Değişken Odaklı Familyal Fokal Epilepsi (Çocukluktan Erişkin Döneme Kadar)
Özet
Değişken odaklara sahip ailesel fokal epilepsi (FFEVF), fokal epilepsili birden fazla aile üyesi ile karakterize, nöbet odağının aile üyeleri arasında farklılık gösterebilen ancak aynı bireyde sabit kaldığı ailesel epilepsi sendromudur. Değişken odaklı ailesel fokal epilepsi genetik nedenli epilepsi sendromları arasında yer almaktadır. Genetik tanılaması ilk olarak 1999 yılında 22. Kromozomda haritalanmıştır ve sorumlu gen olan DEPDC5, 2013 yılında ekzom dizileme yoluyla tanımlanmıştır. Bu epilepsi sendromu yaklaşık %70 penetrans ile otozomal dominant kalıtım paterni gösterir. Değişken odaklara sahip bu sendrom, Uluslararası Epilepsiye Karşı Savaş Derneği tarafından da epileptik sendromların sınıflandırılması tanı şemasına dahil edilmiştir.
Nöbetin başlama zamanı bebeklikten erişkin döneme kadar başlayabilir ve şiddeti aile üyeleri arasında önemli ölçüde değişebilir ve bazıları komorbid nöro-psikiyatrik belirtiler sergileyebilirler. Epileptik nöbetler gündüz, gece veya her ikisinde birden görülebilir ve sıklıkla frontal veya temporal loblardan kaynaklanır, ancak bazen oksipital veya paryetal loblardan da kaynaklanabilir. Değişken odaklı ailesel fokal epilepsi sendromu ancak aile öyküsü olan hastalarda tanımlanabilir. Hastanın akrabalarında en az 2 farklı fokal epilepsi sendromunun varlığı ve birden fazla kuşakta benzer klinikte hasta tanımlanması FFEVF’yi düşündürebilir. Bununla birlikte, tanı ve kalıtım paterninin doğrulanamadığı birçok aile, değişken odaklı ailesel fokal epilepsiyle ilişkili ortak varyantları taşımaktadır.
Referanslar
Dibbens LM, de Vries B, Donatello S, et al. Mutations in DEPDC5 cause familial focal epilepsy with variable foci. Nat Genet. 2013;45(5):546-551. doi:10.1038/ng.2599
Xiong L, Labuda M, Li DS, et al. Mapping of a gene determining familial partial epilepsy with variable foci to chromosome 22q11-q12. Am J Hum Genet. 1999;65(6):1698-1710. doi:10.1086/302649
Ishida S, Picard F, Rudolf G, et al. Mutations of DEPDC5 cause autosomal dominant focal epilepsies. Nat Genet. 2013;45(5):552-555. doi:10.1038/ng.2601
Specchio N, Wirrell EC, Scheffer IE, et al. International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: Position paper by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022;63(6):1398-1442. doi:10.1111/epi.17241
Morales-Corraliza J, Gómez-Garre P, Sanz R, Díaz-Otero F, Gutiérrez-Delicado E, Serratosa JM. Familial partial epilepsy with variable foci: a new family with suggestion of linkage to chromosome 22q12. Epilepsia. 2010;51(9):1910-1914. doi:10.1111/j.1528-1167.2010.02680.x
Riney K, Bogacz A, Somerville E, et al. International League Against Epilepsy classification and definition of epilepsy syndromes with onset at a variable age: position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022;63(6):1443-1474. doi:10.1111/epi.17240
Scheffer IE, Phillips HA, O'Brien CE, et al. Familial partial epilepsy with variable foci: a new partial epilepsy syndrome with suggestion of linkage to chromosome 2. Ann Neurol. 1998;44(6):890-899. doi:10.1002/ana.410440607
Berkovic SF, Serratosa JM, Phillips HA, et al. Familial partial epilepsy with variable foci: clinical features and linkage to chromosome 22q12. Epilepsia. 2004;45(9):1054-1060. doi:10.1111/j.0013-9580.2004.30502.x
Xiong L.( 2002). Identification, clinical characterization, and molecular genetic studies of familial partial epilepsy with variable foci. PhD thesis. McGill University
Scheffer IE, Heron SE, Regan BM, et al. Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations. Ann Neurol. 2014;75(5):782-787. doi:10.1002/ana.24126
Klein KM, O'Brien TJ, Praveen K, et al. Familial focal epilepsy with variable foci mapped to chromosome 22q12: expansion of the phenotypic spectrum. Epilepsia. 2012;53(8):e151-e155. doi:10.1111/j.1528-1167.2012.03585.x
Callenbach PM, van den Maagdenberg AM, Hottenga JJ, et al. Familial partial epilepsy with variable foci in a Dutch family: clinical characteristics and confirmation of linkage to chromosome 22q. Epilepsia. 2003;44(10):1298-1305. doi:10.1046/j.1528-1157.2003.62302.x
Baulac S, Ishida S, Marsan E, et al. Familial focal epilepsy with focal cortical dysplasia due to DEPDC5 mutations. Ann Neurol. 2015;77(4):675-683. doi:10.1002/ana.24368
Weckhuysen S, Marsan E, Lambrecq V, et al. Involvement of GATOR complex genes in familial focal epilepsies and focal cortical dysplasia. Epilepsia. 2016;57(6):994-1003. doi:10.1111/epi.13391
Nascimento FA, Borlot F, Cossette P, Minassian BA, Andrade DM. Two definite cases of sudden unexpected death in epilepsy in a family with a DEPDC5 mutation. Neurol Genet. 2015;1(4):e28. Published 2015 Oct 15. doi:10.1212/NXG.0000000000000028
Bagnall RD, Crompton DE, Petrovski S, et al. Exome-based analysis of cardiac arrhythmia, respiratory control, and epilepsy genes in sudden unexpected death in epilepsy. Ann Neurol. 2016;79(4):522-534. doi:10.1002/ana.24596
Baulac S. mTOR signaling pathway genes in focal epilepsies. Prog Brain Res. 2016;226:61-79. doi:10.1016/bs.pbr.2016.04.013
Marsan E, Ishida S, Schramm A, et al. Depdc5 knockout rat: A novel model of mTORopathy. Neurobiol Dis. 2016;89:180-189. doi:10.1016/j.nbd.2016.02.010
Ribierre T, Deleuze C, Bacq A, et al. Second-hit mosaic mutation in mTORC1 repressor DEPDC5 causes focal cortical dysplasia-associated epilepsy. J Clin Invest. 2018;128(6):2452-2458. doi:10.1172/JCI99384
Scerri T, Riseley JR, Gillies G, et al. Familial cortical dysplasia type IIA caused by a germline mutation in DEPDC5. Ann Clin Transl Neurol. 2015;2(5):575-580. doi:10.1002/acn3.191
Cen Z, Guo Y, Lou Y, Jiang B, Wang J, Feng J. De novo mutation in DEPDC5 associated with unilateral pachygyria and intractable epilepsy. Seizure. 2017;50:1-3. doi:10.1016/j.seizure.2017.03.014
Baldassari S, Licchetta L, Tinuper P, Bisulli F, Pippucci T. GATOR1 complex: the common genetic actor in focal epilepsies. J Med Genet. 2016;53(8):503-510. doi:10.1136/jmedgenet-2016-103883
Korenke GC, Eggert M, Thiele H, Nürnberg P, Sander T, Steinlein OK. Nocturnal frontal lobe epilepsy caused by a mutation in the GATOR1 complex gene NPRL3. Epilepsia. 2016;57(3):e60-e63. doi:10.1111/epi.13307
Wolking S, Moreau C, McCormack M, et al. Assessing the role of rare genetic variants in drug-resistant, non-lesional focal epilepsy. Ann Clin Transl Neurol. 2021;8(7):1376-1387. doi:10.1002/acn3.51374
Baldassari S, Picard F, Verbeek NE, et al. The landscape of epilepsy-related GATOR1 variants [published correction appears in Genet Med. 2018 Aug 29;:] [published correction appears in Genet Med. 2018 Sep 27;:]. Genet Med. 2019;21(2):398-408. doi:10.1038/s41436-018-0060-2
Sim JC, Scerri T, Fanjul-Fernández M, et al. Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3. Ann Neurol. 2016;79(1):132-137. doi:10.1002/ana.24502
Bacq A, Roussel D, Bonduelle T, et al. Cardiac Investigations in Sudden Unexpected Death in DEPDC5-Related Epilepsy. Ann Neurol. 2022;91(1):101-116. doi:10.1002/ana.26256
Referanslar
Dibbens LM, de Vries B, Donatello S, et al. Mutations in DEPDC5 cause familial focal epilepsy with variable foci. Nat Genet. 2013;45(5):546-551. doi:10.1038/ng.2599
Xiong L, Labuda M, Li DS, et al. Mapping of a gene determining familial partial epilepsy with variable foci to chromosome 22q11-q12. Am J Hum Genet. 1999;65(6):1698-1710. doi:10.1086/302649
Ishida S, Picard F, Rudolf G, et al. Mutations of DEPDC5 cause autosomal dominant focal epilepsies. Nat Genet. 2013;45(5):552-555. doi:10.1038/ng.2601
Specchio N, Wirrell EC, Scheffer IE, et al. International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: Position paper by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022;63(6):1398-1442. doi:10.1111/epi.17241
Morales-Corraliza J, Gómez-Garre P, Sanz R, Díaz-Otero F, Gutiérrez-Delicado E, Serratosa JM. Familial partial epilepsy with variable foci: a new family with suggestion of linkage to chromosome 22q12. Epilepsia. 2010;51(9):1910-1914. doi:10.1111/j.1528-1167.2010.02680.x
Riney K, Bogacz A, Somerville E, et al. International League Against Epilepsy classification and definition of epilepsy syndromes with onset at a variable age: position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022;63(6):1443-1474. doi:10.1111/epi.17240
Scheffer IE, Phillips HA, O'Brien CE, et al. Familial partial epilepsy with variable foci: a new partial epilepsy syndrome with suggestion of linkage to chromosome 2. Ann Neurol. 1998;44(6):890-899. doi:10.1002/ana.410440607
Berkovic SF, Serratosa JM, Phillips HA, et al. Familial partial epilepsy with variable foci: clinical features and linkage to chromosome 22q12. Epilepsia. 2004;45(9):1054-1060. doi:10.1111/j.0013-9580.2004.30502.x
Xiong L.( 2002). Identification, clinical characterization, and molecular genetic studies of familial partial epilepsy with variable foci. PhD thesis. McGill University
Scheffer IE, Heron SE, Regan BM, et al. Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations. Ann Neurol. 2014;75(5):782-787. doi:10.1002/ana.24126
Klein KM, O'Brien TJ, Praveen K, et al. Familial focal epilepsy with variable foci mapped to chromosome 22q12: expansion of the phenotypic spectrum. Epilepsia. 2012;53(8):e151-e155. doi:10.1111/j.1528-1167.2012.03585.x
Callenbach PM, van den Maagdenberg AM, Hottenga JJ, et al. Familial partial epilepsy with variable foci in a Dutch family: clinical characteristics and confirmation of linkage to chromosome 22q. Epilepsia. 2003;44(10):1298-1305. doi:10.1046/j.1528-1157.2003.62302.x
Baulac S, Ishida S, Marsan E, et al. Familial focal epilepsy with focal cortical dysplasia due to DEPDC5 mutations. Ann Neurol. 2015;77(4):675-683. doi:10.1002/ana.24368
Weckhuysen S, Marsan E, Lambrecq V, et al. Involvement of GATOR complex genes in familial focal epilepsies and focal cortical dysplasia. Epilepsia. 2016;57(6):994-1003. doi:10.1111/epi.13391
Nascimento FA, Borlot F, Cossette P, Minassian BA, Andrade DM. Two definite cases of sudden unexpected death in epilepsy in a family with a DEPDC5 mutation. Neurol Genet. 2015;1(4):e28. Published 2015 Oct 15. doi:10.1212/NXG.0000000000000028
Bagnall RD, Crompton DE, Petrovski S, et al. Exome-based analysis of cardiac arrhythmia, respiratory control, and epilepsy genes in sudden unexpected death in epilepsy. Ann Neurol. 2016;79(4):522-534. doi:10.1002/ana.24596
Baulac S. mTOR signaling pathway genes in focal epilepsies. Prog Brain Res. 2016;226:61-79. doi:10.1016/bs.pbr.2016.04.013
Marsan E, Ishida S, Schramm A, et al. Depdc5 knockout rat: A novel model of mTORopathy. Neurobiol Dis. 2016;89:180-189. doi:10.1016/j.nbd.2016.02.010
Ribierre T, Deleuze C, Bacq A, et al. Second-hit mosaic mutation in mTORC1 repressor DEPDC5 causes focal cortical dysplasia-associated epilepsy. J Clin Invest. 2018;128(6):2452-2458. doi:10.1172/JCI99384
Scerri T, Riseley JR, Gillies G, et al. Familial cortical dysplasia type IIA caused by a germline mutation in DEPDC5. Ann Clin Transl Neurol. 2015;2(5):575-580. doi:10.1002/acn3.191
Cen Z, Guo Y, Lou Y, Jiang B, Wang J, Feng J. De novo mutation in DEPDC5 associated with unilateral pachygyria and intractable epilepsy. Seizure. 2017;50:1-3. doi:10.1016/j.seizure.2017.03.014
Baldassari S, Licchetta L, Tinuper P, Bisulli F, Pippucci T. GATOR1 complex: the common genetic actor in focal epilepsies. J Med Genet. 2016;53(8):503-510. doi:10.1136/jmedgenet-2016-103883
Korenke GC, Eggert M, Thiele H, Nürnberg P, Sander T, Steinlein OK. Nocturnal frontal lobe epilepsy caused by a mutation in the GATOR1 complex gene NPRL3. Epilepsia. 2016;57(3):e60-e63. doi:10.1111/epi.13307
Wolking S, Moreau C, McCormack M, et al. Assessing the role of rare genetic variants in drug-resistant, non-lesional focal epilepsy. Ann Clin Transl Neurol. 2021;8(7):1376-1387. doi:10.1002/acn3.51374
Baldassari S, Picard F, Verbeek NE, et al. The landscape of epilepsy-related GATOR1 variants [published correction appears in Genet Med. 2018 Aug 29;:] [published correction appears in Genet Med. 2018 Sep 27;:]. Genet Med. 2019;21(2):398-408. doi:10.1038/s41436-018-0060-2
Sim JC, Scerri T, Fanjul-Fernández M, et al. Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3. Ann Neurol. 2016;79(1):132-137. doi:10.1002/ana.24502
Bacq A, Roussel D, Bonduelle T, et al. Cardiac Investigations in Sudden Unexpected Death in DEPDC5-Related Epilepsy. Ann Neurol. 2022;91(1):101-116. doi:10.1002/ana.26256
