IllnessEpileptic encephalopathia, early infantile; differential diagnosis

NGS +

[[Sanger]]

Early infantile epileptic encephalopathy (EIEE) is a seizure disorder with tonic spasms within the first three months, either generalized or lateralized independent of the sleep cycle – sometimes hundreds of times daily. Spasms can appear in clusters or singly and last for up to 10 seconds. Additional seizures include generalized tonic-clonic and focal motor seizures as well as hemi-convulsions in 1/3 of cases. Babies do not develop normally and even regress with intellectual disability and may die early. After age 2 severe psychomotor deficits incur. EIEE can develop into West syndrome (after 2-6 months) and later into Lennox-Gastaut syndrome. The EEG shows a continuous suppression burst pattern comprised of bursts of high amplitude spikes and poly spikes that alternate with periods of low voltage basic rhythm. Cranial MRI often displays structural abnormalities. The molecular genetic diagnostic yield depends largely on the clinical characterization. A negative DNA result does not exclude the clinical diagnosis.

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

Leitlinie: Diagnostische Prinzipien bei Epilepsien des Kindesalters; S1; From: 18.12.2017, valid until 17.12.2022; Gesellschaft für Neuropädiatrie (GNP): "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.." However GRIN2A, KCNT1, KCNQ2, KCNQ3, SCN1A genes explicitly mentioned.

• 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)