Mutiple factors analusis of the influence of epilepsy onset age on the patients with tuberous sclerosis complex_Journal of Epilepsy

Authors：

GUO Jing , LI Danfang , YAN Hongjun ,  LI Hua

Eipleptic Centre, Guangdong 999 Brain Hospital, Guangzhou 510510, China;

Corresponding author：

LI Hua, Email: lihua1051@163.com

Keywords：

Tuberous sclerosis; Age of onset of epilepsy; TSC gene; Clinical phenotype; Rapamycin

DOI：

10.7507/2096-0247.20200033

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Objective To investigate the relationships between the onset age, genotype, clinical phenotype and the efficacy of Rapamycin in patients with tuberous sclerosis complex.Methods Retrospectively analyze the clinical data of patients with tuberous sclerosis complex (TSC) who were diagnosed with epilepsy in Guangdong Sanjiu Brain Hospital from October 2013 to December 2018. Meanwhile, the relationships between the onset age of epilepsy and genotype, clinical phenotype and Rapamycin efficacy were analyzed comprehensively.Results TSC gene was detected in 104 patients with tuberous sclerosis complex, of which 85 (81.7%) were positive and 44 (51.8%) were males as well as 41 (48.2%) were females, with an average age of (4.0±4.9) years old. And there were 34 (40.0%) TSC1 mutations and 51 (60.0%) TSC2 mutations. The patients were divided into 3 groups according to their ages: ≤1 year old, 1 ~ 6 years old and ≥6 years old. Among them, 31 cases (36.5%) were in the ≤1 year old group, 31 cases (36.5%) in the 1 ~ 6 years old group and 23 cases (27.0%) in the ≥6 years old group. Through statistical analysis, we found that the onset age of epilepsy in patients with TSC1 and TSC2 gene mutations was statistically different (χ²=9.030, P=0.011). Further analysis of the relationship between the onset age of epilepsy and other clinical phenotypes showed that there were statistical differences in the probability of mental retardation and spasm seizure in different onset age groups of epilepsy (P<0.05). In addition, patients with epilepsy onset age ≤1 year old are more likely to have renal disease and patients with epilepsy onset age ≥6 years old are more likely to have SEGAs. There was no significant difference between the onset age of epilepsy and the efficacy of Rapamycin (P>0.05).Conclusion TSC2 mutation, mental retardation and spasm seizure are more likely to occur in patients with epilepsy onset age ≤1 year old. The study on multiple factors of epilepsy onset age may have a certain guiding role in judging the development and prognosis of TSC with epilepsy.

Citation： GUO Jing, LI Danfang, YAN Hongjun, LI Hua. Mutiple factors analusis of the influence of epilepsy onset age on the patients with tuberous sclerosis complex. Journal of Epilepsy, 2020, 6(3): 188-192. doi: 10.7507/2096-0247.20200033 Copy

1.	O’Callaghan FJ, Shiell AW, Osborne JP, et al. Prevalence of tuberous sclerosis estimated by capture-recapture analysis. Lancet, 1998, 351(9114): 1490.
2.	Hong CH, Tu HP, Lin JR, et al. An estimation of the incidence of tuberous sclerosis complex in a nationwide retrospective cohort study (1997-2010). Br J Dermatol, 2016, 174(6): 1282-1289.
3.	Roach ES. Applying the lessons of tuberous sclerosis: the 2015 Hower Award Lecture. Pediatr Neurol, 2016, 63: 6-22.
4.	Curatolo P, Moavero R, de Vries PJ. Neurological and neuropsychiatric aspects of tuberous sclerosis complex. Lancet Neurol, 2015, 14(7): 733-745.
5.	Saxena A, Sampson JR. Epilepsy in tuberous sclerosis: phenotypes, mechanisms, and treatments. Semin Neurol, 2015, 35(3): 269-276.
6.	Overwater IE, Bindels-de HK, Rietman AB, et al. Epilepsy in children with tuberous sclerosis complex: chance of remission and response to antiepileptic drugs. Epilepsia, 2015, 56(8): 1239-1245.
7.	Henske EP, Jozwiak S, Kingswood JC, et al. Tuberous sclerosis complex. Nat Rev Dis Primers, 2016, 2: 16035.
8.	Cheadle JP, Reeve MP, Sampson JR, et al. Molecular genetic advances in tuberous sclerosis. Hum Genet, 2000, 107(2): 97-114.
9.	Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet, 2008, 372(9639): 657-668.
10.	van Slegtenhorst M, de Hoogt R, Hermans C, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science, 1997, 277(5327): 805-808.
11.	Lam HC, Nijmeh J, Henske EP. New developments in the genetics and pathogenesis of tumours in tuberous sclerosis complex. J Pathol, 2017, 241(2): 219-225.
12.	Curatolo P, Maria BL. Tuberous sclerosis. Handb Clin Neurol, 2013, 111: 323-331.
13.	Jozwiak S, Schwartz RA, Janniger CK, et al. Usefulness of diagnostic criteria of tuberous sclerosis complex in pediatric patients. J Child Neurol, 2000, 15(10): 652-659.
14.	Holmes GL, Stafstrom CE. Tuberous sclerosis complex and epilepsy: recent developments and future challenges. Epilepsia, 2007, 48(4): 617-630.
15.	Thiele EA. Managing epilepsy in tuberous sclerosis complex. J Child Neurol, 2004, 19(9): 680-686.
16.	van Eeghen AM, Black ME, Pulsifer MB, et al. Genotype and cognitive phenotype of patients with tuberous sclerosis complex. Eur J Hum Genet, 2012, 20(5): 510-515.
17.	Au KS, Williams AT, Roach ES, 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.
18.	Avgeris S, Fostira F, Vagena A, et al. Mutational analysis of TSC1 and TSC2 genes in Tuberous Sclerosis Complex patients from Greece. Sci Rep, 2017, 7(1): 16697.
19.	Rosset C, Vairo F, Bandeira IC, et al. Molecular analysis of TSC1 and TSC2 genes and phenotypic correlations in Brazilian families with tuberous sclerosis. PLoS One, 2017, 12(10): e185713.
20.	Yang G, Shi ZN, Meng Y, et al. Phenotypic and genotypic characterization of Chinese children diagnosed with tuberous sclerosis complex. Clin Genet, 2017, 91(5): 764-768.
21.	Kothare SV, Singh K, Chalifoux JR, et al. Severity of manifestations in tuberous sclerosis complex in relation to genotype. Epilepsia, 2014, 55(7): 1025-1029.
22.	吴璇, 孙丹, 刘智胜, 等. 结节性硬化症患儿 TSC1/TSC2 突变基因型与表型的相关性分析. 中华实用儿科临床杂志, 2015, (30): 466.
23.	Overwater IE, Swenker R, van der Ende EL, et al. Genotype and brain pathology phenotype in children with tuberous sclerosis complex. Eur J Hum Genet, 2016, 24(12): 1688-1695.
24.	李花, 胡湘蜀, 沈鼎烈, 等. 伴有癫痫发作的结节性硬化症患者的临床特点. 中风与神经疾病杂志, 2012, (10): 58-61.
25.	Samir H, Ghaffar HA, Nasr M. Seizures and intellectual outcome: clinico-radiological study of 30 Egyptian cases of tuberous sclerosis complex. Eur J Paediatr Neurol, 2011, 15(2): 131-137.
26.	Julich K, Sahin M. Mechanism-based treatment in tuberous sclerosis complex. Pediatr Neurol, 2014, 50(4): 290-296.
27.	Carson RP, Van Nielen DL, Winzenburger PA, et al. Neuronal and glia abnormalities in Tsc1-deficient forebrain and partial rescue by rapamycin. Neurobiol Dis, 2012, 45(1): 369-380.

1. O’Callaghan FJ, Shiell AW, Osborne JP, et al. Prevalence of tuberous sclerosis estimated by capture-recapture analysis. Lancet, 1998, 351(9114): 1490.
2. Hong CH, Tu HP, Lin JR, et al. An estimation of the incidence of tuberous sclerosis complex in a nationwide retrospective cohort study (1997-2010). Br J Dermatol, 2016, 174(6): 1282-1289.
3. Roach ES. Applying the lessons of tuberous sclerosis: the 2015 Hower Award Lecture. Pediatr Neurol, 2016, 63: 6-22.
4. Curatolo P, Moavero R, de Vries PJ. Neurological and neuropsychiatric aspects of tuberous sclerosis complex. Lancet Neurol, 2015, 14(7): 733-745.
5. Saxena A, Sampson JR. Epilepsy in tuberous sclerosis: phenotypes, mechanisms, and treatments. Semin Neurol, 2015, 35(3): 269-276.
6. Overwater IE, Bindels-de HK, Rietman AB, et al. Epilepsy in children with tuberous sclerosis complex: chance of remission and response to antiepileptic drugs. Epilepsia, 2015, 56(8): 1239-1245.
7. Henske EP, Jozwiak S, Kingswood JC, et al. Tuberous sclerosis complex. Nat Rev Dis Primers, 2016, 2: 16035.
8. Cheadle JP, Reeve MP, Sampson JR, et al. Molecular genetic advances in tuberous sclerosis. Hum Genet, 2000, 107(2): 97-114.
9. Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet, 2008, 372(9639): 657-668.
10. van Slegtenhorst M, de Hoogt R, Hermans C, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science, 1997, 277(5327): 805-808.
11. Lam HC, Nijmeh J, Henske EP. New developments in the genetics and pathogenesis of tumours in tuberous sclerosis complex. J Pathol, 2017, 241(2): 219-225.
12. Curatolo P, Maria BL. Tuberous sclerosis. Handb Clin Neurol, 2013, 111: 323-331.
13. Jozwiak S, Schwartz RA, Janniger CK, et al. Usefulness of diagnostic criteria of tuberous sclerosis complex in pediatric patients. J Child Neurol, 2000, 15(10): 652-659.
14. Holmes GL, Stafstrom CE. Tuberous sclerosis complex and epilepsy: recent developments and future challenges. Epilepsia, 2007, 48(4): 617-630.
15. Thiele EA. Managing epilepsy in tuberous sclerosis complex. J Child Neurol, 2004, 19(9): 680-686.
16. van Eeghen AM, Black ME, Pulsifer MB, et al. Genotype and cognitive phenotype of patients with tuberous sclerosis complex. Eur J Hum Genet, 2012, 20(5): 510-515.
17. Au KS, Williams AT, Roach ES, 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.
18. Avgeris S, Fostira F, Vagena A, et al. Mutational analysis of TSC1 and TSC2 genes in Tuberous Sclerosis Complex patients from Greece. Sci Rep, 2017, 7(1): 16697.
19. Rosset C, Vairo F, Bandeira IC, et al. Molecular analysis of TSC1 and TSC2 genes and phenotypic correlations in Brazilian families with tuberous sclerosis. PLoS One, 2017, 12(10): e185713.
20. Yang G, Shi ZN, Meng Y, et al. Phenotypic and genotypic characterization of Chinese children diagnosed with tuberous sclerosis complex. Clin Genet, 2017, 91(5): 764-768.
21. Kothare SV, Singh K, Chalifoux JR, et al. Severity of manifestations in tuberous sclerosis complex in relation to genotype. Epilepsia, 2014, 55(7): 1025-1029.
22. 吴璇, 孙丹, 刘智胜, 等. 结节性硬化症患儿 TSC1/TSC2 突变基因型与表型的相关性分析. 中华实用儿科临床杂志, 2015, (30): 466.
23. Overwater IE, Swenker R, van der Ende EL, et al. Genotype and brain pathology phenotype in children with tuberous sclerosis complex. Eur J Hum Genet, 2016, 24(12): 1688-1695.
24. 李花, 胡湘蜀, 沈鼎烈, 等. 伴有癫痫发作的结节性硬化症患者的临床特点. 中风与神经疾病杂志, 2012, (10): 58-61.
25. Samir H, Ghaffar HA, Nasr M. Seizures and intellectual outcome: clinico-radiological study of 30 Egyptian cases of tuberous sclerosis complex. Eur J Paediatr Neurol, 2011, 15(2): 131-137.
26. Julich K, Sahin M. Mechanism-based treatment in tuberous sclerosis complex. Pediatr Neurol, 2014, 50(4): 290-296.
27. Carson RP, Van Nielen DL, Winzenburger PA, et al. Neuronal and glia abnormalities in Tsc1-deficient forebrain and partial rescue by rapamycin. Neurobiol Dis, 2012, 45(1): 369-380.

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