Klinische FragestellungEpilepsie, frühkindliche; Differentialdiagnose

NGS +

[Sanger]

Epilepsie kann aus einer Vielzahl von genetischen, strukturellen, metabolischen, immunologischen, infektiösen oder unbekannten Ursachen entstehen. Die meisten der anerkannten genetisch bedingten Epilepsien beginnen in der Kindheit. Zu den genetischen Epilepsien gehören die gut charakterisierten Epilepsiesyndrome der generalisierten Epilepsien, die oft mit gestörter Gehirnentwicklung und refraktären Anfällen, wie z.B. dem Dravet-Syndrom, einhergehen. Weitere infantile Epilepsiesyndrome und andere Epilepsie-Entitäten schließen fieberhafte Anfälle [plus] ein sowie die Epilepsie des Säuglingsalters mit wandernden fokalen Anfällen, West-Syndrom, myoklonische Epilepsie, gutartige familiäre infantile Epilepsie und myoklonische Enzephalopathie bei nicht-progredienten Störungen. Insgesamt sind um 100 genetisch bedingte Formen der frühkindlichen Epilepsien definiert und alle Erbgänge sind vertreten. Die Penetranzraten sind je nach mutiertem Gen niedrig bis vollständig, und die Expressivität kann teilweise ganz erheblich variieren, auch in ein und derselben Familie. Mittels DNA panel Analytik erreicht man eine Ausbeute von bis zu 25% bei Fällen mit unbekannter Ätiologie. Unauffällige Befunde schließen die klinische Diagnose daher nicht aus.

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

https://www.uptodate.com/contents/seizures-and-epilepsy-in-children-classification-etiology-and-clinical-features

Leitlinie: "Zwar haben die neuesten molekulargenetischen Befunde beigetragen, die Ursachen dieser häufigen idiopathischen Epilepsien etwas besser zu verstehen, doch ist eine routinemäßige genetische Diagnostik derzeit noch nicht sinnvoll.." GRIN2A, KCNT1, KCNQ2, KCNQ3, SCN1A Gene allerdings explizit erwähnt.

• Alias: Childhood-onset epilepsy syndrome
• Alias: Infantile spasms syndrome/West syndrome
• Allelic: Alternating hemiplegia of childhood 1 (ATP1A2)
• Allelic: Arthrogryposis, cleft palate, craniosynostosis, impaired intellectual development (PPP3CA)
• Allelic: Chilblain lupus 2 (SAMHD1)
• Allelic: Cognitive impairment with/-out cerebellar ataxia (SCN8A)
• Allelic: Cutis laxa, AR, type IID (ATP6V1A)
• Allelic: Deafness, AD 71 (DMXL2)
• Allelic: Endocrine-cerebroosteodysplasia (CI1)
• Allelic: Episodic ataxia, type 5 (CACNB4)
• Allelic: Fetal akinesia, respiratory insuff., microceph., polymicrogyria, dysmorphic face (ATP1A2)
• Allelic: Global developmental delay, progressive ataxia + elevated glutamine (GLS)
• Allelic: Hydranencephaly with abnormal genitalia (ARX)
• Allelic: Hyperaldosteronism, familial, type II (CLCN2)
• Allelic: Hyperaldosteronism, familial, type IV (CACNA1H)
• Allelic: Infantile cataract, skin abnormalities, glutamate excess, impaired intell. developm. (GLS)
• Allelic: Intellectual developmental disorder, AR 12 (ST3GAL3)
• Allelic: Migraine, familial basilar (ATP1A2)
• Allelic: Migraine, familial hemiplegic, 2 (ATP1A2)
• Allelic: Neuropathy, hereditary sensory + autonomic, type IID (SCN9A)
• Allelic: Obesity, hyperphagia + developmental delay (NTRK2)
• Allelic: Paroxysmal nocturnal hemoglobinuria 2 (PIGT)
• Allelic: Paroxysmal nocturnal hemoglobinuria, somatic (PIGA)
• Allelic: Polyendocrine-polyneuropathy syndrome (DMXL2)
• Allelic: Progressive external ophthalmoplegia, AD 1/AR 1 (POLG)
• Allelic: Small fiber neuropathy (SCN9A)
• Allelic: Spinocerebellar ataxia, AR 12 (WWOX)
• Allelic: Spinocerebellar ataxia, AR 24 (UBA5)
• Allelic: Usher syndrome, type 2C (ADGRV1)
• Aicardi-Goutieres syndrome 1, AD/AR (TREX1)
• Aicardi-Goutieres syndrome 2 (RNASEH2B)
• Aicardi-Goutieres syndrome 3 (RNASH2C)
• Aicardi-Goutieres syndrome 4 (RNASH2A)
• Aicardi-Goutieres syndrome 5 (SAMHD1)
• Aicardi-Goutieres syndrome 6 (ADAR1)
• Aicardi-Goutieres syndrome 7 (IFIH1)
• Cerebellar atrophy, developmental delay + seizures (KCNMA1)
• Ceroid lipofuscinosis, neuronal, 1 (PPT1)
• Ceroid lipofuscinosis, neuronal, 10 (CTSD)
• Ceroid lipofuscinosis, neuronal, 11 (GRN)
• Ceroid lipofuscinosis, neuronal, 13 (Kufs type), AD (CTSF)
• Ceroid lipofuscinosis, neuronal, 2 (TPP1)
• Ceroid lipofuscinosis, neuronal, 3 (CLN3)
• Ceroid lipofuscinosis, neuronal, 4, Kufs type (DNAJC5)
• Ceroid lipofuscinosis, neuronal, 5 (CLN5)
• Ceroid lipofuscinosis, neuronal, 6A (CLN6)
• Ceroid lipofuscinosis, neuronal, 6B, Kufs type (CLN6)
• Ceroid lipofuscinosis, neuronal, 7 (MFSD8)
• Ceroid lipofuscinosis, neuronal, 8 (CLN8)
• Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant (CLN8)
• Chromosome 5q14.3 deletion syndrome (MEF2C)
• Cone-rod synaptic disorder, congenital nonprogressive (CABP4)
• Congenital disorder of glycosylation, type IIm (SLC35A2)
• Convulsions, familial infantile, with paroxysmal choreoathetosis (PRRT2)
• Cornelia de Lange syndrome 2 (SMC1A)
• Cortical dysplasia-focal epilepsy syndrome (CNTNAP2)
• DOORS syndrome (TBC1D24)
• Developmental + epileptic encephalopathy 1 (ARX)
• Developmental + epileptic encephalopathy 103 (KCNC2)
• Developmental + epileptic encephalopathy 12 (PLCB1)
• Developmental + epileptic encephalopathy 13 (SCN8A)
• Developmental + epileptic encephalopathy 14 (KCNT1)
• Developmental + epileptic encephalopathy 15 (ST3GAL3)
• Developmental + epileptic encephalopathy 16 (TBC1D24)
• Developmental + epileptic encephalopathy 17 (GNAO1)
• Developmental + epileptic encephalopathy 18 (SZT2)
• Developmental + epileptic encephalopathy 19 (GABRA1)
• Developmental + epileptic encephalopathy 21 (NECAP1)
• Developmental + epileptic encephalopathy 23 (DOCK7)
• Developmental + epileptic encephalopathy 24 (HCN1)
• Developmental + epileptic encephalopathy 25, with amelogenesis imperfecta (SLC13A5)
• Developmental + epileptic encephalopathy 26 (KCNB1)
• Developmental + epileptic encephalopathy 27 (GRIN2B)
• Developmental + epileptic encephalopathy 28 (WWOX)
• Developmental + epileptic encephalopathy 29 (AARS1)
• Developmental + epileptic encephalopathy 31 (DNM1)
• Developmental + epileptic encephalopathy 32 (KCNA2)
• Developmental + epileptic encephalopathy 33 (EEF1A2)
• Developmental + epileptic encephalopathy 34 (SLC12A5)
• Developmental + epileptic encephalopathy 35 (ITPA)
• Developmental + epileptic encephalopathy 36 (ALG13)
• Developmental + epileptic encephalopathy 37 (FRRS1L)
• Developmental + epileptic encephalopathy 38 (ARV1)
• Developmental + epileptic encephalopathy 39 (SLC25A12)
• Developmental + epileptic encephalopathy 41 (SLC1A2)
• Developmental + epileptic encephalopathy 42 (CACNA1A)
• Developmental + epileptic encephalopathy 44 (UBA5)
• Developmental + epileptic encephalopathy 46 (GRIN2D)
• Developmental + epileptic encephalopathy 47 (FGF12)
• Developmental + epileptic encephalopathy 48 (AP3B2)
• Developmental + epileptic encephalopathy 49 (DENND5A)
• Developmental + epileptic encephalopathy 5 (SPTAN1)
• Developmental + epileptic encephalopathy 51 (MDH2)
• Developmental + epileptic encephalopathy 52 (SCN1B)
• Developmental + epileptic encephalopathy 53 (SYNJ1)
• Developmental + epileptic encephalopathy 54 (HNRNPU)
• Developmental + epileptic encephalopathy 56 (YWHAG)
• Developmental + epileptic encephalopathy 57 (KCNT2)
• Developmental + epileptic encephalopathy 58 (NTRK2)
• Developmental + epileptic encephalopathy 59 (GABBR2)
• Developmental + epileptic encephalopathy 60 (CNPY3)
• Developmental + epileptic encephalopathy 62 (SCN3A)
• Developmental + epileptic encephalopathy 64 (RHOBTB2)
• Developmental + epileptic encephalopathy 65 (CYFIP2)
• Developmental + epileptic encephalopathy 66 (PACS2)
• Developmental + epileptic encephalopathy 67 (CUX2)
• Developmental + epileptic encephalopathy 68 (TRAK1)
• Developmental + epileptic encephalopathy 69 (CACNA1E)
• Developmental + epileptic encephalopathy 7 (KCNQ2)
• Developmental + epileptic encephalopathy 70 (PHACTR1)
• Developmental + epileptic encephalopathy 71 (GLS)
• Developmental + epileptic encephalopathy 75 (PARS2)
• Developmental + epileptic encephalopathy 76 (ACTL6B)
• Developmental + epileptic encephalopathy 77 (PIGQ)
• Developmental + epileptic encephalopathy 78 (GABRA2)
• Developmental + epileptic encephalopathy 79 (GABRA5)
• Developmental + epileptic encephalopathy 8 (ARHGEF9)
• Developmental + epileptic encephalopathy 80 (PIGB)
• Developmental + epileptic encephalopathy 81 (DMXL2)
• Developmental + epileptic encephalopathy 82 (GOT2)
• Developmental + epileptic encephalopathy 85, with/-out midline brain defects (SMC1A)
• Developmental + epileptic encephalopathy 89 (GAD1)
• Developmental + epileptic encephalopathy 90 (FGF13)
• Developmental + epileptic encephalopathy 91 (PPP3CA)
• Developmental + epileptic encephalopathy 92 (GABRB2)
• Developmental + epileptic encephalopathy 93 (ATP6V1A)
• Developmental + epileptic encephalopathy 94 (CHD2)
• Developmental + epileptic encephalopathy 98 (ATP1A2)
• Developmental + epileptic encephalopathy 99 (ATP1A3)
• Dicarboxylic aminoaciduria (SLC1A1)
• Dystonia 9 (SLC2A1)
• Encephalopathy, familial, with neuroserpin inclusion bodies (SERPINI1)
• Encephalopathy, neonatal severe (MECP2)
• Enlarged vestibular aqueduct, digenic (KCNJ10)
• Epilepsy nocturnal frontal lobe, 5 (KCNT1)
• Epilepsy, childhood absence [Lit.] (JRK)
• Epilepsy, childhood absence, susceptibility to, 2 (GABRG2)
• Epilepsy, childhood absence, susceptibility to, 6 (CACNNA1H)
• Epilepsy, familial focal, with variable foci 1 (DDEPDC5)
• Epilepsy, familial focal, with variable foci 2 (NPRL2)
• Epilepsy, familial focal, with variable foci 3 (NPRL3)
• Epilepsy, familial focal, with variable foci 4 (SCN3A)
• Epilepsy, familial temporal lobe, 1 (LGI1)
• Epilepsy, familial temporal lobe, 5 (CPA6)
• Epilepsy, familial temporal lobe, 7 (RELN)
• Epilepsy, focal, with speech disorder with/-out impaired intellectual development (GRIN2A)
• Epilepsy, generalized, with febrile seizures plus, type 2 (SCN1A)
• Epilepsy, generalized, with febrile seizures plus, type 3 (GABRG2)
• Epilepsy, idiopathic generalized, 10 (GABRD)
• Epilepsy, idiopathic generalized, susceptibility to, 11 (CLCN2)
• 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, 6 (CACNA1H)
• Epilepsy, idiopathic generalized, susceptibility to, 9 (CACNB4)
• Epilepsy, juvenile absence, susceptibility to, 1 (EFHC1)
• Epilepsy, juvenile absence, susceptibility to, 2 (CLCN2)
• Epilepsy, juvenile myoclonic, susceptibility to (GABRD)
• Epilepsy, juvenile myoclonic, susceptibility to, 10 (CILK1)
• Epilepsy, juvenile myoclonic, susceptibility to, 6 (CACNB4)
• Epilepsy, juvenile myoclonic, susceptibility to, 8 (CLCN2)
• Epilepsy, nocturnal frontal lobe, 1 (CHRNA4)
• Epilepsy, nocturnal frontal lobe, 3 (CHRNB2)
• Epilepsy, nocturnal frontal lobe, type 4 (CHRNA2)
• Epilepsy, progressive myoclonic 1A, Unverricht and Lundborg (CSTB)
• Epilepsy, progressive myoclonic 1B (PRICKLE1)
• Epilepsy, progressive myoclonic 2A, Lafora (EPM2A)
• Epilepsy, progressive myoclonic 2B, Lafora (NHLRC1)
• Epilepsy, progressive myoclonic 3, with/-out intracellular inclusions (KCTD7)
• Epilepsy, progressive myoclonic 4, with/-out renal failure (SCARB2)
• Epilepsy, progressive myoclonic 6 (GOSR2)
• Epilepsy, progressive myoclonic 7 (KCNC1)
• Epilepsy, progressive myoclonic, 10 (PRDM8)
• Epilepsy, progressive myoclonic, 8 (CERS1)
• Epilepsy, progressive myoclonic, 9 (LMNB2)
• Epilepsy, pyridoxine-dependent (ALDH7A1)
• Epilepsy, rolandic, with proxysmal exercise-induce dystonia + writer's cramp (TBC1D24)
• Epileptic encephalopathy Lennox-Gastaut type [panelapp] (MAPK10)
• Epileptic encephalopathy, early infantile, 11 (SCN2A)
• Epileptic encephalopathy, early infantile, 2 (CDKL5)
• Epileptic encephalopathy, early infantile, 3 (SLC25A22)
• Epileptic encephalopathy, early infantile, 4 (STXBP1)
• Epileptic encephalopathy, early infantile, 6 [Dravet syndrome] (SCN1A)
• Epileptic encephalopathy, early infantile, 74 (GABRG2)
• Epileptic encephalopathy, early infantile, 9 (GABRG2)
• Episodic ataxia, type 9 (SCN2A)
• Episodic kinesigenic dyskinesia 1 (PRRT2)
• Farber lipogranulomatosis (ASAH1)
• Febrile seizures, familial, 11 (CPA6)
• Febrile seizures, familial, 2 (HCN2)
• Febrile seizures, familial, 3A (SCN1A)
• Febrile seizures, familial, 4 (ADGRV1)
• Febrile seizures, familial, 8 (GABRG2)
• GLUT1 deficiency syndrome 1, infantile onset, severe (SLC2A1)
• GLUT1 deficiency syndrome 2, childhood onset (SLC2A1)
• Generalized epilepsy with febrile seizures plus, type 1 (SCN1B)
• 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 5, susceptibility to (GABRD)
• Generalized epilepsy with febrile seizures plus, type 9 (STX1B)
• Insensitivity to pain, congenital (SCN9A)
• Intellectual developmental disorder 60 with seizures (AP2M1)
• Intellectual developmental disorder with severe speech + ambulation defects (ACTL6B)
• Intellectual developmental disorder, AD 6, with/-out seizures (GRIN2B)
• Intellectual developmental disorder, XL 29 (ARX)
• Intellectual developmental disorder, XL 98 (NEXMIF)
• Intellectual developmental disorder, XL syndromic, Christianson type (SLC9A6)
• Intellectual developmental disorder, XL syndromic, Lubs type (MECP2)
• Intellectual developmental disorder, XL syndromic, Snyder-Robinson type (SMS)
• Intellectual developmental disorder, XL, syndromic 13 (MECP2)
• Intractable infantile spasms [Lit.] (CRH)
• Lacticacidemia due to PDX1 deficiency (PDHX)
• Leukoencephalopathy with ataxia (CLCN2)
• Liang-Wang syndrome (KCNMA1)
• Lissencephaly 1 (PAHFA1B1)
• Lissencephaly 2, Norman-Roberts type (RELN)
• Lissencephaly, XL (DCX)
• Lissencephaly, XL 2 (ARX)
• Mental retardation, AD 1 (MBD5)
• Mental retardation, AD 38 (EEF1A2)
• Mental retardation, AD 5 (SYNGAP1)
• Mental retardation, AD 7 (DYRK1A)
• Microcephaly, epilepsy + diabetes syndrome (IER3IP1)
• Microcephaly, seizures + developmental delay (PNKP)
• Migraine, familial hemiplegic, 3 (SCN1A)
• Mitochondrial DNA depletion syndrome 4A, Alpers type (POLG)
• Mitochondrial DNA depletion syndrome 4B, MNGIE type (POLG)
• Mitochondrial recessive ataxia syndrome, includes SANDO + SCAE (POLG)
• Multiple congenital anomalies-hypotonia-seizures syndrome 1 (PIGN)
• Multiple congenital anomalies-hypotonia-seizures syndrome 2 (PIGA)
• Multiple congenital anomalies-hypotonia-seizures syndrome 3 (PIGT)
• Myoclonic epilepsy, infantile, familial (TBC1D24)
• Myoclonic epilepsy, juvenile, susceptibility to, 1 (EFHC1)
• Myoclonic-atonic epilepsy (SLC6A1)
• Myoclonus, familial, 2 (SCN8A)
• Myokymia (KCNQ2)
• Neurodegeneration due to cerebral folate transport deficiency (FOLR1)
• Neurodevelopmental delay, behavioral difficulties + epilepsy [Lit.] (PRICKLE2)
• Neurodevelopmental disorder with hypotonia, stereotypic hand movements, impaired language (MEF2C)
• Neurodevelopmental disorder with involuntary movements (GNAO1)
• Neurodevelopmental disorder with/-out hyperkinetic movements + seizures, AD/AR (GRIN1)
• Parkinson disease 20, early-on (SYNJ1)
• Paroxysmal extreme pain disorder (SCN9A)
• Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy (KCNMA1)
• Partington syndrome (ARX)
• Pitt-Hopkins syndrome (TCF4)
• Pitt-Hopkins-like syndrome 1 (CNTNAP2)
• Pitt-Hopkins-like syndrome 2 (NRXN1)
• Proud syndrome (ARX)
• Pseudo-TORCH syndrome 1 (OCLN)
• Pyridoxamine 5'-phosphate oxidase deficiency (PNPO)
• Rett syndrome (MECP2)
• Rett syndrome, atypical (MECP2)
• Rett syndrome, congenital variant (FOXG1)
• Rett syndrome, preserved speech variant (MECP2)
• Rolandic epilepsy, impaired intellectual development + speech dyspraxia (SRPX2)
• SESAME syndrome (KCNJ10)
• Salt + pepper developmental regression syndrome (ST3GAL5)
• Seizures, benign familial infantile, 2 (PRRT2)
• Seizures, benign familial infantile, 3 (SCN2A)
• Seizures, benign familial infantile, 5 (SCN8A)
• Seizures, benign neonatal, 1 (KCNQ2)
• Seizures, benign neonatal, 2 (KCNQ3)
• Singleton-Merten syndrome 1 (IFIH1)
• Spinal muscular atrophy with progressive myoclonic epilepsy (ASAH1)
• Stomatin-deficient cryohydrocytosis with neurologic defects (SLC2A1)
• Subcortical laminal heterotopia, XL (DCX)
• Subcortical laminar heterotopia (PAHFA1B1)