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中华临床医师杂志(电子版) ›› 2021, Vol. 15 ›› Issue (08) : 571 -577. doi: 10.3877/cma.j.issn.1674-0785.2021.08.003

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结构性癫痫可能致病的遗传变异与手术适应证及预后的关系探讨
周伯丞1, 孙宇1, 吴晔2, 蔡立新1,()   
  1. 1. 100034 北京,北京大学第一医院儿童癫痫中心
    2. 100034 北京,北京大学第一医院儿童癫痫中心儿科
  • 收稿日期:2021-05-23 出版日期:2021-08-15
  • 通信作者: 蔡立新

Role of possible pathogenic genetic variants in epilepsy with structural etiology: relationship with surgical decision-making and prognosis prediction

Bocheng Zhou1, Yu Sun1, Ye Wu2, Lixin Cai1,()   

  1. 1. Pediatric Epilepsy Center, Peking University First Hospital, Beijing 100034, China
    2. Pediatric Department, Peking University First Hospital, Beijing 100034, China
  • Received:2021-05-23 Published:2021-08-15
  • Corresponding author: Lixin Cai
引用本文:

周伯丞, 孙宇, 吴晔, 蔡立新. 结构性癫痫可能致病的遗传变异与手术适应证及预后的关系探讨[J]. 中华临床医师杂志(电子版), 2021, 15(08): 571-577.

Bocheng Zhou, Yu Sun, Ye Wu, Lixin Cai. Role of possible pathogenic genetic variants in epilepsy with structural etiology: relationship with surgical decision-making and prognosis prediction[J]. Chinese Journal of Clinicians(Electronic Edition), 2021, 15(08): 571-577.

手术治疗是药物难治性癫痫有效的治疗手段。对各种可能致病的遗传变异与手术疗效关系的探讨,有利于癫痫外科在术前更好地评估并筛选患者。本文重点回顾了海马硬化、局灶性皮质发育不良、结节性硬化、半侧巨脑畸形、下丘脑错构瘤以及海绵状血管瘤中胚系变异与手术疗效及手术适应证的关系,总结了癫痫相关肿瘤中的体细胞变异对手术预后的影响,并对现有的手术适应证提出建议。

Epileptic surgery is an effective treatment for drug-refractory epilepsy. The exploration of the connection between various possible disease-causing genetic variants and the surgical outcome is of benefit to presurgical evaluation. In this paper, we discuss the correlation of surgical indications and outcomes with possible pathogenic genetic variants, mainly those in hippocampal sclerosis, focal cortical dysplasia, tuberous sclerosis, hemimegalencephaly, hypothalamic hamartoma, and cavernous hemangioma. We also discuss the impact of somatic variants on surgical outcomes in epilepsy-related tumors. Based on the summarized data, we make some recommendations for the existing surgical decision-making.

1
Fiest KM, Sauro KM, Wiebe S, et al. Prevalence and incidence of epilepsy: A systematic review and meta-analysis of international studies [J]. Neurology, 2017, 88(3): 296-303.
2
Kalilani L, Sun X, Pelgrims B, et al. The epidemiology of drug-resistant epilepsy: A systematic review and meta-analysis [J]. Epilepsia, 2018, 59(12): 2179-2193.
3
West S, Nevitt SJ, Cotton J, et al. Surgery for epilepsy [J]. Cochrane Database Syst Rev, 2019, 6(6): Cd010541.
4
Ryvlin P, Cross JH, Rheims S. Epilepsy surgery in children and adults [J]. Lancet Neurol, 2014, 13(11): 1114-1126.
5
蔡立新, 陈佳, 陈倩, 等. 癫痫外科治疗术前评估规范(草案) [J]. 癫痫杂志, 2020, 6(4): 273-295.
6
Scerri T, Riseley JR, Gillies G, et al. Familial cortical dysplasia type ⅡA caused by a germline mutation in DEPDC5 [J]. Ann Clin Transl Neurol, 2015, 2(5): 575-580.
7
Kasperaviciute D, Catarino CB, Matarin M, et al. Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A [J]. Brain, 2013, 136(Pt 10): 3140-3150.
8
Blumcke I, Spreafico R, Haaker G, et al. Histopathological findings in brain tissue obtained during epilepsy surgery [J]. N Engl J Med, 2017, 377(17): 1648-1656.
9
Lee JH, Huynh M, Silhavy JL, et al. De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly [J]. Nat Genet, 2012, 44(8): 941-945.
10
Poduri A, Evrony GD, Cai X, et al. Somatic activation of AKT3 causes hemispheric developmental brain malformations [J]. Neuron, 2012, 74(1): 41-48.
11
Jansen LA, Mirzaa GM, Ishak GE, et al. PI3K/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia [J]. Brain, 2015, 138(Pt 6): 1613-1628.
12
Leventer RJ, Scerri T, Marsh AP, et al. Hemispheric cortical dysplasia secondary to a mosaic somatic mutation in MTOR [J]. Neurology, 2015, 84(20): 2029-2032.
13
Nakashima M, Saitsu H, Takei N, et al. Somatic Mutations in the MTOR gene cause focal cortical dysplasia type Ⅱb [J]. Ann Neurol, 2015, 78(3): 375-386.
14
Griffin NG, Cronin KD, Walley NM, et al. Somatic uniparental disomy of Chromosome 16p in hemimegalencephaly [J]. Cold Spring Harb Mol Case Stud, 2017, 3(5): a001735..
15
Baldassari S, Ribierre T, Marsan E, et al. Dissecting the genetic basis of focal cortical dysplasia: a large cohort study [J]. Acta Neuropathol, 2019, 138(6): 885-900.
16
Pelorosso C, Watrin F, Conti V, et al. Somatic double-hit in MTOR and RPS6 in hemimegalencephaly with intractable epilepsy [J]. Hum Mol Genet, 2019, 28(22): 3755-3765.
17
Salinas V, Vega P, Piccirilli MV, et al. Identification of a somatic mutation in the RHEB gene through high depth and ultra-high depth next generation sequencing in a patient with Hemimegalencephaly and drug resistant Epilepsy [J]. Eur J Med Genet, 2019, 62(11): 103571.
18
Lee WS, Stephenson SEM, Pope K, et al. Genetic characterization identifies bottom-of-sulcus dysplasia as an mTORopathy [J]. Neurology, 2020, 95(18): e2542-e2551.
19
Thom M. Review: Hippocampal sclerosis in epilepsy: a neuropathology review [J]. Neuropathol Appl Neurobiol, 2014, 40(5): 520-543.
20
Shinnar S. Febrile Seizures and Mesial Temporal Sclerosis [J]. Epilepsy Curr, 2003, 3(4): 115-118.
21
Walker MC. Hippocampal Sclerosis: Causes and Prevention [J]. Semin Neurol, 2015, 35(3): 193-200.
22
Vezyroglou A, Varadkar S, Bast T, et al. Focal epilepsy in SCN1A-mutation carrying patients: is there a role for epilepsy surgery? [J]. Dev Med Child Neurol, 2020, 62(11): 1331-1335.
23
Skjei KL, Church EW, Harding BN, et al. Clinical and histopathological outcomes in patients with SCN1A mutations undergoing surgery for epilepsy [J]. J Neurosurg Pediatr, 2015, 16(6): 668-674.
24
Scheffer IE, Harkin LA, Grinton BE, et al. Temporal lobe epilepsy and GEFS+ phenotypes associated with SCN1B mutations [J]. Brain, 2007, 130(Pt 1): 100-109.
25
Xiong W, Tang L, Lu L, et al. Gap Activity TOward Rags 1 variants in Chinese people with sporadic drug-resistant focal epilepsy [J]. Acta Neurol Scand, 2019, 139(3): 247-253.
26
Wouters H, Fonteyne A, Lagae L, et al. Specific memory impairment in a multiple disabled male with fragile X syndrome and temporal lobe epilepsy [J]. Dev Med Child Neurol, 2006, 48(5): 378-382.
27
Kenmuir C, Richardson M, Ghearing G. Surgical treatment for medically refractory focal epilepsy in a patient with fragile X syndrome [J]. Brain Dev, 2015, 37(9): 916-918.
28
Liu JY, Kasperavičiūtė D, Martinian L, et al. Neuropathology of 16p13.11 deletion in epilepsy [J]. PLoS One, 2012, 7(4): e34813.
29
Catarino CB, Kasperavičiūtė D, Thom M, et al. Genomic microdeletions associated with epilepsy: not a contraindication to resective surgery [J]. Epilepsia, 2011, 52(8): 1388-1392.
30
Johnson J, Mercado-Ayon E, Mercado-Ayon Y, et al. Mitochondrial dysfunction in the development and progression of neurodegenerative diseases [J]. Arch Biochem Biophys, 2021, 702: 108698.
31
Lu B, Guo S. Mechanisms linking mitochondrial dysfunction and proteostasis failure [J]. Trends Cell Biol, 2020, 30(4): 317-328.
32
Azakli H, Gurses C, Arikan M, et al. Whole mitochondrial DNA variations in hippocampal surgical specimens and blood samples with high-throughput sequencing: a case of mesial temporal lobe epilepsy with hippocampal sclerosis [J]. Gene, 2013, 529(1): 190-194.
33
Niehusmann P, Surges R, Von Wrede RD, et al. Mitochondrial dysfunction due to Leber's hereditary optic neuropathy as a cause of visual loss during assessment for epilepsy surgery [J]. Epilepsy Behav, 2011, 20(1): 38-43.
34
Blumcke I, Thom M, Aronica E, et al. The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission [J]. Epilepsia, 2011, 52(1): 158-174.
35
Bar-Peled L, Chantranupong L, Cherniack AD, et al. A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1 [J]. Science, 2013, 340(6136): 1100-1106.
36
Baulac S, Ishida S, Marsan E, et al. Familial focal epilepsy with focal cortical dysplasia due to DEPDC5 mutations [J]. Ann Neurol, 2015, 77(4): 675-683.
37
Carvill GL, Crompton DE, Regan BM, et al. Epileptic spasms are a feature of DEPDC5 mTORopathy [J]. Neurol Genet, 2015, 1(2): e17.
38
Baldassari S, Picard F, Verbeek NE, et al. The landscape of epilepsy-related GATOR1 variants [J]. Genet Med, 2019, 21(2): 398-408.
39
Lee WS, Stephenson SEM, Howell KB, et al. Second-hit DEPDC5 mutation is limited to dysmorphic neurons in cortical dysplasia type ⅡA [J]. Ann Clin Transl Neurol, 2019, 6(7): 1338-1344.
40
Ying Z, Wang I, Blumcke I, et al. A comprehensive clinico-pathological and genetic evaluation of bottom-of-sulcus focal cortical dysplasia in patients with difficult-to-localize focal epilepsy [J]. Epileptic Disord, 2019, 21(1): 65-77.
41
Sim JC, Scerri T, Fanjul-Fernández M, et al. Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3 [J]. Ann Neurol, 2016, 79(1): 132-137.
42
Weckhuysen S, Marsan E, Lambrecq V, et al. Involvement of GATOR complex genes in familial focal epilepsies and focal cortical dysplasia [J]. Epilepsia, 2016, 57(6): 994-1003.
43
Liu S, Yu T, Guan Y, et al. Resective epilepsy surgery in tuberous sclerosis complex: a nationwide multicentre retrospective study from China [J]. Brain, 2020, 143(2): 570-581.
44
Barba C, Parrini E, Coras R, et al. Co-occurring malformations of cortical development and SCN1A gene mutations [J]. Epilepsia, 2014, 55(7): 1009-1019.
45
Strauss KA, Puffenberger EG, Huentelman MJ, et al. Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2 [J]. N Engl J Med, 2006, 354(13): 1370-1377.
46
Rubboli G, Plazzi G, Picard F, et al. Mild malformations of cortical development in sleep-related hypermotor epilepsy due to KCNT1 mutations [J]. Ann Clin Transl Neurol, 2019, 6(2): 386-391.
47
Kurian M, Korff CM, Ranza E, et al. Focal cortical malformations in children with early infantile epilepsy and PCDH19 mutations: case report [J]. Dev Med Child Neurol, 2018, 60(1): 100-105.
48
Weckhuysen S, Holmgren P, Hendrickx R, et al. Reduction of seizure frequency after epilepsy surgery in a patient with STXBP1 encephalopathy and clinical description of six novel mutation carriers [J]. Epilepsia, 2013, 54(5): e74-80.
49
Rosenow F, Alonso-Vanegas MA, Baumgartner C, et al. Cavernoma-related epilepsy: review and recommendations for management--report of the Surgical Task Force of the ILAE Commission on Therapeutic Strategies [J]. Epilepsia, 2013, 54(12): 2025-2035.
50
Baumann CR, Acciarri N, Bertalanffy H, et al. Seizure outcome after resection of supratentorial cavernous malformations: a study of 168 patients [J]. Epilepsia, 2007, 48(3): 559-563.
51
Graeni C, Stepper F, Sturzenegger M, et al. Inherited cavernous malformations of the central nervous system: clinical and genetic features in 19 Swiss families [J]. Neurosurg Rev, 2010, 33(1): 47-51.
52
Gault J, Shenkar R, Recksiek P, et al. Biallelic somatic and germ line CCM1 truncating mutations in a cerebral cavernous malformation lesion [J]. Stroke, 2005, 36(4): 872-874.
53
Nannucci S, Pescini F, Poggesi A, et al. Familial cerebral cavernous malformation: report of a further Italian family [J]. Neurol Sci, 2009, 30(2): 143-147.
54
Wang X, Liu XW, Lee N, et al. Features of a Chinese family with cerebral cavernous malformation induced by a novel CCM1 gene mutation [J]. Chin Med J (Engl), 2013, 126(18): 3427-3432.
55
Fontes-Dantas FL, Da Fontoura Galvão G, Veloso Da Silva E, et al. Novel CCM1 (KRIT1) mutation detection in brazilian familial cerebral cavernous malformation: different genetic variants in inflammation, oxidative stress, and drug metabolism genes affect disease aggressiveness [J]. World Neurosurg, 2020, 138: 535-540. e8.
56
Da Fontoura Galvão G, Veloso Da Silva E, Fontes-Dantas FL, et al. First report of concomitant pathogenic mutations within MGC4607/CCM2 and KRIT1/CCM1 in a familial cerebral cavernous malformation patient [J]. World Neurosurg, 2020, 142: 481-486.e1.
57
D'angelo R, Scimone C, Calabrò M, et al. Identification of a novel CCM2 gene mutation in an Italian family with multiple cerebral cavernous malformations and epilepsy: a causative mutation? [J]. Gene, 2013, 519(1): 202-207.
58
Ishii K, Tozaka N, Tsutsumi S, et al. Familial cerebral cavernous malformation presenting with epilepsy caused by mutation in the CCM2 gene: A case report [J]. Medicine (Baltimore), 2020, 99(29): e19800.
59
Cigoli MS, Avemaria F, De Benedetti S, et al. PDCD10 gene mutations in multiple cerebral cavernous malformations [J]. PLoS One, 2014, 9(10): e110438.
60
Kerrigan JF, Parsons A, Tsang C, et al. Hypothalamic hamartoma: Neuropathology and epileptogenesis [J]. Epilepsia, 2017, 58 Suppl 2: 22-31.
61
Fujita A, Higashijima T, Shirozu H, et al. Pathogenic variants of DYNC2H1, KIAA0556, and PTPN11 associated with hypothalamic hamartoma [J]. Neurology, 2019, 93(3): e237-e251.
62
Craig DW, Itty A, Panganiban C, et al. Identification of somatic chromosomal abnormalities in hypothalamic hamartoma tissue at the GLI3 locus [J]. Am J Hum Genet, 2008, 82(2): 366-374.
63
Wallace RH, Freeman JL, Shouri MR, et al. Somatic mutations in GLI3 can cause hypothalamic hamartoma and gelastic seizures [J]. Neurology, 2008, 70(8): 653-655.
64
Hildebrand MS, Griffin NG, Damiano JA, et al. Mutations of the sonic hedgehog pathway underlie hypothalamic hamartoma with gelastic epilepsy [J]. Am J Hum Genet, 2016, 99(2): 423-429.
65
Rubino S, Qian J, Pinheiro-Neto CD, et al. A familial syndrome of hypothalamic hamartomas, polydactyly, and SMO mutations: a clinical report of 2 cases [J]. J Neurosurg Pediatr, 2018, 23(1): 98-103.
66
Li CD, Luo SQ, Tang J, et al. Classification of hypothalamic hamartoma and prognostic factors for surgical outcome [J]. Acta Neurol Scand, 2014, 130(1): 18-26.
67
Boerwinkle VL, Foldes ST, Torrisi SJ, et al. Subcentimeter epilepsy surgery targets by resting state functional magnetic resonance imaging can improve outcomes in hypothalamic hamartoma [J]. Epilepsia, 2018, 59(12): 2284-2295.
68
Ferrand-Sorbets S, Fohlen M, Delalande O, et al. Seizure outcome and prognostic factors for surgical management of hypothalamic hamartomas in children [J]. Seizure, 2020, 75: 28-33.
69
Qi XL, Yao K, Duan ZJ, et al. [BRAF V600E mutation and clinicopathologic characteristics in 250 cases of brain tumors associated with epilepsy] [J]. Zhonghua Bing Li Xue Za Zhi, 2018, 47(9): 664-670.
70
Slegers RJ, Blumcke I. Low-grade developmental and epilepsy associated brain tumors: a critical update 2020 [J]. Acta Neuropathol Commun, 2020, 8(1): 27.
71
Ko A, Kim SH, Kim SH, et al. Epilepsy surgery for children with low-grade epilepsy-associated tumors: factors associated with seizure recurrence and cognitive function [J]. Pediatr Neurol, 2019, 91: 50-56.
72
Qaddoumi I, Orisme W, Wen J, et al. Genetic alterations in uncommon low-grade neuroepithelial tumors: BRAF, FGFR1, and MYB mutations occur at high frequency and align with morphology [J]. Acta Neuropathol, 2016, 131(6): 833-845.
73
Gilboa T, Segel R, Zeligson S, et al. Ganglioglioma, Epilepsy, and Intellectual Impairment due to Familial TSC1 Deletion [J]. J Child Neurol, 2018, 33(7): 482-486.
74
Pekmezci M, Villanueva-Meyer JE, Goode B, et al. The genetic landscape of ganglioglioma [J]. Acta Neuropathol Commun, 2018, 6(1): 47.
75
Rivera B, Gayden T, Carrot-Zhang J, et al. Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors [J]. Acta Neuropathol, 2016, 131(6): 847-863.
76
Stone TJ, Keeley A, Virasami A, et al. Comprehensive molecular characterisation of epilepsy-associated glioneuronal tumours [J]. Acta Neuropathol, 2018, 135(1): 115-129.
77
Martinoni M, Marucci G, De Biase D, et al. BRAF V600E mutation in neocortical posterior temporal epileptogenic gangliogliomas [J]. J Clin Neurosci, 2015, 22(8): 1250-1253.
78
Kakkar A, Majumdar A, Pathak P, et al. BRAF gene alterations and enhanced mammalian target of rapamycin signaling in gangliogliomas [J]. Neurol India, 2017, 65(5): 1076-1082.
79
Zhang YX, Shen CH, Guo Y, et al. BRAF V600E mutation in epilepsy-associated glioneuronal tumors: Prevalence and correlation with clinical features in a Chinese population [J]. Seizure, 2017, 45: 102-106.
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