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Neurology

Epilepsy Genetics

  • This page is intended as a quick reference for genes and copy number variants associated with various electroclinical epilepsy syndromes. It is not a comprehensive listing, nor is it a recommendation for mutation testing in any given circumstance. Many of the listed genes have been implicated in only a few families or individuals. Some have variants whose role in individuals is uncertain and can be found in unaffected people (see Klassen et al).

    More information about gene function and clinical genetics can be found at OMIM and GeneReviews. Hyperlinks to genes in the table search OMIM for that gene. Other links in the table are to syndrome descriptions or other online resources for the condition.

    Please direct suggestions for additions or modifications to the list or the page to Dr Jeremy Freeman.

     

    Electroclinical syndrome Gene
    or CNV    		 Associated features
    (may not be present)    		 Inherit Mutation
    frequency
    Benign familial neonatal epilepsy KCNQ2 Myokymia (one family) AD 80%
      KCNQ3     5%
      inv(5)(p15q11)     1 family
    Benign familial neonatal-infantile epilepsy SCN2A Earlier onset than BFIE, resolves by 12 months AD ? 100%
    Benign familial infantile epilepsy PRRT2 Allelic with familial PKD/C AD 83%
      ATP1A2 Allelic with familial hemiplegic migraine   1 family
      KCNQ2     1 family
    Early myoclonic encephalopathy (EME) AMT Glycine encephalopathy AR  
    AND GLDC Glycine encephalopathy AR  
    Early infantile epileptic encephalopathy with suppression-bursts (EIEE) GCSH Glycine encephalopathy AR  
    AND PNPO PLP-dependent AR  
    Infantile epileptic encephalopathy NOS ALDH7A1 B6-dependent, folinic acid responsive AR  
    (Infantile epilepsies progressing to West syndrome and Lennox-Gastaut syndrome included) BTD Biotinidase deficiency, skin changes (~10% only) AR  
      MTHFR Elevated homocysteine, PV WM hyperintensities AR  
      ATP7A low Cu2+, kinky hair, low CSF catecholamines X  
      SUOX Sulfite oxidase deficiency AR  
      MOCS1/2 Molybdenum cofactor deficiency AR  
      GPHN Molybdenum cofactor deficiency AR  
      PCCA/B Propionic acidaemia, myoclonus, photosensitivity AR  
      GLYCTK D-glyceric acidaemia, glycine encephalopathy AR  
      ARX Allelic with XLAG, dyskinesia, BG hyperintensities X 7%
      CDKL5 Atypical Rett syndrome, normal early interictal EEG XD  
      SLC25A22 Cerebellar hypoplasia, CC malformation AR  
      STXBP1   AD 6%
      SPTAN1 Cerebral atrophy, hypomyelination AD  
      KCNQ2 Early (resolving) thalamic/BG hyperintensities AD  
      ARHGEF9 Hyperpekplexia and epilepsy X  
      PCDH19 Family history of epilepsy/MR limited to females X-L2F  
      PNKP Congenital microcephaly, simplified gyri AR  
      SCN2A Late episodic ataxia and myoclonus AD  
      PLCB1 Allelic with MMPSI AR  
      SCN8A   AD  
      SLC2A1 GLUT1-DS, FHx of paroxysmal exertional dystonia AD  
      MECP2 Atypical Rett syndrome XD  
      FOXG1 Atypical Rett syndrome AD  
    Migrating focal seizures of infancy (MMPSI) KCNT1 Delayed myelination, cortical atrophy, thin CC AD 50%
      SCN1A   AD 13%
      PLCB1   AR 2 cases
      TBC1D24   AR 1 family
    West syndrome TSC1/2 Tuberous sclerosis AD 20%
    (where onset of spasms without other prior seizures is reported) ARX Allelic with XLAG, DD prior to ES, spasticity X  
      CDKL5 Rare without prior seizures, DD prior to ES XD  
      STXBP1 Rare without prior seizures AD  
      ST3GAL3 No seizures prior to ES in all reported cases AR  
      ADSL Urine SAICAR elevated, Angelman-like AR  
      trisomy 21 Down syndrome    
      del 7q11.23 Williams-Beuren syndrome    
      dup FOXG1 Atypical Rett syndrome    
      dup 16p11.2      
      ?Xp22 Aicardi syndrome ?XD  
    Benign myoclonic epilepsy of infancy (BMEI) TBC1D24 Familial infantile myoclonic epilepsy (FIME) AR  
    Dravet syndrome (SMEI) SCN1A   AD 61-87%
    (SMEB included) SCN2A      
      GABRG2      
      SCN8A      
      PCDH19 Similar to Dravet syndrome (in some cases) X-L2F  
    Febrile seizures (FS+ included) SCN1A   AD  
      SCN2A      
      SCN1B      
      GABRD      
      GABRG2      
      PCDH19 Family history of epilepsy/MR limited to females X-L2F  
    Epilepsy with myoclonic-astatic seizures (MAE) SLC2A1 GLUT1-DS, PED, ataxia AD 5%
      SCN1A   AD  
    Benign epilepsy with centrotemporal spikes (BECTS/BFEC) - No concordance in MZ and DZ twins    
    Atypical BFEC (CSWS/ESES and Landau-Kleffner syndrome included) SRPX2 Rolandic epilepsy, speech dyspraxia (+/- PMG) X  
    Childhood absence epilepsy (CAE) SLC2A1 10% of early onset cases (less than 4 years) AD  
      GABRG2   AD  
      GABRA1   AD  
      CACNA1H Han Chinese, contributory in polygenic causaton    
    Juvenile absence epilepsy (JAE) EFHC1 Familial GGE AD  
    Juvenile myoclonic epilepsy (JME) SLC2A1 Familial GGE, paroxysmal exertional dystonia AD  
      EFHC1 Familial GGE AD 3-9%
      GABRA1 Familial JME AD  
      CACNB4 GGE with episodic ataxia, acetazolamide responsive AD  
      GABRD   AD  
      CLCN2 Implicated in other GGE but significance unknown AD  
    Genetic generalised epilepsy (GGE) SLC2A1 Familial GGE, paroxysmal exertional dystonia AD 1%
    (Phenotypes include CAE, JAE, JME, MAE, FS+ and GGE NOS) CACNB4 GGE with episodic ataxia, acetazolamide responsive AD  
      CACNA1A GGE, episodic ataxia, familial hemiplegic migraine AD  
      CACNA1H variants contributory in up to 8% of patients    
      del 15q13.3     1%
      del 16p13.11     1%
      del 15q11.2     1%
    Autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE) CHRNA4   AD  
      CHRNA2   AD  
      CHRNB2   AD  
      KCNT1 More severe with psychiatric features and ID AD  
    Autosomal-dominant epilepsy with auditory features (ADEAF) LGI1   AD 50%
    Familial focal epilepsy with variable foci (FFEVF) DEPDC5 Includes some familial TLE/FLE AD 12-37%
    Epilepsy and autism/ID BCKDK Reduced plasma branched chain amino acids AR  
      SYN1   X  
      GRIN2A Epilepsy and mental retardation AR