Klinische FragestellungEpileptische Enzephalopathie, frühinfantil; Differentialdiagnose

NGS +

[[Sanger]]

Frühkindliche epileptische Enzephalopathie (EIEE) ist eine Anfallserkrankung mit tonischen Krämpfen innerhalb der ersten drei Lebensmonate, entweder generalisiert oder lateralisiert unabhängig vom Schlafzyklus - manchmal hunderte Male täglich. Die Spasmen können in Clustern oder einzeln auftreten und bis zu 10 Sekunden andauern. Zusätzlich treten in einem Drittel der Fälle generalisierte tonisch-klonische und fokal-motorische Anfälle sowie Hemikonvulsionen auf. Die Säuglinge entwickeln sich nicht normal mit geistiger Behinderung und sterben oft früh. Nach dem 2. Lebensjahr treten schwere psychomotorische Defizite auf. EIEE kann sich zu einem West-Syndrom (nach 2-6 Monaten) und später zu einem Lennox-Gastaut-Syndrom entwickeln. Das EEG zeigt ein kontinuierliches Suppressions-Burst Muster, das aus Bursts von Spikes mit hoher Amplitude und Polyspikes besteht, die sich mit Perioden mit niedrigem Spannungsgrundrhythmus abwechseln. Im kranialen MRT fallen häufig strukturelle Anomalien auf. Die molekulargenetische Ausbeute hängt weitgehend von der klinischen Charakterisierung ab. Ein negatives DNA-Ergebnis schließt die klinische Diagnose nicht aus.

Referenz: https://pubmed.ncbi.nlm.nih.gov/29906699/

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: Dravet Syndrome
• Alias: Early infantile epileptic encephalopathy, severe form of epilepsy
• Alias: Early-Infantile Epileptic Encephalopathy
• Allelic: Cutis laxa, AR, type IID (ATP6V1A)
• Allelic: Deafness, AD 71 (DMXL2)
• Allelic: Dystonia 9 (SLC2A1)
• Allelic: Intellectual developmental disorder with severe speech and ambulation defects (ACTL6B)
• Allelic: Intellectual developmental disorder, AR 12 (ST3GAL3)
• Allelic: Migraine, familial hemiplegic, 3 (SCN1A)
• Allelic: Polyendocrine-polyneuropathy syndrome (DMXL2)
• Allelic: Progressive external ophthalmoplegia, AD 1 (POLG)
• Allelic: Progressive external ophthalmoplegia, AR (POLG)
• Allelic: Spinocerebellar ataxia, AR 24 (UBA5)
• 3-methylglutaconic aciduria, type IX (TIMM50)
• Borjeson-Forssman-Lehmann syndrome (PHF6)
• Cornelia de Lange syndrome 2 (SMC1A)
• Developmental + epileptic encephalopathy 1 (ARX)
• Developmental + epileptic encephalopathy 1, Ohtahara syndrome (ARX1)
• Developmental + epileptic encephalopathy 15 (ST3GAL3)
• Developmental + epileptic encephalopathy 21 (NECAP1)
• Developmental + epileptic encephalopathy 38 (ARV1)
• Developmental + epileptic encephalopathy 44 (UBA5)
• Developmental + epileptic encephalopathy 46 (GRIN2D)
• Developmental + epileptic encephalopathy 47 (FGF12)
• Developmental + epileptic encephalopathy 50 (CAD)
• Developmental + epileptic encephalopathy 55 (PIGP)
• Developmental + epileptic encephalopathy 56 (YWHAG)
• Developmental + epileptic encephalopathy 57 (KCNT2)
• Developmental + epileptic encephalopathy 64 (RHOBTB2)
• Developmental + epileptic encephalopathy 65 (CYFIP2)
• Developmental + epileptic encephalopathy 66 (PACS2)
• Developmental + epileptic encephalopathy 69 (CACNA1E)
• Developmental + epileptic encephalopathy 70 (PHACTR1)
• Developmental + epileptic encephalopathy 73 (RNF13)
• Developmental + epileptic encephalopathy 73 (SIK1)
• Developmental + epileptic encephalopathy 76 (ACTL6B)
• Developmental + epileptic encephalopathy 80 (PIGB)
• Developmental + epileptic encephalopathy 81 (DMXL2)
• Developmental + epileptic encephalopathy 82 (GOT2)
• Developmental + epileptic encephalopathy 83 (UGP2)
• Developmental + epileptic encephalopathy 84 (UGDH)
• Developmental + epileptic encephalopathy 85, with/-out midline brain defects (SMC1A)
• Developmental + epileptic encephalopathy 87 (CDK19)
• Developmental + epileptic encephalopathy 90 (FGF13)
• Developmental + epileptic encephalopathy 93 (ATP6V1A)
• Epilepsy, childhood absence, susceptibility to, 2 (GABRG2)
• Epilepsy, generalized, with febrile seizures plus, type 2 (SCN1A)
• Epilepsy, generalized, with febrile seizures plus, type 3 (GABRG2)
• Epilepsy, idiopathic generalized, susceptibility to, 12 (SLC2A1)
• Epileptic encephalopathy, early infantile, 11 (SCN2A)
• Epileptic encephalopathy, early infantile, 12 (PLCB1)
• Epileptic encephalopathy, early infantile, 13 (SCN8A)
• Epileptic encephalopathy, early infantile, 14 (KCNT1)
• Epileptic encephalopathy, early infantile, 15 (ST3GAL3)
• Epileptic encephalopathy, early infantile, 16 (TBC1D24)
• Epileptic encephalopathy, early infantile, 17 (GNAO1)
• Epileptic encephalopathy, early infantile, 18 (SZT2)
• Epileptic encephalopathy, early infantile, 19 (GABRA1)
• Epileptic encephalopathy, early infantile, 2 (CDKL5)
• Epileptic encephalopathy, early infantile, 23 (DOCK7)
• Epileptic encephalopathy, early infantile, 24 (HCN1)
• Epileptic encephalopathy, early infantile, 25 (SLC13A5)
• Epileptic encephalopathy, early infantile, 26 (KCNB1)
• Epileptic encephalopathy, early infantile, 27 (GRIN2B)
• Epileptic encephalopathy, early infantile, 28 (WWOX)
• Epileptic encephalopathy, early infantile, 3 (SLC25A22)
• Epileptic encephalopathy, early infantile, 31 /DNM1)
• Epileptic encephalopathy, early infantile, 32 (KCNA2)
• Epileptic encephalopathy, early infantile, 33 (EEF1A2)
• Epileptic encephalopathy, early infantile, 34 (SLC12A5)
• Epileptic encephalopathy, early infantile, 35 (ITPA)
• Epileptic encephalopathy, early infantile, 36 (ALG13)
• Epileptic encephalopathy, early infantile, 37 (FRRS1L)
• Epileptic encephalopathy, early infantile, 38 (ARV1)
• Epileptic encephalopathy, early infantile, 39 (SLC25A12)
• Epileptic encephalopathy, early infantile, 4 (STXBP1)
• Epileptic encephalopathy, early infantile, 41 (SLC1A2)
• Epileptic encephalopathy, early infantile, 42 (CACNA1A)
• Epileptic encephalopathy, early infantile, 43 (GABRB3)
• Epileptic encephalopathy, early infantile, 44 (UBA5)
• Epileptic encephalopathy, early infantile, 46 (GRIN2D)
• Epileptic encephalopathy, early infantile, 48 (AP3B2)
• Epileptic encephalopathy, early infantile, 49 (DENND5A)
• Epileptic encephalopathy, early infantile, 5 (SPTAN)
• Epileptic encephalopathy, early infantile, 50 (CAD)
• Epileptic encephalopathy, early infantile, 51 (MDH2)
• Epileptic encephalopathy, early infantile, 52 (SCN1B)
• Epileptic encephalopathy, early infantile, 53 (SYNJ1)
• Epileptic encephalopathy, early infantile, 54 (HNRNPU)
• Epileptic encephalopathy, early infantile, 56 (YWHAG)
• Epileptic encephalopathy, early infantile, 58 (NTRK2)
• Epileptic encephalopathy, early infantile, 59 (GABBR2)
• Epileptic encephalopathy, early infantile, 6, Dravet syndrome (SCN1A)
• Epileptic encephalopathy, early infantile, 60 (CNPY3)
• Epileptic encephalopathy, early infantile, 62 (SCN3A)
• Epileptic encephalopathy, early infantile, 64 (RHOBTB2)
• Epileptic encephalopathy, early infantile, 66 (PACS2)
• Epileptic encephalopathy, early infantile, 67 (CUX2)
• Epileptic encephalopathy, early infantile, 68 (TRAK1)
• Epileptic encephalopathy, early infantile, 69 (CANA1E)
• Epileptic encephalopathy, early infantile, 7 (KCNQ2)
• Epileptic encephalopathy, early infantile, 70 (PHACTR1)
• Epileptic encephalopathy, early infantile, 73 (GABRG2)
• Epileptic encephalopathy, early infantile, 75 (PARS2)
• Epileptic encephalopathy, early infantile, 76 (ACTL6B)
• Epileptic encephalopathy, early infantile, 77 (PIGQ)
• Epileptic encephalopathy, early infantile, 78 (GABRA2)
• Epileptic encephalopathy, early infantile, 8 (ARHGEF9)
• Epileptic encephalopathy, early infantile, 80 (PIGB)
• Epileptic encephalopathy, early infantile, 9 (PCDH19)
• Febrile seizures, familial, 3A (SCN1A)
• Febrile seizures, familial, 8 (GABRG2)
• Focal segmental glomerulosclerosis + neurodevelopmental syndrome (TRIM8)
• GLUT1 deficiency syndrome 1, infantile onset, severe (SLC2A1)
• GLUT1 deficiency syndrome 2, childhood onset (SLC2A1)
• Hydranencephaly with abnormal genitalia (ARX)
• Intellectual developmental disorder, XL 29 (ARX)
• Lissencephaly, XL 2 (ARX)
• Mitochondrial DNA depletion syndrome 4A, Alpers type (POLG)
• Mitochondrial DNA depletion syndrome 4B, MNGIE type (POLG)
• Mitochondrial recessive ataxia syndrome, includes SANDO + SCAE (POLG)
• Myokymia (KCNQ2)
• Neurodevelopmental disorder with progressive microcephaly, spasticity, brain anom. (PLAA)
• Partington syndrome (ARX)
• Proud syndrome (ARX)
• Seizures, benign familial infantile, 3 (SCN2A)
• Seizures, benign neonatal, 1 (KCNQ2)
• Stomatin-deficient cryohydrocytosis with neurologic defects (SLC2A1)