Tüberoz Skleroz Kompleksi
Özet
Tüberoz skleroz kompleksi (TSK), TSC1 veya TSC2 gen mutasyonları sonucu gelişen ve mTOR yolunun aşırı aktivasyonuna yol açan multisistemik, otozomal dominant kalıtılan nörokutanöz bir hastalıktır. Merkezi sinir sistemi tutulumu, epilepsi ve nöropsikiyatrik bozukluklar, dermatolojik belirtiler, kardiyak rabdomyomlar ve renal anjiyomiyolipomlar hastalığın temel klinik bulgularını oluşturur. Güncel tedavide mTOR inhibitörleri (sirolimus, everolimus), özellikle SEGA, renal anjiyomiyolipom, LAM ve dirençli epilepsi yönetimi için kritik bir yere sahiptir. Tanı, 2012 yılı kriterlerine dayanarak klinik bulgular ve genetik analiz ile konulur.
Tuberous Sclerosis Complex (TSC) is a multisystem, autosomal dominant neurocutaneous disorder caused by mutations in the TSC1 or TSC2 genes, leading to constitutive activation of the mTOR pathway. Central nervous system involvement, including epilepsy and neuropsychiatric disorders, alongside dermatological manifestations, cardiac rhabdomyomas, and renal angiomyolipomas, constitute the primary clinical features. mTOR inhibitors (sirolimus, everolimus) have become pivotal in current therapeutic strategies, particularly for managing SEGA, renal angiomyolipomas, LAM, and refractory epilepsy. Diagnosis is confirmed through the 2012 clinical criteria and genetic analysis.
Referanslar
Randle SC. Tuberous Sclerosis Complex: A Review. Pediatr Ann 2017;1;46:166-171.
Kaneda MW, Uemura M , Fujita K et al. Tuberous sclerosis complex: Recent advances in manifestations and therapy. International Journal of Urology 2017; 24: 681-691.
Portocarrero LKL, Quental KN, Samorano LP et al. Tuberous sclerosis complex: review based on new diagnostic criteria. An Bras Dermatol. 2018 ; 93: 323–331.
Islam MP, Roach ES Tuberous sclerosis complex. Handb Clin Neurol 2015;132:97-109.
Peron A, Northrup H. Tuberous sclerosis complex. Am J Med Genet.2018 ;178:274-277.
Samueli S, Abraham K , Dressler A et al. Tuberous Sclerosis Complex: new criteria for diagnostic work –up and management .Wien Klin Wochenschr 2015 ;127:619-30.
Curatolo P, Moavero R, J de Vries P. Neurological and neuropsychiatric aspects of tuberous sclerosis complex . Lancet Neurol.2015 ; 14; 733-745.
Curatolo P, Maria BL. Tuberous sclerosis . Handb Clin Neurol 2013;111:323-331.
Waele DL, Lagae L, Mekahli D. Tuberous sclerosis complex:the past and the future . Pediatr Nephrol.2015 ;30:1771-80.
Uçar H,Altunbaşak Ş. Tüberoz Skleroz Kompleks Hastalığı (Bourneville Hastalığı).Yalaz K, editör.Temel Gelişimsel Çoçuk Nörolojisi. 2.Baskı.2018. p.147-159
Öztürk S, Samur MB, Canpolat M. Tüberoz skleroz kompleksi. Çarman KB, editör. Nörokütanöz Hastalıklar. 1. Baskı. Ankara: Türkiye Klinikleri; 2021. p.114-31.
Franz DN, Belousova E, Sparagana S, et al. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1):a multicentre randomised, placebo-controlled phase3 trial. Lancet 2013;12;381:125-32
Lu DS, Karas PJ, Krueger DA, Weiner HL Central nervous system manifestations of tuberous sclerosis complex. Am J Med Genet 2018;178:291-298.
Franz DN, Leonard J, Tudor C, et al. Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann of Neurol 2006;59:490-498.
Krueger DA, Care MM, Holland K, et al. Everolimus for Subependymal Giant-Cell Astrocytomas in Tuberous Sclerosis. N Engl J Med 2010; 363:1801-1811.
Franz DN, Belousova E, Sparagana S, et al. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1):a multicentre randomised, placebo-controlled phase3 trial. Lancet 2013;12;381:125-32
Orduna P. Sirolimus as an alternative to surgical resection of pediatric tuberous sclerosis complex-associated bilateral subependymal gıant cell astrocytomas :An affordable optıon for patients from low mıddle ıncome countries. Neuro Oncol. 2020 ; 22( 3): iii381
Curatolo P, Moavero R, Scheppingen J, Aronica E. mTor dysregulation and tuberous sclerosis-related epilepsy . Expert Rev Neurother 2018;18:185-201.
Zhang K, Hu WH, Zhang C, Meng FG, Chen N, Zhang JG. Predictors of seizure freedom after surgical management of tuberous sclerosis complex: a systematic review and meta-analysis. Epilepsy Res 2013; 105: 377 -383.
Krsek P, Jahodova A, Kyncl M, et al. Predictors of seizure-free outcome after epilepsy surgery for pediatric tuberous sclerosis complex. Epilepsia 2013; 54: 1913–21.
Kossoff EH, Thiele EA, Pfeifer HH, McGrogan JR, Freeman JM. Tuberous sclerosis complex and the ketogenic diet. Epilepsia 2005; 46: 1684–86.
Coppola G, Klepper J, Ammendola E, et al. The eff ects of the ketogenic diet in refractory partial seizures with reference to tuberous sclerosis. Eur J Paediatr Neurol 2006; 10: 148–51.
Randell E, McNamara R, Davies DM, et al.The use of everolimus in the treatment of neurocognitive problems in tuberous Sclerosis (TRON) :Study protocol for a randomised controlled trial .Trials (2016) 17:398
Northrup H, .Krueger DA. Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference Pediatric Neurology 2013,49:243-254.
Vries PJ, Whittemore VH, Leclezio L ,Byars AW , Dunn D, Ess KC et al.Tuberous sclerosis associated neuropsychiatric disorders (TAND) and the TAND Checklist. Pediatr Neurol 2015;52:25-35.
Pulsifer MB, Winterkorn EB, Thiele EA. Psychological profile of adults with tuberous sclerosis complex. Epilepsy & Behavior 2007;10: 402-406.
Shepherd M.B, Stephenson BP. Seizures and intellectual disability associated with tuberous sclerosis complex in the west of Scotland. DMCN 1992;34 : 766-774.
Sato A.mTOR, a Potential Target to Treat Autism Spectrum Disorder. CNS Neurol Disord Drug Targets. 2016; 15: 533–543.
Cardis MA , Carver CM, Klotz D. Cutaneous manifestations of tuberous sclerosis complex and the paediatrician’s role . Arch Dis Child 2017;102:858-863.
Teng JMC, Cowen EW , Wataya-Kaneda M, Gosnell ES, Witman PM, Hebert AA et al. Dermatologic and dental aspects of the 2012 İnternational Tuberous Sclerosis Complex Consensus Statements . JAMA Dermatol 2014 ;150:1095-101
Jacks SK, Witman PM. Tuberous Sclerosis Complex: An Update for Dermatologists. Pediatr Dermatol. 2015 ;32:563-70.
Cinar SL, Kartal D, Bayram AK, Canpolat M, Borlu M, Ferahbas A, Per H. Topical sirolimus for the treatment of angiofibromas in tuberous sclerosis. Indian J Dermatol Venereol Leprol. 2017;83(1):27-32.
Hishitani T, Hoshino K, Ogawa K et al.. Rapid enlargement of cardiac rhabdomyoma during corticotropin therapy for infantile spasms. Can J Cardiol. 1997 Jan;13(1):72-4.
Goyer I, Dahdah N, Major P . Use of mTOR Inhibitor Everolimus in Three Neonates for Treatment of Tumors Associated With Tuberous Sclerosis Complex Pediatric Neurology 2015;52 450-453.
ChenV, Wang Y, Zhang M et al. Sirolimus Can İncrease the Disappearance Rate of Cardiac Rhabdomyomas Associated with Tuberous Sclerosis: A Prospective Cohort and Self-Controlled Case Series Study. The Journal of Pediatrics 2021; 150-155.
Sugalska M, Tomik A, Jóźwiak S, Werner B Treatment of Cardiac Rhabdomyomas with mTOR İnhibitors in Children with Tuberous Sclerosis Complex—A Systematic Review Int. J. Environ. Res. Public Health 2021;18:4907.
Luo C, Zhang Y, Zhang M, et al.Everolimus versus sirolimus for angiomyolipoma associated with tuberous sclerosis complex: a multi-institutional retrospective study in China Orphanet J Rare Dis (2021) 16:299.
Bissler JJ , Kingswood JC, Radzikowska E, et al. Everolimus long-term use in patients with tuberous sclerosis complex: Four-year update of the EXIST-2 study. PLOS ONE 12(8): e0180939
Raab C, Gilligan LA, Trout TA, Krueger DA, Franz DN, Zhang B. mTOR İnhibitor Therapy for Tuberous Sclerosis Complex: Longitudinal Study of Muscle Mass Determined by Abdominal Cross-sectional İmaging with CT and MRI. Radiol Imaging Cancer. 2020 ; 2(5): e190091.
Agricola K, Stires G, Krueger DA, Franz ND, ,Ritter DM Diabetes in İndividuals With Tuberous Sclerosis Complex Treated With mTOR İnhibitors. Pediatric Neurology, 2021;120: 7-10.
Wiemer-Kruel A, Nabbout R, Fan PC, Falco MLR, Polster T,Curatolo P, et al. Outcomes among adult patients with tuberous sclerosis complex (TSC)-associated treatment-refractory seizures treated with adjunctive everolimus: final analysis of the Exist-3 study.Epilepsia. 2018; 59 (S5-S5)
Canpolat M, Per H, Gumus H, Yikilmaz A, Unal E, Patiroglu T, Cinar L, Kurtsoy A, Kumandas S. Rapamycin has a beneficial effect on controlling epilepsy in children with tuberous sclerosis complex: results of 7 children from a cohort of 86. Childs Nerv Syst. 2014 Feb;30(2):227-40.
Canpolat M, Gumus H, Kumandas S, Coskun A, Per H. The use of rapamycin in patients with tuberous sclerosis complex: Long-term results. Epilepsy Behav. 2018 Nov;88:357-364.
