Tuberous sclerosis complex (TSC) : expert recommendations for provision of coordinated care

Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem genetic disorder characterized by benign tumors in multiple organs, including the skin, brain, kidneys, and lungs and occasional malignant tumors. Hamartomas in the brain, retina, and sometimes other organs also occur (1–3). The e...

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Hauptverfasser: Annear, N.M.P, Appleton, R.E, Bassi, Z, Bhatt, R, Bolton, P.F, Crawford, P, Crowe, A, Tossi, M, Elmslie, F, Finlay, E, Gale, D.P, Henderson, A, Jones, E.A, Johnson, S.R, Joss, S, Kerecuk, L, Lipkin, G, Morrison, P.J, O'Callaghan, F.J, Cadwgan, J, Ong, A.C.M, Sampson, J.R, Shepherd, C, Kingswood, J.C
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Zusammenfassung:Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem genetic disorder characterized by benign tumors in multiple organs, including the skin, brain, kidneys, and lungs and occasional malignant tumors. Hamartomas in the brain, retina, and sometimes other organs also occur (1–3). The estimated prevalence is 1:600–1:10,000 live births in the general population (4–6). Patients present at different ages with different manifestations, and varying degrees of organ involvement (Figure 1). CNS manifestations of TSC mainly present in childhood, affect around 85% of patients (8), frequently resulting in epilepsy refractory to treatment, intellectual impairment, autistic spectrum disorder, attention deficit hyperactivity disorder, and behavioral problems (1–3). Renal angiomyolipomas (AMLs) occur in ~80% of patients (9); kidney disease is the leading cause of death in adults with TSC (10). TSC is complex and highly varied (Figure 1) necessitating careful coordination of care, which is lacking for most patients in the UK. Some TSC manifestations are rarer; e.g., subependymal giant cell astrocytoma (SEGA) occurs in around 20–24% of patients (11, 12) (Figure 2). The major unsolved problem in TSC is refractory epilepsy and TSC-associated neuropsychiatric disorders (TAND); of which preliminary evidence suggests refractory epilepsy is a major cause (13–15). TSC, like other complex rare diseases, is a major burden to patients, families and healthcare systems. Optimizing care will alleviate some of this while waiting for medical research to deliver a cure. Classically, a clinical diagnosis of TSC is made by identifying major and minor features (Table 1) (1, 16). With wider availability of genetic testing, identification of pathogenic mutations in TSC1 or TSC2 is now sufficient to establish a diagnosis, regardless of the presence of clinical features (1, 16), and is particularly useful in confirming a suspected diagnosis, as many clinical TSC manifestations are infrequent in young patients (1, 16). The approval of the mTORC1 inhibitor—everolimus—for the treatment of AMLs, SEGA, and refractory epilepsy represents a significant advance in the potential management of the disease (17–19). Whilst not licensed in Europe, the Federal Drugs Agency (FDA) have also approved sirolimus for use in pulmonary lymphangioleiomyomatosis (LAM) (18). Refractory seizures adversely affect early development (20). Furthermore, appropriate early treatment of infantile spasms with vigaba
DOI:10.3389/fneur.2019.01116