Diagnosis, monitoring and treatment of tuberous sclerosis complex: A South African consensus response to international guidelines

Abstract

Gomez identified that patients with TSC had a wide range of physical manifestations across almost all organ systems, including the brain, skin, heart, eyes, kidneys and lungs, and that multi-system involvement was highly variable between patients. He also recognised (in contrast to Corresponding author: P J de Vries (petrus.devries@uct.ac.za)Tuberous sclerosis complex (TSC) is a genetic disorder with multi-system manifestations and a high burden of disease. In 2013, an international panel of TSC experts revised the guidelines for the diagnosis, surveillance and treatment of the disorder. In South Africa (SA), a local multidisciplinary group of healthcare professionals and TSC researchers reviewed the international guidelines to generate an SA consensus clinical update on the identification, diagnosis, treatment and lifelong monitoring of individuals who live with TSC. We strongly endorse dissemination and use of the international guidelines for the assessment, monitoring and treatment of TSC. In addition, we strongly support access to genetic testing and to mTOR (mammalian target of rapamycin) inhibitors to treat subependymal giant cell astrocytomas not amenable to surgery and renal angiomyolipomas larger than 3 cm, and as adjunctive treatment for refractory focal seizures. We await with interest results from mTOR inhibitor trials of skin and TSC-associated neuropsychiatric disorders (TAND). With regard to training, we recommend the inclusion of TSC in undergraduate and postgraduate medical and health sciences curricula, and the promotion of other continuing professional development events to raise awareness about TSC. We also support the development of a TSC user/carer/parent organisation to provide an informal support network for families across SA. We acknowledge that some progress has been made in recent years in SA, but much remains to be done. We hope that this SA consensus clinical update based on the international guidelines will make a positive contribution to increase knowledge and improve clinical care for all patients who live with TSC in SA, and their families.

Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations

“…The previous guidelines 8 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 2012 [179][180][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.…”

Beyond the Guidelines: How We Can Improve Healthcare for People With Tuberous Sclerosis Complex Around the World

“…Devries et al documented the approach taken in South Africa to generate a country-specific consensus statement on the management of TSC. 19 Other country-level TSC organizations or groups of interested health professionals could adopt a similar approach. Projects to address country-specific challenges, such as working with private and public insurers to fund imaging and treatments.…”

Meeting the complex needs of individuals with rare genetic disorders in South Africa – lessons from tuberous sclerosis complex

“…[3,5,6] So, what about TSC? TSC is a rare genetic disorder, associated with very obvious 'chronic multi-morbidity' (see de Vries et al [7] in this issue of SAMJ). The majority of individuals with TSC are diagnosed in the first few years of life, but some are not diagnosed until adolescence or adulthood.…”

“…However, conscious that there were well-regarded international consensus guidelines for the diagnosis, monitoring and treatment of TSC, [14,15] we set out to draft a clinical update summarising an evidence-based and international consensus approach to the assessment and treatment of TSC. [7] We realised that the majority of people with TSC in SA are probably cared for by general practitioners, and only a few by specialists. For that reason, we were keen to generate a broad and general document that we hoped would assist general practitioners, specialists, families and individuals with TSC.…”

“…The disorder remained relatively obscure until the early 2000s, when the molecular mechanisms of TSC were identified, showing that the two proteins directly affected, TSC1 and TSC2, are key regulators in a funda mental intracellular signalling pathway, the mTOR (mammalian target of rapamycin) pathway. [7] This pathophysiological discovery led remarkably rapidly to the identification of molecularly targeted treatments for TSC -medications that specifically and directly inhibit mTOR to reduce the overactivation resulting from deficits in TSC1 or TSC2 proteins. The mTOR proteins have since also been shown to be involved in neurofibromatosis type 1 and fragile X syndrome (two other rare genetic disorders), in response to cannabis (a rather common pheno menon), and in longevity.…”