Clinical Study
Managing tuberous sclerosis in the Asia-Pacific region: Refining practice and the role of targeted therapy

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Abstract

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder, with heterogeneous manifestations that pose major diagnostic and management challenges and incur considerable chronic disease burden on patients, their caregivers and healthcare systems. This survey of clinical practice in the Asia-Pacific region highlights priorities for improving TSC management in the region. The prevalence of TSC in non-Caucasians is uncertain and more data are needed to assess its impact and health-economic burden. There are unmet needs for access to genetic testing and earlier diagnosis and intervention. TSC management is multidisciplinary and largely based on experience, backed by international guidelines; however, physicians in the Asia-Pacific region feel isolated and lack local or regional guidance and support structures to implement best-practice. Raising awareness of TSC and increasing trans-regional collaboration are particular priorities. Understanding of TSC pathophysiology has enabled the development of targeted therapies. Encouraging data indicate that mammalian target of rapamycin (mTOR) inhibitors can ameliorate TSC-related lesions and may potentially change the treatment paradigm. Ultimately, improving outcomes for TSC patients in the region requires greater collaboration and a holistic, patient-focused, continuum of care that is maintained through the transition from pediatric to adult care.

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.

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