Clinical summary and analysis of patients with refractory epilepsy in tuberous sclerosis complex with peripheral blood gene negative_Journal of Epilepsy

Authors：

HE Jing ,  ZHOU Wenjing , SHI Jie , LIN Jiuluan , WANG Haixiang , ZHANG Bingqing

Department of Epilepsy center, Tsinghua University Yuquan Hospital, Beijing 100049, China;

Corresponding author：

ZHOU Wenjing, Email: closejeo@hotmail.com

Keywords：

Tuberous sclerosis complex; Gene negative; Mosaic mutation; Refractory epilepsy

DOI：

10.7507/2096-0247.202405003

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Objective Tuberous sclerosis complex (TSC) is a multisystem disease, which often manifests as refractory epilepsy in the nervous system and multifocality in Magnetic resonance imaging (MRI). We summarized patients with TSC whose peripheral blood gene test was negative,and analyzed their medical history, EEG, MRI and postoperative conditions. Methods We summarized and analyzed 205 patients with TSC diagnosed clinically and pathologically and underwent surgery from April 2008 to February 2024. 11 patients with TSC whose peripheral blood gene test was negative and underwent surgery were screened out.All patients underwent gene examination, MRI and long-range video EEG monitoring. All patients underwent detailed preoperative evaluation and direct resection surgery, intracranial electrode thermocoagulation surgery or laser surgery. Results Of the 11 patients with peripheral blood gene test negative, 11 (100%) patients achieved Engel Ⅰ within 1 year after surgery, and 10 (91%) patients achieved Engel Ⅰwithin 2 years. The median age of onset of 11 patients was 6 months, and 8 patients (73%) had onset less than 1 year old. All patients had multiple nodules in the brain. Except for the brain, the changes of the other organs were polycystic kidney and skin changes in 2 patients, skin changes in 8 patients, and normal in 1 patients. Conclusion TSC patients with peripheral blood gene negative who have young onset age, frequent seizures, and multiple nodules on MRI often present with refractory epilepsy. However, the postoperative effect is good, and the postoperative EEG of most patients is normal.

Citation： HE Jing, ZHOU Wenjing, SHI Jie, LIN Jiuluan, WANG Haixiang, ZHANG Bingqing. Clinical summary and analysis of patients with refractory epilepsy in tuberous sclerosis complex with peripheral blood gene negative. Journal of Epilepsy, 2024, 10(4): 295-298. doi: 10.7507/2096-0247.202405003 Copy

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2.	Nicola S, Giusy CP, Luca P, et al. Current role of surgery for tuberous sclerosis complex-associated epilepsy. Pediatr Investig, 2022, 6(1): 16-22.
3.	Nicola S, Chiara P, Luca P, et al. Surgery for drug-resistant tuberous sclerosis complex-associated epilepsy: who, when, and what. Epileptic Disorders, 2021, 23(1): 53-73.
4.	Holmes GL, Stafstrom CE. Tuberous Sclerosis Study Group. Tuberous sclerosis complex and epilepsy: recent developments andfuture challenges. Epilepsia, 2007, 48(4): 617-630.
5.	van Slegtenhorst M, Nellist M, Nagelkerken B, et al. Interaction betweenhamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet, 1998, 7(6): 1053-1057.
6.	Katarzyna K, Krinio G, Joannes MG, et al. Comprehensive genetic and phenotype analysis of 95 individuals with mosaic tuberous sclerosis complex. Am J Hum Genet, 2023, 110(6): 979-988.
7.	Magdalena ET, Kira AD, Jennifer G, et al. Mosaic and intronic mutations in TSC1/TSC2 explain the majority of TSC patients with no mutation identified by conventional testing. PLoS Genet, 2015, 11(11): e1005637.
8.	Laura SF , Deborah AP, John PW, et al. Tuberous sclerosis complex genotypes and developmental phenotype. Pediatric Neurology, 2019, 96: 58-63.
9.	Ding Yf , Zhou Yf, Yu Lf, et al . Correlation between epilepsy and genotype: a large retrospective tuberous sclerosis complex cohort. Seizure, 2021, 91: 273–277.
10.	Angela P, Aglaia V, Francesca LB, 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): 403-410.
11.	Black, ME, Hedgire, SS, Camposano, S, et al. Hepatic manifestations of tuberous sclerosis complex: a genotypic and phenotypic analysis. Clinical Genetics, 2012, 82: 552-557.
12.	Dabora SL, Jozwiak S, Franz DN, 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.
13.	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: 88-100.
14.	Camposano SE, Greenberg E, Kwiatkowski DJ, et al. Distinct clinical characteristics of tuberous sclerosis complex patients with no mutation identified. Ann Hum Genet, 2009, 73(2): 141-146.
15.	Aria F, Shaun DR, Alexander GW, et al. Resective epilepsy surgery for tuberous sclerosis in children: determining predictors of seizure outcomes in a multicenter retrospective cohort study. Neurosurgery, 2015, 77(4): 517-524.

1. Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med, 2006, 355(13): 1345-1356.
2. Nicola S, Giusy CP, Luca P, et al. Current role of surgery for tuberous sclerosis complex-associated epilepsy. Pediatr Investig, 2022, 6(1): 16-22.
3. Nicola S, Chiara P, Luca P, et al. Surgery for drug-resistant tuberous sclerosis complex-associated epilepsy: who, when, and what. Epileptic Disorders, 2021, 23(1): 53-73.
4. Holmes GL, Stafstrom CE. Tuberous Sclerosis Study Group. Tuberous sclerosis complex and epilepsy: recent developments andfuture challenges. Epilepsia, 2007, 48(4): 617-630.
5. van Slegtenhorst M, Nellist M, Nagelkerken B, et al. Interaction betweenhamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet, 1998, 7(6): 1053-1057.
6. Katarzyna K, Krinio G, Joannes MG, et al. Comprehensive genetic and phenotype analysis of 95 individuals with mosaic tuberous sclerosis complex. Am J Hum Genet, 2023, 110(6): 979-988.
7. Magdalena ET, Kira AD, Jennifer G, et al. Mosaic and intronic mutations in TSC1/TSC2 explain the majority of TSC patients with no mutation identified by conventional testing. PLoS Genet, 2015, 11(11): e1005637.
8. Laura SF , Deborah AP, John PW, et al. Tuberous sclerosis complex genotypes and developmental phenotype. Pediatric Neurology, 2019, 96: 58-63.
9. Ding Yf , Zhou Yf, Yu Lf, et al . Correlation between epilepsy and genotype: a large retrospective tuberous sclerosis complex cohort. Seizure, 2021, 91: 273–277.
10. Angela P, Aglaia V, Francesca LB, 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): 403-410.
11. Black, ME, Hedgire, SS, Camposano, S, et al. Hepatic manifestations of tuberous sclerosis complex: a genotypic and phenotypic analysis. Clinical Genetics, 2012, 82: 552-557.
12. Dabora SL, Jozwiak S, Franz DN, 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.
13. 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: 88-100.
14. Camposano SE, Greenberg E, Kwiatkowski DJ, et al. Distinct clinical characteristics of tuberous sclerosis complex patients with no mutation identified. Ann Hum Genet, 2009, 73(2): 141-146.
15. Aria F, Shaun DR, Alexander GW, et al. Resective epilepsy surgery for tuberous sclerosis in children: determining predictors of seizure outcomes in a multicenter retrospective cohort study. Neurosurgery, 2015, 77(4): 517-524.

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