Clinical StudyManaging tuberous sclerosis in the Asia-Pacific region: Refining practice and the role of targeted therapy
Section snippets
Pathophysiology
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder with heterogeneous manifestations that affect multiple organs and systems. The classic clinical presentation includes epilepsy, skin lesions and intellectual impairment [1]; however, only 29% of TSC patients have all these symptoms and 6% have none of them [2].
TSC results from mutations in TSC1, which encodes hamartin, or TSC2, encoding tuberin [1]. The hamartin-tuberin heterodimer stabilizes tuberin, which in turn
Refining TSC management: Priorities and process
In this new era of targeted therapies, optimizing outcomes for TSC patients in the Asia-Pacific region becomes an increasing priority. However, this cannot be achieved without greater regional awareness of TSC and a better understanding of the challenges confronting clinicians; they especially need information and guidance to help bridge gaps between the latest evidence and everyday practice. Improving TSC management in the Asia-Pacific region also requires concerted trans-regional
Epidemiology
Clinicians in Asia-Pacific countries and regions generally perceive TSC to be rare; however, there is little information on its regional prevalence or trends. Of the seven countries represented, only Taiwan has published national data, with reported prevalence of 1.05/100,000 [39].
Awareness and resources
Physicians in Asia-Pacific are hampered by lack of awareness and under-diagnosis of TSC, particularly among non-specialist physicians. This is compounded by a lack of coherent structures and support for managing TSC.
Challenges and opportunities
Our survey provides important insights into current TSC management practice in Asia-Pacific, and serves as a benchmark to gauge progress. We acknowledge that these findings represent the practice and subjective views of a small, non-random, sample of clinicians, mostly from urban tertiary hospitals and with special interest in TSC. Therefore, these findings may not entirely typify each country or region. Nevertheless, our survey does represent real-life practice in managing a broad
Conflicts of Interest/Disclosures
The authors were members of an advisory board supported by an unrestricted educational grant from Novartis, and received honoraria from Novartis for this service. Novartis provided feedback on the survey but had no involvement in data collection, analysis, or presentation. Novartis reviewed manuscript drafts and supported the decision to publish; however, the authors had complete independence in writing and approving the paper.
Acknowledgements
The Asia-Pacific South Africa Tuberous Sclerosis Advisory Board was supported by Novartis. Dr David Neil, UBM Medica Asia Pte. Ltd., provided editorial support, which was funded by Novartis.
References (40)
- et al.
Tuberous sclerosis complex: advances in diagnosis, genetics, and management
J Am Acad Dermatol
(2007) - et al.
Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs
Am J Hum Genet
(2001) - et al.
Antiepileptic treatment before the onset of seizures reduces epilepsy severity and risk of mental retardation in infants with tuberous sclerosis complex
Eur J Paediatr Neurol
(2011) - et al.
Tuberous sclerosis
Lancet
(2008) - et al.
FKBP12 binds the inositol 1,4,5-trisphosphate receptor at leucine-proline (1400–1401) and anchors calcineurin to this FK506-like domain
J Biol Chem
(1997) - et al.
TOR signaling in growth and metabolism
Cell
(2006) Tuberous sclerosis
Eur J Hum Genet
(2006)- et al.
The tuberous sclerosis complex
Ann N Y Acad Sci
(2010) Mammalian target of rapamycin (mTOR) inhibition as a potential antiepileptogenic therapy: from tuberous sclerosis to common acquired epilepsies
Epilepsia
(2010)- et al.
Everolimus for subpendymal giant-cell astrocytomas in tuberous sclerosis
N Engl J Med
(2010)
Everolimus: an mTOR inhibitor for the treatment of tuberous sclerosis
Expert Rev Anticancer Ther
The tuberous sclerosis complex
N Engl J Med
Molecular and clinical analyses of 84 patients with tuberous sclerosis complex
BMC Med Genet
Tuberous sclerosis complex: diagnostic challenges, presenting symptoms, and commonly missed signs
Pediatrics
Burden of disease and unmet needs in tuberous sclerosis complex with neurological manifestations: a systematic review
Curr Med Res Opin
Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria
J Child Neurol
Tuberous sclerosis: epidemiology, genetics and progress towards treatment
Neuroepidemiology
Tuberous sclerosis consensus conference: recommendations for diagnostic evaluation. National tuberous sclerosis association
J Child Neurol
An Australian tuberous sclerosis cohort: are surveillance guidelines being met?
J Paediatr Child Health
The natural history of epilepsy in tuberous sclerosis complex
Epilepsia
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2021, Pediatric NeurologyCitation Excerpt :The previous guidelines8 have been translated into 17 languages, and in Portugal these were accepted as care standards for TSC and formally adopted by the National Ministry of Health. Several additional international groups have published their approach to implementing the previous guidelines from 2012179-181; these articles may serve as manuals for regions of similar size, economies, and/or health systems. Local medical providers and specialists may also need to adapt specific recommendations in such circumstances as best as they are able while continuing efforts to remedy and overcome these barriers for the optimal treatment of their patients.
Persistent organic pollutants (POPs) in deep-sea sediments of the tropical western Pacific Ocean
2021, ChemosphereCitation Excerpt :PAHs have also been found in the atmosphere and surface water (Wu et al., 2017), PCBs and PBDEs have been found in sediments (Dasgupta et al., 2018; Zhang et al., 2020), and PCBs and DDTs have even been found in the fatty tissues of sea turtles (Clukey et al., 2018). The Asia-Pacific region has the largest human population and highest rates of development of the Pacific coasts, making it an area of intense human activity (Lawson et al., 2019). Many chemical by-products from industrial and agricultural activities are constantly released into the ocean from this region (Lawson et al., 2019; Tanabe, 2007).
Novel TSC1 and TSC2 gene mutations in Chinese patients with tuberous sclerosis complex
2017, Clinical Neurology and NeurosurgeryCitation Excerpt :Eleven unrelated Chinese TSC patients were investigated in the present study. It has been reported that characteristic skin lesions such as hypomelanotic macules, angiofibromas, and shagreen patches, and central nervous system features such as the epilepsy, cortical tubers, and subependymal nodules are observed in about 80%–90% of TSC patients [4,11–13]. Similarly, skin lesions and the central nervous system features were the most common symptoms of the 11 patients examined in the present study.
Complete excision of a rare case of subependymal giant cell astrocytoma (SEGA) in tuberous sclerosis complex
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