Klinische FragestellungEpilepsie, generalisierte idiopathische, Erwachsene; Differentialdiagnose

NGS +

Generalisierte idiopathische Epilepsien oder genetische generalisierte Epilepsien sind eine Gruppe von Syndromen, die durch Anfälle mit nicht-fokalen Entstehungsmechanismen wie Absencen, myoklonischen oder primär generalisierten tonisch-klonischen Anfällen und typischen EEG-Befunden (generalisierte spike-wave Entladungen, provoziert durch Hyperventilation oder Licht-Stimulation) gekennzeichnet sind. Es besteht eine diffuse kortikale und subkortikale Übererregbarkeit, insbesondere in thalamokortikalen Schaltkreisen. Diese Epilepsie-Formen treten bei ansonsten gesunden Personen ohne erkennbare Ursache (außer einer genetischen Veranlagung) auf. Die meisten dieser Syndrome beginnen in der Kindheit, einige erst im Erwachsenenalter. Die häufigsten IGE-Syndrome sind Absence-Epilepsie in der Kindheit, juvenile Absence-Epilepsie, juvenile myoklonische Epilepsie und isolierte generalisierte Epilepsie mit generalisierten tonisch-klonischen Anfällen. Die diesen Epilepsie-Syndromen zugrundeliegenden molekulargenetischen Ursachen werden erst langsam zunehmend besser charakterisiert, der Erbgang ist oft autosomal dominant, selten rezessiv oder X-chromosomal. Die DNA-diagnostische Ausbeute liegt in dieser Kategorie wenig über 5%, sodass unauffällige genetische Befunde keinerlei Ausschluss der klinischen Verdachtsdiagnosen bedeuten.

Referenzen: https://www.ncbi.nlm.nih.gov/books/NBK1318/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369901/

• Alias: Idiopathic or cryptogenic familial epilepsy syndrome with identified loci/genes
• Allelic: Achondroplasia (FGFR3)
• Allelic: Atrial fibrillation, familial, 13 (SCN1B)
• Allelic: Brugada syndrome 5 (SCN1B)
• Allelic: CATSHL syndrome (FGFR3)
• Allelic: Cardiac conduction defect, nonspecific (SCN1B)
• Allelic: Charcot-Marie-Tooth disease, axonal, type 20 (DYNC1H1)
• Allelic: Crouzon syndrome with acanthosis nigricans (FGFR3)
• Allelic: DOORS [deafness, onychodystr., osteodystr., MR, seizures] syndrome (TBC1D24)
• Allelic: Developmental and epileptic encephalopathy 34 (SLC12A5)
• Allelic: Dystonia 9 (SLC2A1)
• Allelic: Epilepsy, familial temporal lobe, 5 (CPA6)
• Allelic: Epilepsy, juvenile myoclonic, susceptibility to (GABRD)
• Allelic: Epilepsy, juvenile myoclonic, susceptibility to, 6 (CACNB4)
• Allelic: Epilepsy, rolandic, with paroxysmal exercise-induce dystonia and writer's cramp (TBC1D24)
• Allelic: Episodic ataxia, type 2 (CACNA1A)
• Allelic: Episodic ataxia, type 5 (CACNB4)
• Allelic: Episodic ataxia, type 9 (SCN2A)
• Allelic: Erythermalgia, primary (SCN9A)
• Allelic: Generalized epilepsy with febrile seizures plus, type 5, susceptibility to (GABRD)
• Allelic: Hypochondroplasia (FGFR3)
• Allelic: Insensitivity to pain, congenital (SCN9A)
• Allelic: LADD syndrome (FGFR3)
• Allelic: Lymphangioleiomyomatosis (TSC1)
• Allelic: Muenke syndrome (FGFR3)
• Allelic: Neuropathy, hereditary sensory and autonomic, type IID (SCN9A)
• Allelic: Paroxysmal extreme pain disorder (SCN9A)
• Allelic: Seizures, benign familial infantile, 3 (SCN2A)
• Allelic: Small fiber neuropathy (SCN9A)
• Allelic: Spinal muscular atrophy, lower extremity-predominant 1, AD (DYNC1H1)
• Allelic: Spinocerebellar ataxia 6 (CACNA1A)
• Cerebellar atrophy, developmental delay, seizures (KCNMA1)
• Ceroid lipofuscinosis, neuronal, 4, Parry type (DNAJC5)
• Cornelia de Lange syndrome 2 (SMC1A)
• D-2-hydroxyglutaric aciduria (D2HGDH)
• Deafness, autosomal dominant 65 616044 AD 3
• Deafness, autosomal recessive 86 614617 AR 3
• Developmental + epileptic encephalopathy 11 (SCN2A)
• Developmental + epileptic encephalopathy 14 (KCNT1)
• Developmental + epileptic encephalopathy 16 (TBC1D24)
• Developmental + epileptic encephalopathy 19 (GABRA1)
• Developmental + epileptic encephalopathy 24 (HCN1)
• Developmental + epileptic encephalopathy 26 (KCNB1)
• Developmental + epileptic encephalopathy 4 (STXBP1)
• Developmental + epileptic encephalopathy 42 (CACNA1A)
• Developmental + epileptic encephalopathy 85, with/-out midline brain defects (SMC1A)
• Developmental + epileptic encephalopathy 94 (CHD2)
• Epilepsy nocturnal frontal lobe, 5 (KCNT1)
• Epilepsy, childhood absence, susceptibility to, 4 (GABRA1)
• Epilepsy, generalized, with febrile seizures plus, type 1 (SCN1B)
• Epilepsy, generalized, with febrile seizures plus, type 2 (SCN1A)
• Epilepsy, generalized, with febrile seizures plus, type 3 (GABRG2)
• Epilepsy, generalized, with febrile seizures plus, type 7 (SCN9A)
• Epilepsy, idiopathic generalized, 10 (GABRD)
• Epilepsy, idiopathic generalized, susceptibility to, 12 (SLC2A1)
• Epilepsy, idiopathic generalized, susceptibility to, 14 (SLC12A5)
• Epilepsy, idiopathic generalized, susceptibility to, 15 (RORB)
• Epilepsy, idiopathic generalized, susceptibility to, 16 (KCNMA1)
• Epilepsy, idiopathic generalized, susceptibility to, 17 (HCN2)
• Epilepsy, idiopathic generalized, susceptibility to, 9 (CACNB4)
• Epilepsy, juvenile myoclonic, susceptibility to, 5 (GABRA1)
• Epileptic encephalopathy, early infantile, 52 (SCN1B)
• Epileptic encephalopathy, early infantile, 6 [Dravet syndrome] (SCN1A)
• Epileptic encephalopathy, early infantile, 7 (KCNQ2)
• Epileptic encephalopathy, early infantile, 74 (GABRG2)
• Febrile seizures, familial, 11 (CPA6)
• Febrile seizures, familial, 2 (HCN2)
• Febrile seizures, familial, 3A (SCN1A)
• Febrile seizures, familial, 8 (GABRG2)
• Focal cortical dysplasia, type II, somatic (TSC1)
• GLUT1 deficiency syndrome 1, infantile onset, severe (SLC2A1)
• GLUT1 deficiency syndrome 2, childhood onset (SLC2A1)
• Generalized epilepsy with febrile seizures plus, type 10 (HCN1)
• Generalized epilepsy with febrile seizures plus, type 11 (HCN2)
• Generalized epilepsy with febrile seizures plus, type 9 (STX1B)
• Intellectual developmental disorder, XL syndromic 34 (NONO)
• KBG syndrome (ANKRD11)
• Kufs Disease, AD (DNAJC5)
• Liang-Wang syndrome (KCNMA1)
• Lissencephaly 1 (PAFAH1B1)
• Lissencephaly, XL (DCX)
• Megalencephalic leukoencephalopathy with subcortical cysts (MLC1)
• Mental retardation, AD 1 (MBD5)
• Mental retardation, AD 13 (DYNC1H1)
• Mental retardation, AD 31 (PURA)
• Mental retardation, AR 41 (KPTN)
• Migraine, familial hemiplegic, 1 (CACNA1A)
• Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia (CACNA1A)
• Migraine, familial hemiplegic, 3 (SCN1A)
• Myoclonic epilepsy, infantile, familial (TBC1D24)
• Myokymia Seizures, benign neonatal, 1 (KCNQ2)
• Paroxysmal nonkinesigenic dyskinesia, 3, with/-out generalized epilepsy (KCNMA1)
• SADDAN (FGFR3)
• Stomatin-deficient cryohydrocytosis with neurologic defects (SLC2A1)
• Subcortical laminal heterotopia, XL (DCX)
• Subcortical laminar heterotopia (PAFAH1B1)
• Succinic semialdehyde dehydrogenase deficiency (ALDH5A1)
• Tuberous sclerosis-1 (TSC1)