threatening with significant impact on cost quality of life. Current surveillance management practices are highly variable region country, reflective the fact that last consensus recommendations occurred in 1998 an updated, comprehensive standard lacking incorporates latest scientific evidence current best clinical practices.The 2012 International Sclerosis Complex Consensus Group, comprising 79 specialists from 14 countries, was organized into 12 separate subcommittees, each led by clinician advanced expertise tuberous relevant medical subspecialty. Each subcommittee focused specific area important implications charged formulating key questions to address within its focus area, reviewing literature, evaluating strength data, providing recommendation accordingly.The updated for summarized here. entire lifespan patient, infancy adulthood, including both individuals where diagnosis newly made as well already established.The Recommendations provide evidence-based, standardized approach optimal care provided complex.

Language: Английский

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The Neurology of mTOR

Neuron, Journal Year: 2014, Volume and Issue: 84(2), P. 275 - 291

Published: Oct. 1, 2014

Language: Английский

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The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes

Acta Neuropathologica, Journal Year: 2010, Volume and Issue: 119(6), P. 755 - 770

Published: March 2, 2010

Autism is characterized by a broad spectrum of clinical manifestations including qualitative impairments in social interactions and communication, repetitive stereotyped patterns behavior. Abnormal acceleration brain growth early childhood, signs slower neurons, minicolumn developmental abnormalities suggest multiregional alterations. The aim this study was to detect the focal defects identify regions that are prone alterations autism. Formalin-fixed hemispheres 13 autistic (4–60 years age) 14 age-matched control subjects were embedded celloidin cut into 200-μm-thick coronal sections, which stained with cresyl violet used for neuropathological evaluation. Thickening subependymal cell layer two brains nodular dysplasia one indicative active neurogenesis children. Subcortical, periventricular, hippocampal cerebellar heterotopias detected four (31%) reflect abnormal neuronal migration. Multifocal cerebral resulted local distortion cytoarchitecture neocortex (31%), entorhinal cortex (15%), cornu Ammonis dentate gyrus brains. Cerebellar flocculonodular six (46%), vermis case, hypoplasia subject indicate failure development 62% subjects. Detection only changes 12 examined (92%) reflects dysregulation neurogenesis, migration maturation autism, may contribute heterogeneity phenotype.

Language: Английский

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Tuberous sclerosis complex: Advances in diagnosis, genetics, and management

Journal of the American Academy of Dermatology, Journal Year: 2007, Volume and Issue: 57(2), P. 189 - 202

Published: July 17, 2007

Language: Английский

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A Synaptic Perspective of Fragile X Syndrome and Autism Spectrum Disorders

Neuron, Journal Year: 2019, Volume and Issue: 101(6), P. 1070 - 1088

Published: March 1, 2019

Language: Английский

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Molecular logic of mTORC1 signalling as a metabolic rheostat

Nature Metabolism, Journal Year: 2019, Volume and Issue: 1(3), P. 321 - 333

Published: March 4, 2019

Language: Английский

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Mosaic and Intronic Mutations in TSC1/TSC2 Explain the Majority of TSC Patients with No Mutation Identified by Conventional Testing

PLoS Genetics, Journal Year: 2015, Volume and Issue: 11(11), P. e1005637 - e1005637

Published: Nov. 5, 2015

Tuberous sclerosis complex (TSC) is an autosomal dominant tumor suppressor gene syndrome due to germline mutations in either TSC1 or TSC2. 10–15% of TSC individuals have no mutation identified (NMI) after thorough conventional molecular diagnostic assessment. 53 subjects who were NMI studied using next generation sequencing search for these genes. Blood/saliva DNA including parental samples available from all subjects, and skin biopsy was six subjects. We 45 (85%). Mosaicism observed the majority (26 45, 58%), intronic also unusually common, seen 18 (40%). Seventeen (38%) at allele frequency < 5%, five 1%, two biopsies only, not appreciable blood saliva DNA. These findings illuminate extent mosaicism TSC, indicate importance full coverage detection, show that analysis TSC-related tumors can increase detection rate, it likely a third exists, enable provision genetic counseling substantial population are currently NMI.

Language: Английский

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mTOR inhibitors in cancer therapy

F1000Research, Journal Year: 2016, Volume and Issue: 5, P. 2078 - 2078

Published: Aug. 25, 2016

The mammalian target of rapamycin, mTOR, plays key roles in cell growth and proliferation, acting at the catalytic subunit two protein kinase complexes: mTOR complexes 1 2 (mTORC1/2). mTORC1 signaling is switched on by several oncogenic pathways accordingly hyperactive majority cancers. Inhibiting has therefore attracted great attention as an anti-cancer therapy. However, progress using inhibitors therapeutic agents oncology been limited a number factors, including fact that classic inhibitor, inhibits only some effects mTOR; existence feedback loops; crucial importance normal physiology.

Language: Английский

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