Zusammenfassung
Die genetische Diagnostik hat in der Abklärung von Epilepsieerkrankungen stark an Bedeutung gewonnen. So ist es mittlerweile möglich, bei einem signifikanten Anteil der Patienten innerhalb überschaubarer Zeit und zu vertretbaren Kosten die genetische Ursache einer Erkrankung zu identifizieren. Sie bringt somit in zahlreichen Fällen diagnostische Gewissheit und beeinflusst die Behandlung. Die Kenntnis der genetischen Diagnose erlaubt Rückschlüsse auf das tatsächliche phänotypische Spektrum, den Verlauf, die Vererbung und gelegentlich sogar auf die Wahl der Therapie.
Abstract
Genetic testing has increasingly gained importance for diagnosing epilepsy disorders. Currently, the underlying genetic cause can be identified in a significant proportion of patients within an appropriate time and at reasonable costs. In numerous cases, it thus provides diagnostic certainty and influences treatment. Knowing the genetic cause of a disorder allows for conclusions on the true phenotypic spectrum, the course and inheritance, and occasionally it influences the choice of therapy.
Literatur
Rauch A, Hoyer J, Guth S et al (2006) Diagnostic yield of various genetic approaches in patients with unexplained developmental delay or mental retardation. Am J Med Genet A 140:2063–2074
Miller DT, Adam MP, Aradhya S et al (2010) Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 86:749–764
Kariminejad R, Lind-Thomsen A, Tümer Z et al (2011) High frequency of rare copy number variants affecting functionally related genes in patients with structural brain malformations. Hum Mutat 2011(32):1427–1435
Striano P, Coppola A, Paravidino R et al (2012) Clinical significance of rare copy number variations in epilepsy: a case-control survey using microarray-based comparative genomic hybridization. Arch Neurol 69:322–330
Mefford HC, Muhle H, Ostertag P et al (2010) Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies. PLOS Genet 6:e1000962
Mefford HC, Yendle SC, Hsu C et al (2011) Rare copy number variants are an important cause of epileptic encephalopathies. Ann Neurol 70:974–985
de Kovel CG, Trucks H, Helbig I et al (2010) Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies. Brain 133:23–32
Garofalo S, Cornacchione M, Di Costanzo A (2012) From genetics to genomics of epilepsy. Neurol Res Int 2012:876234
Lemke JR, Riesch E, Scheurenbrand T et al (2012) Targeted next generation sequencing as a diagnostic tool in epileptic disorders. Epilepsia 53:1387–1398
Dorschner MO, Amendola LM, Turner EH et al (2013) Actionable, pathogenic incidental findings in 1,000 participants’ exomes. Am J Hum Genet 93:631–640
Shahmirzadi L, Chao EC, Palmaer E, Parra MC, Tang S, Gonzalez KD (2014) Patient decisions for disclosure of secondary findings among the first 200 individuals undergoing clinical diagnostic exome sequencing. Genet Med 16:395–399
Gilissen C, Hehir-Kwa JY, Thung DT et al (2014) Genome sequencing identifies major causes of severe intellectual disability. Nature 511:344–347
Della Mina E, Ciccone R, Brustia F et al (2015) Improving molecular diagnosis in epilepsy by a dedicated high-throughput sequencing platform. Eur J Hum Genet 23:354–362
Carvill GL, Heavin SB, Yendle SC et al (2013) Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Nat Genet 45:825–830
Kodera H, Kato M, Nord AS et al (2013) Targeted capture and sequencing for detection of mutations causing early onset epileptic encephalopathy. Epilepsia 54:1262–1269
Epi4K Consortium, Epilepsy Phenome/Genome Project (2013) De novo mutations in epileptic encephalopathies. Nature 501:217–221
Veeramah KR, Johnstone L, Karafet TM et al (2013) Exome sequencing reveals new causal mutations in children with epileptic encephalopathies. Epilepsia 54:1270–1281
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Interessenkonflikt
H. O. Heyne und J. R. Lemke geben an, dass kein Interessenkonflikt besteht.
Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.
Rights and permissions
About this article
Cite this article
Heyne, H.O., Lemke, J.R. Die historische Entwicklung genetischer Epilepsiediagnostik. Z. Epileptol. 29, 53–56 (2016). https://doi.org/10.1007/s10309-015-0031-4
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10309-015-0031-4