Differential Diagnosis
Epileptic encephalopathies presenting with seizures as prominent/unique symptom
Vitamin or enzymatic cofactor dependency- Pyridoxine dependent epilepsy
- Folinic acid responsive epilepsy
- Pyridoxal-5′-phosphate responsive epilepsy
Channellopathies
- Dravet and Dravet-like syndrome
Unknown/multiple etiology
- Ohtahara syndrome (EIEE)
- Early myoclonic encaphalopathy (EME)
Single enzyme or protein dysfunction
- Syntaxin binding Protein 1 (STXBP1) deficiency
- Glutamate mitochondrial transporters deficiencies (SLC25A22 and SLC25A18)
- Phospholipase C beta-1 deficiency
- MAGI2 related epileptic encephalopathy
- Protocadherin 19 related epileptic encephalopathy
Disorders of amino acids metabolism
- Hyperprolinemia type II
- Neurotransmitters disorders
- GABA transaminase deficiency
Epileptic encephalopathies presenting with seizures associated in a syndromic phenotype associated with Suggestive somatic characteristics (i.e. dysmorphic features and/or alterations of head circumference)
Chromosomopathies
- 1p36 monosomy
- Wolf-Hirschhorn syndrome
- 18q- syndrome
- Angelman syndrome
- Ring chromosome 20 syndrome
- Down syndrome
Single enzyme or protein dysfunction
- Cyclin-dependent kinase-like 5 (CDKL5) deficiency
- Rett Syndrome (MeCP2, CDKL5 or FOXG1-related)
Cerebral malformations associated disorders
- Focal cortical dysplasia (TSC1 and TSC2)
- Polymicrogyria (SRPX2, KIAA1279, GPR56, PAX6, TBR2, COL18A1,
- RAB3GAP1, 22q11., FLN1A, ARFGEF2, LRP)
- Subcortical band heterotopia (DCX, LIS1, trisomy 9p)
- Periventricular nodular heterotopia (unbalanced translocation,t[1; 6][p12; p12.2)]
- Lissencephaly (LIS1, DCX, microdeletion in 17p including LIS1 and
- YwaE, ARX, TUBA1A, RELN)
- Schizencephaly (EMX2 involved in sporadic cases)
- Early infantile epileptic encephalopathy type I (ARX-related EIEE1)
- Miller-Dieker syndrome
- Smith-Lemli–Opitz syndrome
Disorders of amino acids metabolism
- Phenylketonuria and hyperphenylalaninemias
- Vitamin or enzymatic cofactor dependency
- Sulfite oxidase deficiency
- Molybdenum cofactor deficiency
- Menkes disease
- Purine and pyrimidine metabolism disorders
- Adenilosuccinate lyase deficiency
- Dihydropyriminidase and Dihydropyrimidine dehydrogenase deficiency
Epileptic encephalopathies presenting with Seizures associated with Movement disorders
Energetic failure
- GLUT1 deficiency syndrome
- Creatine deficiency syndromes (AGAT, GAMT and X-linked creatine transporter deficiency)
- Cerebral malformations associated disorders
- EIEE1 (ARX-related epileptic encephalopathy)
Neurotransmitters disorders
- 4-hydroxybutyric aciduria (SSADH)