Klinische FragestellungMentale Retardierung bei Epilepsie/Enzephalopathie, Differentialdiagnose

NGS +

Da Komorbiditäts-Epilepsie häufig bei Patienten mit geistiger Behinderung auftritt, ist sie mit einer Gesamtprävalenz von ~26% die häufigste schwere medizinische Erkrankung in dieser klinischen Gruppe.

Leitlinie: Diagnostische Prinzipien bei Epilepsien des Kindesalters; S1; Stand: 18.12.2017, gültig bis 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.." GRIN2A, KCNT1, KCNQ2, KCNQ3, SCN1A Gene allerdings explizit erwähnt.

• Alias: Intellectual disability + epilepsy
• Alias: Psycho-motor retardation + epilepsy
• Allelic: Cardiomyopathy, dilated, 1X (FKTN)
• Allelic: Charcot-Marie-Tooth disease, axonal, type 2DD (ATP1A1)
• Allelic: Charcot-Marie-Tooth disease, axonal, type 2O (DYNC1H1)
• Allelic: Dentatorubral-pallidoluysian atrophy (ATN1_CAG)
• Allelic: Dyschromatosis symmetrica hereditaria (ADAR)
• Allelic: Epilepsy, generalized, with febrile seizures plus, type 2 (SCN1A)
• Allelic: Febrile seizures, familial, 3A (SCN1A)
• Allelic: Hemorrhage, intracerebral, susceptibility to (COL4A1)
• Allelic: Migraine, familial hemiplegic, 3 (SCN1A)
• Allelic: Muscular dystrophy-dystroglycanopathy, cong. without mental retardation), type B, 4 (FKTN)
• Allelic: Neuropathy, distal hereditary motor, type VC (BSCL2)
• Allelic: Optic atrophy 5 (DNM1L)
• Allelic: Polycystic liver disease 3 with or without kidney cysts (ALG8)
• Allelic: Retinal arteries, tortuosity of (COL4A1)
• Allelic: Retinitis pigmentosa 93 (CC2D2A)
• 3-methylglutaconic aciduria, type VIII (HTRA2)
• 5-fluorouracil toxicity (DPYD)
• Adenylosuccinase deficiency (ADSL)
• Aicardi-Goutieres syndrome 6 (ADAR)
• Aicardi-Goutieres syndrome 7 (IFIH1)
• Alexander disease (GFAP)
• Alkuraya-Kucinskas syndrome (BLTP1)
• Allelic: Autism susceptibility, XL 3 (MECP2)
• Allelic: Diabetes mellitus, transient neonatal 3 (KCNJ11)
• Allelic: Diabetes mellitus, type 2, susceptibility to (KCNJ11)
• Allelic: Ectodermal dysplasia + immunodeficiency 1 (IKBKG)
• Allelic: Immunodeficiency 33 (IKBKG)
• Allelic: Immunodeficiency 95 (IFIH1)
• Allelic: Maturity-onset diabetes of the young, type 13 (KCNJ11)
• Allelic: Neuropathy, hereditary sensory, type IIC (KIF1A)
• Allelic: Parkinson disease 13 (HTRA2)
• Allelic: Perrault syndrome 1 (HSD17B4)
• Allelic: RAS-associated autoimmune leukoproliferative disorder (KRAS)
• Allelic: Skin/hair/eye pigmentation 1, blond/brown hair (HERC2)
• Allelic: Skin/hair/eye pigmentation 1, blue/nonblue eyes (HERC2)
• Alpha-thalassemia/mental retardation syndrome (ATRX)
• Alternating hemiplegia of childhood 1 (ATP1A2)
• Alternating hemiplegia of childhood 2 (ATP1A3)
• Angiopathy, hereditary, with nephropathy, aneurysms + muscle cramps (COL4A1)
• Argininemia (ARG1)
• Aromatic L-amino acid decarboxylase deficiency (DDC)
• Asparagine synthetase deficiency (ASNS)
• Autoinflammatory disease, systemic, XL (IKBKG)
• Ayme-Gripp syndrome (MAF)
• Biotinidase deficiency (BTD)
• Bjornstad syndrome (BCS1L)
• Brain small vessel disease with/-out ocular anomalies (COL4A1)
• Bryant-Li-Bhoj neurodevelopmental syndrome 2 (H3F3B)
• CAPOS [Cereb. ataxia, Areflexia, Pes cavus, Optic atrophy, Sensorineural deaf] syndrome (ATP1A3)
• COACH syndrome 2 (CC2D2A)
• Canavan disease (ASPA)
• Cardiofaciocutaneous syndrome (BRAF)
• Cardiofaciocutaneous syndrome 2 (KRAS)
• Cardiofaciocutaneous syndrome 3 (MAP2K1)
• Cerebellar atrophy, developmental delay + seizures (KCNMA1)
• Cerebral creatine deficiency syndrome 2 (GAMT)
• Ceroid lipofuscinosis, neuronal, 10 (CTSD)
• Ceroid lipofuscinosis, neuronal, 3 (CLN3)
• Coenzyme Q10 deficiency, primary, 7 (COQ4)
• Coffin-Siris syndrome 1 (ARID1B)
• Combined oxidative phosphorylation deficiency 12 (EARS2)
• Combined oxidative phosphorylation deficiency 14 (FARS2)
• Congenital disorder of glycosylation with defective fucosylation 1 (FUT8)
• Congenital disorder of glycosylation, type IIe (COG7)
• Congenital disorder of glycosylation, type IIf (SLC35A1)
• Congenital disorder of glycosylation, type IIt (GALNT2)
• Congenital disorder of glycosylation, type Ic (ALG6)
• Congenital disorder of glycosylation, type Id (ALG3)
• Congenital disorder of glycosylation, type Ie (DPM1)
• Congenital disorder of glycosylation, type Ih (ALG8)
• Congenital disorder of glycosylation, type Ij (DPAGT1)
• Congenital disorder of glycosylation, type Ik (ALG1)
• Congenital disorder of glycosylation, type Il (ALG9)
• Congenital disorder of glycosylation, type Ip (ALG11)
• Congenital hypotonia, epilepsy, developmental delay + digital anomalies (ATN1)
• Congenital myopathy with excess of muscle spindles (HRAS)
• Cortical dysplasia, complex, with other brain malformations 10 (APC2)
• Cortical dysplasia, complex, with other brain malformations 2 (KIF5C)
• Cortical dysplasia, complex, with other brain malformations 3 (KIF2A)
• Cortical dysplasia, complex, with other brain malformations 9 (CTNNA2)
• Costello syndrome (HRAS)
• Cutis laxa, AR, type IIA (ATP6V0A2)
• D-2-hydroxyglutaric aciduria (D2HGDH)
• D-bifunctional protein deficiency (HSD17B4)
• DEEAH [developm. delay + endocrine, exocrine, autonomic + hematologic abnormalities] syndrome (MADD)
• Developmental + epileptic encephalopathy 1 (ARX)
• Developmental + epileptic encephalopathy 44 (UBA5)
• Developmental + epileptic encephalopathy 46 (GRIN2D)
• Developmental + epileptic encephalopathy 47 (FGF12)
• Developmental + epileptic encephalopathy 50 (CAD)
• 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 80 (PIGB)
• Developmental + epileptic encephalopathy 89 (GAD1)
• Developmental + epileptic encephalopathy 92 (GABRB2)
• Developmental + epileptic encephalopathy 93 (ATP6V1A)
• Developmental + epileptic encephalopathy 98 (ATP1A2)
• Developmental + epileptic encephalopathy 99 (ATP1A3)
• Developmental delay + seizures with/-out movement abnormalities (DHDDS)
• Developmental delay with variable neurologic + brain abnormalities (LMBRD2)
• Developmental delay with/-out dysmorphic facies + autism (TRRAP)
• Developmental epileptic encephalopathy [panelapp] (KCTD3)
• Diabetes, permanent neonatal 2, with/-out neurologic features (KCNJ11)
• Diencephalic-mesencephalic junction dysplasia syndrome 1 (PCDH12)
• Dihydropyrimidine dehydrogenase deficiency (DPYD)
• Dystonia-12 (ATP1A3)
• Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 (DNM1L)
• Encephalopathy, neonatal severe (MECP2)
• Encephalopathy, progressive, with/-out lipodystrophy (BSCL2)
• Epilepsy, XL, with variable learning disabilities + behavior disorders (SYN1)
• Epilepsy, early-onset, vitamin B6-dependent (PLPBP)
• Epilepsy, focal, with speech disorder + with/-out mental retardation (GRIN21A)
• Epilepsy, hearing loss + mental retardation syndrome (SPATA5)
• Epilepsy, idiopathic generalized, 10 (GABRD)
• Epilepsy, idiopathic generalized, susceptibility to, 16 (KCNMA1)
• Epilepsy, juvenile myoclonic, susceptibility to (GABRD)
• Epilepsy, progressive myoclonic 1A, Unverricht + Lundborg (CSTB)
• Epileptic encephalopathy, early infantile, 1 (ARX)
• 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, 21 (NECAP1)
• Epileptic encephalopathy, early infantile, 3 (SLC25A22)
• Epileptic encephalopathy, early infantile, 4 (STXBP1)
• Epileptic encephalopathy, early infantile, 5 (SPTAN1)
• Epileptic encephalopathy, early infantile, 6 [Dravet syndrome] (SCN1A)
• Epileptic encephalopathy, early infantile, 7 (KCNQ2)
• Epileptic encephalopathy, early infantile, 8 (ARHGEF9)
• Epileptic encephalopathy, early infantile, 9 (PCDH19)
• Epileptic encephalopathy, infantile or early childhood, 1 (PPP3CA)
• Epileptic encephalopathy, infantile or early childhood, 2 (GABRB2)
• Epileptic encephalopathy, infantile or early childhood, 3 (ATP6V1A)
• Ethylmalonic encephalopathy (ETHE1)
• FG syndrome 4 (CASK)
• Farber lipogranulomatosis (ASAH1)
• Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria + dysmorphic facies (ATP1A2)
• Focal segmental glomerulosclerosis + neurodevelopmental syndrome (TRIM8)
• Fucosidosis (FUCA1)
• GABA-transaminase deficiency (ABAT)
• GM1-gangliosidosis, type I, II, III (GLB1)
• GM2-gangliosidosis, AB variant (GM2A)
• GM2-gangliosidosis, several forms (HEXA)
• GRACILE syndrome (BCS1L)
• Generalized epilepsy with febrile seizures plus, type 5, susceptibility to (GABRD)
• Gillessen-Kaesbach-Nishimura syndrome (ALG9)
• Global developmental delay, seizures, microcephaly, short digit [no OMIM] (HNRNPR)
• Glutamine deficiency, congenital (GLUL)
• Glycine encephalopathy (AMT)
• Glycine encephalopathy (GLDC)
• Glycosylphosphatidylinositol biosynthesis defect 15 (GPAA1)
• HMG-CoA lyase deficiency (HMGCL)
• Hardikar syndrome (MED12)
• Hex A pseudodeficiency (HEXA)
• Hiatt-Neu-Cooper neurodevelopmental syndrome (RALA)
• Hydranencephaly with abnormal genitalia (ARX)
• Hyperglycinemia, lactic acidosis + seizures (LIAS)
• Hyperinsulinemic hypoglycemia, familial, 2 (KCNJ11)
• Hypomagnesemia, seizures + mental retardation (CNNM2)
• Hypomagnesemia, seizures + mental retardation 2 (ATP1A1)
• Hypotonia, hypoventilation, impaired intell. devel., dysautonomia, epilepsy, eye abnorm. (P4HTM)
• Hypotonia, hypoventilation, impaired intell. develop., dysautonomia, epilepsy, eye abnorm. (P4HTM)
• Incontinentia pigmenti (IKBKG)
• Infantile liver failure syndrome 1 (LARS1)
• Intellectual developmental disorder + microcephaly with pontine + cerebellar hypoplasia (CASK)
• Intellectual developmental disorder 60 with seizures (AP2M1)
• Intellectual developmental disorder with cardiac arrhythmia (GNB5)
• Intellectual developmental disorder with dysmorphic facies + behavioral abnormalities (FBXO11)
• Intellectual developmental disorder, AD 1 (MBD5)
• Intellectual developmental disorder, AD 13 (DYNC1H1)
• Intellectual developmental disorder, AD 42 (GNB1)
• Intellectual developmental disorder, AD 45 (CIC)
• Intellectual developmental disorder, AD 46 (KCNQ5)
• Intellectual developmental disorder, AD 56 (CLTC)
• Intellectual developmental disorder, AD 7 (DYRK1A)
• Intellectual developmental disorder, AR 38 (HERC2)
• Intellectual developmental disorder, AR 74 (APC2)
• Intellectual developmental disorder, XL 1 (IQSEC2)
• Intellectual developmental disorder, XL 29 (ARX)
• Intellectual developmental disorder, XL syndromic, Lubs type (MECP2)
• Intellectual developmental disorder, XL, syndrome, Snijders Blok type (DDX3X)
• Intellectual developmental disorder, XL, syndromic 13 (MECP2)
• Intellectual developmental disorder, XL, syndromic, Bain type (HNRNPH2)
• Intellectual developmental disorder, XL, syndromic, Cabezas type (CUL4B)
• Intellectual developmental disorder, behav. abn., craniofac. dysmorph. with/-out seizures (PHF21A)
• Intellectual developmental disorder, dysmorphic facies, seizures, distal limb anomalies (OTUD6B)
• Intellectual developmental disorder, hypotonia + behavioral abnormalities (CDK8)
• Intellectual developmental disorder, macrocephaly, seizures, speech delay (PAHK1)
• Intellectual developmental disorder, seizures + language delay (SETD1B)
• Intellectual developmental disorder, with/-out nystagmus (CASK)
• Intellectual disability-hypotonic facies syndrome, XL (ATRX)
• Jaberi-Elahi syndrome (GTPBP2)
• Joubert syndrome 9 (CC2D2A)
• KBG syndrome (ANKRD11)
• Kleefstra syndrome 1 (EHMT1)
• Krabbe disease (GALC)
• LEOPARD syndrome 3 (BRAF)
• Language delay + ADHD/cognitive impairment with/-out cardiac arrhythmia (GNB5)
• Leukodystrophy, hypomyelinating, 18 (DEGS1)
• Leukodystrophy, hypomyelinating, 3 (AIMP1)
• Leukoencephalopathy, progressive, infantile-onset, with/-out deafness (KARS1)
• Li-Ghorgani-Weisz-Hubshman syndrome (KAT8)
• Liang-Wang syndrome (KCNMA1)
• Lipodystrophy, congenital generalized, type 2 (BSCL2)
• Lissencephaly 10 (CEP85L)
• Lissencephaly 9 with complex brainstem malformation (MACF1)
• Lissencephaly, XL (DCX)
• Lissencephaly, XL 2 (ARX)
• Lujan-Fryns syndrome (MED12)
• MEHMO [M retard., Epilepsy, Hypogonadism/hypogenitalism, Microcephaly, Obesity] syndrome (EIF2S3)
• Mandibulofacial dysostosis, Guion-Almeida type (EFTUD2)
• Maple syrup urine disease, type II (DBT)
• Maple syrup urine disease, type Ia (BCKDHA)
• Maple syrup urine disease, type Ib (BCKDHB)
• Meckel syndrome 6 (CC2D2A)
• Mega-corpus-callosum syndrome, cerebellar hypoplasia, cortical malformations (MAST1)
• Megalencephalic leukoencephalopathy with subcortical cysts 2A (HEPACAM)
• Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, +/- MR (HEPACAM)
• Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (AKT3)
• Menkes disease (ATP7A)
• Mental retardation, AR 41 (KPTN)
• Methylmalonic aciduria + homocysteinemia, cblX type (HCFC1)
• Microangiopathy + leukoencephalopathy, pontine, AD (COL4A1)
• Microcephaly, postnatal progressive, with seizures + brain atrophy (MED17)
• Microcephaly, progressive, seizures, cerebral + cerebellar atrophy (QARS)
• Migraine, familial basilar (ATP1A2)
• Migraine, familial hemiplegic, 2 (ATP1A2)
• Mitochondrial DNA depletion syndrome 13, encephalomyopathic type (FBXL4)
• Mitochondrial complex III deficiency, nuclear type 1 (BCS1L)
• Mucopolysaccharidosis type IVB, Morquio (GLB1)
• Multiple congenital anomalies-hypotonia-seizures syndrome 1 (PIGN)
• Multiple congenital anomalies-hypotonia-seizures syndrome 2 (PIGA)
• Multiple congenital anomalies-hypotonia-seizures syndrome 3 (PIGT)
• Multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia (BOLA3)
• Multiple mitochondrial dysfunctions syndrome 3 (IBA57)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 4 (FKTN)
• Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 4 (FKTN)
• Myasthenic syndrome, congenital, 13, with tubular aggregates (DPAGT1)
• NESCAV syndrome (KIF1A)
• Neurodegeneration due to cerebral folate transport deficiency (FOLR1)
• Neurodevelopmental disorder with cerebellar atrophy with/-out seizures (BRAT1)
• Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia (MADD)
• Neurodevelopmental disorder with dysmorphic facies, sleep disturbance + brain abnormalities (KAT5)
• Neurodevelopmental disorder with hypotonia, microcephaly + seizures (ADARB1)
• Neurodevelopmental disorder with nonspecific brain abnormalities with/-out seizures (DLL1)
• Neurodevelopmental disorder with progressive spasticity + brain white matter abnormalities (HPDL)
• Neurodevelopmental disorder with/-out early-onset generalized epilepsy (NBEA)
• Neurodevelopmental disorder with/-out seizures + gait abnormalities (GRIA4)
• Neurodevelopmental disorder, absent language + variable seizures (WASF1)
• Neurodevelopmental disorder, brain anomalies, seizures + scoliosis (PIGU)
• Neurodevelopmental disorder, epilepsy, cataracts, feeding diff. + delayed brain myelinat. (NACC1)
• Neurodevelopmental disorder, hypotonia, autistic features with/-out hyperkinetic movements (VAMP2)
• Neurodevelopmental disorder, hypotonia, impaired expressive language with/-out seizures (DEAF1)
• Neurodevelopmental disorder, hypotonia, seizures + absent language (HECW2)
• Neurodevelopmental disorder, impaired speech, hyperkinetic movements (ZNF142)
• Neurodevelopmental disorder, language delay with/-out structural brain abnormalities (PPP2CA)
• Neurodevelopmental disorder, microcephaly, epilepsy + brain atrophy (TRAPPC6B)
• Neurodevelopmental disorder, microcephaly, seizures + cortical atrophy (VARS1)
• Neurodevelopmental disorder, mitoch., abn. movements, lactic acidosis, with/-out seizures (WARS2)
• Neurodevelopmental disorder, progressive microcephaly, spasticity + brain anomalies (PLAA)
• Neurodevelopmental disorder, regression, abnormal movements, speechless, seizures (IRF2BPL)
• Neurodevelopmental disorder, seizures, speech + walking impairment (DHPS)
• Neurodevelopmental disorder, severe motor impairment + absent language (DHX30)
• Neurodevelopmental disorder, spastic quadriplegia, brain abnormalities with/-out seizures (WDR45B)
• Neurooculocardiogenitourinary syndrome (WDR37)
• Noonan syndrome 3 (KRAS)
• Noonan syndrome 7 (BRAF)
• O'Donnell-Luria-Rodan syndrome (KMT2E)
• Occipital horn syndrome (ATP7A)
• Ohdo syndrome, XL (MED12)
• Opitz-Kaveggia syndrome (MED12)
• Optic atrophy 10 with/-out ataxia, mental retardation + seizures (RTN4IP1)
• Paroxysmal nonkinesigenic dyskinesia, 3, with/-out generalized epilepsy (KCNMA1)
• Partington syndrome (ARX)
• Periventricular heterotopia with microcephaly (ARFGEF2)
• Poirier-Bienvenu neurodevelopmental syndrome (CSNK2B)
• Polymicrogyria, bilateral frontoparietal (ADGRG1)
• Polymicrogyria, bilateral perisylvian (ADGRG1)
• Pontocerebellar hypoplasia, type 1B (EXOSC3)
• Pontocerebellar hypoplasia, type 9 (AMPD2)
• Primary aldosteronism, seizures + neurologic abnormalities (CACNA1D)
• Proud syndrome (ARX)
• Raynaud-Claes syndrome (CLCN4)
• Rett syndrome (MECP2)
• Rett syndrome, atypical (MECP2)
• Rett syndrome, congenital variant (FOXG1)
• Rett syndrome, preserved speech variant (MECP2)
• Rigidity and multifocal seizure syndrome, lethal neonatal (BRAT1)
• SESAME syndrome (KCNJ10)
• Sandhoff disease, infantile, juvenile + adult forms (HEXB)
• Seizures, benign neonatal, 2 (KCNQ3)
• Seizures, cortical blindness, microcephaly syndrome (DIAPH1)
• Short stature, brachydactyly, intellectual developmental disability + seizures (PRMT7)
• Silver spastic paraplegia syndrome (BSCL2)
• Singleton-Merten syndrome 1 (IFIH1)
• Spastic paraplegia + psychomotor retardation with/-out seizures (HACE1)
• Spastic paraplegia 30, AD (KIF1A)
• Spastic paraplegia 30, AR (KIF1A)
• Spastic paraplegia 35, AR (FA2H)
• Spastic paraplegia 63 (AMPD2)
• Spastic paraplegia 74, AR (IBA57)
• Spastic paraplegia 77, AR (FARS2)
• Spastic paraplegia 82, AR (PCYT2)
• Spastic paraplegia 83, AR (HPDL)
• Spinal muscular atrophy with progressive myoclonic epilepsy (ASAH1)
• Spinal muscular atrophy, distal, XL 3 (ATP7A)
• Spinal muscular atrophy, lower extremity-predominant 1, AD (DYNC1H1)
• Subcortical laminal heterotopia, XL (DCX)
• Succinic semialdehyde dehydrogenase deficiency (ALDH5A1)
• Tay-Sachs disease (HEXA)
• Temtamy syndrome (C12orf57)
• Vici syndrome (EPG5)
• Vulto-van Silfout-de Vries syndrome (DEAF1)
• Wrinkly skin syndrome (ATP6V0A2)