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Evaluation of Tuberous Sclerosis Complex Patients

Yıl 2020, Cilt: 4 Sayı: 1, 82 - 87, 02.03.2020

Zeynep Selen Karalök Alev Güven Hüsniye Altan Zeynep Öztürk Nesrin Ceylan Esra Gürkaş

https://doi.org/10.30565/medalanya.584167

Öz

Aim: Tuberous sclerosis complex (TSC) is a multisystem genetic, autosomal-dominant disorder predisposing to multiple organ manifestations. The aim of this study is to determine TSC the frequency of findings including diagnostic and non-diagnostic criteria.

Patients and Metod: Thirty-five patients diagnosed with tuberous sclerosis complex were examined retrospectively. The diagnosis of the patients were evaluated according to the diagnostic criteria of TSC that were updated in 2012. As non-diagnostic criteria, we reviewed epilepsy, drug-resistant epilepsy, electroencephalography (EEG) types (focal, diffuse-multifocal and hypsarrhythmia) and TAND (TSC-associated neuropsychiatric disorders) (intellectual disability and/or autism and learning disability).

Results: Twenty-one cases (60%) presented with seizures, 9 cases (26%) with hypopigmented patches and 5 cases (14%) with cardiac rhabdomyomas. The most common finding with brain magnetic resonance imaging (MRI) was cortical tubers (85%). EEG examinations revealed diffuse and multifocal epileptic disorder in 5 (24%), focal epileptic disorder in 8 (38%), and hypsarrhythmia in 8 (38%) patients. 38% of the patients with epilepsy were diagnosed with refractory epilepsy. Severe intellectual disability and / or autism were detected in 11 (32%) patients. The number of patients with renal angiomyolipoma (p:0.001) were significantly higher in drug resistant epilepsy patients and also TSC-associated neuropsychiatric disorders (TAND) (p:0.001) rate was significantly higher in epilepsy patients.

Conclusion: The disease should be followed with a multidisciplinary approach. Although not included in the diagnostic criteria, it should be kept in mind that epilepsy, intellectual disability and neuropsychiatric disorders frequently accompany.

Anahtar Kelimeler

Tuberoussclerosis Complex Epilepsy Intellectual Disability

Kaynakça

  • 1. Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet. 2008;372(9639):657–68. PMID:18722871
  • 2. Hallett L, Foster T, Liu Z, Blieden M, Valentim J. Burden of disease and unmet needs in tuberous sclerosis complex with neurological manifestations: systematic review. Curr Med Res Opin. 2011;27(8): 1571-83. PMID:21692602
  • 3. Schwartz RA, Fernández G, Kotulska K et al. Tuberous sclerosis complex: advances in diagnosis, genetics, and management. J Am Acad Dermatol. 2007; 57(2):189-202. PMID:17637444
  • 4. Northrup H, Krueger D. International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 2013; 49(4):243–54. PMID:24053982
  • 5. Krueger DA, Northrup H. International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013; 49(4):255–265. PMID:24053983
  • 6. Curatolo P, Moavero R, de Vries PJ. Neurological and neuropsychiatric aspects of tuberous sclerosis complex. Lancet Neurol. 2015;14(7):733-45. PMID:26067126
  • 7. Holmes GL, Stafstrom CE; Tuberous Sclerosis Study Group. Tuberous sclerosis complex and epilepsy: recent developments and future challenges. Epilepsia. 2007;48(4):617-30. PMID:17386056
  • 8. Smalley SL, Burger F, Smith M. Phenotypic variation of tuberous sclerosis in a single extended kindred. J Med Genet. 1994;31(10):761-5. PMID:7837252
  • 9. Saltık S, Karatoprak EY, Taşel B. Characteristics and the clinical course of epilepsy in patients with tuberous sclerosis complex. Türk Pediatri Arş. 2013;48(2):123-30. doi:10.4274/tpa:116
  • 10. Józwiak S, Schwartz RA, Janniger CK,Michałowicz R, Chmielik J. Skin lesions in children with tuberous sclerosis complex: their prevalence, natural course, and diagnostic significance. Int J Dermatol. 1998;37(12):911-7. PMID:9888331
  • 11. Au KS, Williams AT, Roach ES, Batchelor L, Sparagana SP, Delgado MR et al. Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States. Genet Med. 2007;9(2):88-100. PMID:17304050
  • 12. Mettin RR, Merkenschlager A, Bernhard MK, Elix H, Hirsch W, Kiess W et al. Wide spectrum of clinical manifestations in children with tuberous sclerosis complex–Follow-up of 20 children. Brain Dev. 2014;36(4):306-14. PMID:23751858
  • 13. Chu-Shore CJ, Major P, Camposano S, Muzykewicz D, Thiele EA. The natural history of epilepsy in tuberous sclerosis complex. Epilepsia. 2010; 51(7):1236–41. PMID:20041940
  • 14. Joinson C, O’Callaghan FJ, Osborne JP, Martyn C, Harris T, Bolton PF. Learning disability and epilepsy in an epidemiological sample of individuals with tuberous sclerosis complex. Psychol Med. 2003;33(2):335–44. PMID:12622312
  • 15. Wang YY, Pang LY, Ma SF, Zhang MN, Liu LY, Zou LP. Epilepsy may be the major risk factor of mental retardation in children with tuberous sclerosis: A retrospective cohort study. Epilepsy Behav. 2017;77:13-8. PMID:29073472
  • 16. Jozwiak S, Kotulska K, Domanska-Pakiela D, Lojszczyk B, Syczewska M, Chmielewski D, 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 Sep 2011;15(5):424–31. PMID: Epilepsy Behav. 2017;77:13-8.
  • 17. Mizuguchi M, Takashima S. Neuropathology of tuberous sclerosis. Brain Dev. 2001; 23(7): 508-15. PMID:11701246
  • 18. Goodman M, Lamm SH, Engel A  Shepherd CW, Houser OW, Gomez MR. Cortical tuber count: a biomarker indicating neurologic severity of tuberous sclerosis complex. J Child Neurol. 1997;12(2):85-90. PMID:9075016
  • 19. Jóźwiak S, Domańska-Pakieła D, Kwiatkowski DJ, Kotulska K. Multiple cardiac rhabdomyomas as a sole symptom of tuberous sclerosis complex: case report with molecular confirmation. J Child Neurol. 2005;20(12):988-9. PMID:16417848
  • 20. Camposano SE, Greenberg E, Kwiatkowski DJ, Thiele EA. Distinct clinical characteristics of tuberous sclerosis complex patients with no mutation identified. Ann Human Genet. 2009;73(2):141-6. PMID:19133941
  • 21. Peron A, Vignoli A, La Briola F, Morenghi E, Tansini L, Alfano RM et al. Deep phenotyping of patients with Tuberous Sclerosis Complex and no mutation identified in TSC1 and TSC2. Eur J Med Genet. 2018;61(7):403-10. PMID: 29432982
  • 22. Lin S, Zeng JB, Zhao GX, Yang ZZ, Huang HP, Lin MT et al. Tuberous Sclerosis Complex in Chinese patients: Phenotypic analysis and mutational screening of TSC1/TSC2 genes. Seizure. 2019;71:322-7. PMID:31525612
  • 23. Dabora SL, Jozwiak S, Franz DN, Roberts PS, Nieto A, Chung J 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;68(1):64-80. PMID:11112665

Tüberoskleroz kompleksi tanılı hastaların değerlendirilmesi

Yıl 2020, Cilt: 4 Sayı: 1, 82 - 87, 02.03.2020

Zeynep Selen Karalök Alev Güven Hüsniye Altan Zeynep Öztürk Nesrin Ceylan Esra Gürkaş

https://doi.org/10.30565/medalanya.584167

Öz

Amaç: Tüberoskleroz kompleksi (TSK) vücutta birçok organın tutulumu ile karakterize, otozomal dominant kalıtım gösteren genetik bir rahatsızlıktır. Bu çalışmada TSK tanı kriterlerinin ve tanı kriterleri dışındaki bulguların sıklığını belirlemek amaçlanmıştır.

Hastalar ve Yöntemler: TSK tanılı 35 hastanın verileri geriye dönük olarak incelendi. Hastaların tanısı, 2012 yılında güncellenen TSK'nin tanı kriterlerine göre değerlendirildi. Tanısal olmayan kriterler olarak; epilepsi, ilaca dirençli epilepsi, elektroensefalografi (EEG) tiplerini (fokal, diffüz-multifokal ve hiperaritmi) ve TAND'ı (TSC ile ilişkili nöropsikiyatrik bozukluklar) (zihinsel yetersizlik ve / veya otizm ve öğrenme yetersizliği) inceledik.

Bulgular: Yirmi bir hasta (%60) nöbet geçirme, 9 hasta (%26) hipopigmente lekelenmeler ve 5 hasta (%14) kardiyak rabdomiyomlar nedeniyle başvurmuştu. Beyin magnetik rezonans görüntüleme (MRG) ile en sık saptanan bulgu kortikal tüberlerdi (%85). Nöbet geçiren hastaların EEG incelemelerinde 5’inde (%24) yaygın ve multifokal epileptik bozukluk, 8’inde (%38) fokal epileptik bozukluk ve 8’inde (%38) hipsaritmi paterni saptandı. Epilepsi tanısı ile izlenen olguların %38’i dirençli epilepsi tanısına sahipti. Ağır derecede entelektüel yetersizlik ve/veya otizm 11 (%32) hastada saptandı. Dirençli epilepsi grubunda böbrek anjiomiyolipomaları olan hasta sayısı anlamlı olarak fazlaydı (p:0.001) ve aynı zamanda tüberoskleroz ile ilişkili nöropsikiyatrik bozuklukların oranı anlamlı olarak epilepsi grubunda yüksekti (p:0.001).

Sonuç: Hastalığın multidisipliner bir yaklaşım ile takip edilmesi gerekmektedir. Tanı kriterlerinde yer almasa da epilepsi, entelektüel yetersizlik ve nöropsikiyatrik bozuklukların sık eşlik ettiği akılda tutulmalıdır.

Anahtar Kelimeler

Tüberoskleroz Kompleksi Epilepsi Entellektüel yetersizlik

Kaynakça

  • 1. Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet. 2008;372(9639):657–68. PMID:18722871
  • 2. Hallett L, Foster T, Liu Z, Blieden M, Valentim J. Burden of disease and unmet needs in tuberous sclerosis complex with neurological manifestations: systematic review. Curr Med Res Opin. 2011;27(8): 1571-83. PMID:21692602
  • 3. Schwartz RA, Fernández G, Kotulska K et al. Tuberous sclerosis complex: advances in diagnosis, genetics, and management. J Am Acad Dermatol. 2007; 57(2):189-202. PMID:17637444
  • 4. Northrup H, Krueger D. International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 2013; 49(4):243–54. PMID:24053982
  • 5. Krueger DA, Northrup H. International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013; 49(4):255–265. PMID:24053983
  • 6. Curatolo P, Moavero R, de Vries PJ. Neurological and neuropsychiatric aspects of tuberous sclerosis complex. Lancet Neurol. 2015;14(7):733-45. PMID:26067126
  • 7. Holmes GL, Stafstrom CE; Tuberous Sclerosis Study Group. Tuberous sclerosis complex and epilepsy: recent developments and future challenges. Epilepsia. 2007;48(4):617-30. PMID:17386056
  • 8. Smalley SL, Burger F, Smith M. Phenotypic variation of tuberous sclerosis in a single extended kindred. J Med Genet. 1994;31(10):761-5. PMID:7837252
  • 9. Saltık S, Karatoprak EY, Taşel B. Characteristics and the clinical course of epilepsy in patients with tuberous sclerosis complex. Türk Pediatri Arş. 2013;48(2):123-30. doi:10.4274/tpa:116
  • 10. Józwiak S, Schwartz RA, Janniger CK,Michałowicz R, Chmielik J. Skin lesions in children with tuberous sclerosis complex: their prevalence, natural course, and diagnostic significance. Int J Dermatol. 1998;37(12):911-7. PMID:9888331
  • 11. Au KS, Williams AT, Roach ES, Batchelor L, Sparagana SP, Delgado MR et al. Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States. Genet Med. 2007;9(2):88-100. PMID:17304050
  • 12. Mettin RR, Merkenschlager A, Bernhard MK, Elix H, Hirsch W, Kiess W et al. Wide spectrum of clinical manifestations in children with tuberous sclerosis complex–Follow-up of 20 children. Brain Dev. 2014;36(4):306-14. PMID:23751858
  • 13. Chu-Shore CJ, Major P, Camposano S, Muzykewicz D, Thiele EA. The natural history of epilepsy in tuberous sclerosis complex. Epilepsia. 2010; 51(7):1236–41. PMID:20041940
  • 14. Joinson C, O’Callaghan FJ, Osborne JP, Martyn C, Harris T, Bolton PF. Learning disability and epilepsy in an epidemiological sample of individuals with tuberous sclerosis complex. Psychol Med. 2003;33(2):335–44. PMID:12622312
  • 15. Wang YY, Pang LY, Ma SF, Zhang MN, Liu LY, Zou LP. Epilepsy may be the major risk factor of mental retardation in children with tuberous sclerosis: A retrospective cohort study. Epilepsy Behav. 2017;77:13-8. PMID:29073472
  • 16. Jozwiak S, Kotulska K, Domanska-Pakiela D, Lojszczyk B, Syczewska M, Chmielewski D, 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 Sep 2011;15(5):424–31. PMID: Epilepsy Behav. 2017;77:13-8.
  • 17. Mizuguchi M, Takashima S. Neuropathology of tuberous sclerosis. Brain Dev. 2001; 23(7): 508-15. PMID:11701246
  • 18. Goodman M, Lamm SH, Engel A  Shepherd CW, Houser OW, Gomez MR. Cortical tuber count: a biomarker indicating neurologic severity of tuberous sclerosis complex. J Child Neurol. 1997;12(2):85-90. PMID:9075016
  • 19. Jóźwiak S, Domańska-Pakieła D, Kwiatkowski DJ, Kotulska K. Multiple cardiac rhabdomyomas as a sole symptom of tuberous sclerosis complex: case report with molecular confirmation. J Child Neurol. 2005;20(12):988-9. PMID:16417848
  • 20. Camposano SE, Greenberg E, Kwiatkowski DJ, Thiele EA. Distinct clinical characteristics of tuberous sclerosis complex patients with no mutation identified. Ann Human Genet. 2009;73(2):141-6. PMID:19133941
  • 21. Peron A, Vignoli A, La Briola F, Morenghi E, Tansini L, Alfano RM et al. Deep phenotyping of patients with Tuberous Sclerosis Complex and no mutation identified in TSC1 and TSC2. Eur J Med Genet. 2018;61(7):403-10. PMID: 29432982
  • 22. Lin S, Zeng JB, Zhao GX, Yang ZZ, Huang HP, Lin MT et al. Tuberous Sclerosis Complex in Chinese patients: Phenotypic analysis and mutational screening of TSC1/TSC2 genes. Seizure. 2019;71:322-7. PMID:31525612
  • 23. Dabora SL, Jozwiak S, Franz DN, Roberts PS, Nieto A, Chung J 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;68(1):64-80. PMID:11112665
Toplam 23 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular İç Hastalıkları
Bölüm Araştırma Makalesi
Yazarlar

Zeynep Selen Karalök 0000-0001-5465-7380

Alev Güven Bu kişi benim 0000-0001-8226-0516

Hüsniye Altan 0000-0002-2096-8700

Zeynep Öztürk 0000-0003-0500-0619

Nesrin Ceylan 0000-0001-5844-1261

Esra Gürkaş 0000-0003-3942-5105

Yayımlanma Tarihi 2 Mart 2020
Gönderilme Tarihi 28 Haziran 2019
Kabul Tarihi 18 Kasım 2019
Yayımlandığı Sayı Yıl 2020 Cilt: 4 Sayı: 1

Kaynak Göster

Vancouver Karalök ZS, Güven A, Altan H, Öztürk Z, Ceylan N, Gürkaş E. Evaluation of Tuberous Sclerosis Complex Patients. Acta Med. Alanya. 2020;4(1):82-7.

9705 

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