Table 1.
Summary of the genetic and clinical findings of nonlesional epilepsy syndromes
| Epilepsy/syndrome | Gene | Locus | Seizures | ID | Other features | No. of reported mutationsa |
|---|---|---|---|---|---|---|
| SCN1A-related epilepsies | ||||||
| Dravet syndrome | SCN1A; SCN1B; GABRG2, PCDH19 | 2q24; 19q13; 5q31 | Fever related hemiclonic; TC, My; Ab; focal sz | Yes | From mild to severe developmental delay | SCN1A: 853 |
| SCN1B: 2 | ||||||
| GABRG2: 1 | ||||||
| PCDH19: 1 | ||||||
| GEFS+ | SCN1A; SCN1B; GABRG2 | 2q24; 19q13; 5q31 | FS, FS+; focal, afebrile TC | ± | No | SCN1A:58 |
| SCN1B: 5 | ||||||
| GABRG2: 7 | ||||||
| Epilepsy and migraine | SCN1A | 2q24 | Focal sz | No | No | 1 |
| Benign epilepsies in newborns and infants | ||||||
| Neonatal | KCNQ2/KCNQ3 | 20q13; 8q24 | Clusters of focal sz | No | Movement disorders; migraine | KCNQ2: 87 |
| KCNQ3: 6 | ||||||
| Neonatal–infantile | SCN2A | 2q23 | 19 | |||
| Infantile | PRRT2 | 16p12 | 9 | |||
| ICCA | PRRT2 | 16p12 | 12 | |||
| Epileptic encephalopathies | ||||||
| Neonatal EE | KCNQ2 | 20q13 | Clusters of focal sz and SB EEG pattern | Yes | 14 | |
| PCDH19-related phenotype | PCDH19 | Xq22 | Clusters of focal febrile/afebrile sz | 70% | ASD | 32 |
| CDKL5-related phenotype | CDKL5 | Xp22 | Tonic, spasms, TC, My | Yes | ASD, severe DD | 69 |
| Otahara syndrome and West syndrome | ARX | Xp22 | Spasms, tonic, SB EEG pattern | Yes | Severe DD, dystonia | 15 |
| STXBP1 | 9q34 | Spasms, tonic SB EEG pattern | Yes | Severe DD; movement disorders | 14 | |
| MMPSI | KCNT1 | 9q34 | Migrating focal | Yes | Severe developmental delay | 6 |
| CSWS/LKS | GRIN2A | 16p13 | Focal sz | Yes | Acquired aphasia | 27 |
| Familial focal epilepsies | ||||||
| ADNFLE | CHRNA4, CHRNB2; CHRNA2; KCNT1 | 20q13, 1q21, 8p21 | Nocturnal focal sz | Learning disabilities | CHRNA4: 6 | |
| CHRNB2: 6 | ||||||
| CHRNA2: 1 | ||||||
| KCNT1: 4 | ||||||
| ADEAF | LGI1 | 10q24 | Focal sz | No | No | 13 |
| FFEVF | DEPDC5 | 20q11 | Focal sz | No | No | 18 |
| IGEs | ||||||
| Rare AD families | GABRA1 | 5q34 | TC, My | No | No | 2 |
| GABRG2 | 5q31 | Ab, TC | 1 | |||
| CLCN2 | 3q26 | Generalized | 8 | |||
| CACNA1H | 16p13 | 6 | ||||
| GABRD | 1p36 | 1 | ||||
| ME2 | 18q21 | 1 | ||||
| BRD2 | 6p21 | 2b | ||||
| NEDD4 | 15q | 3 | ||||
| Small multiplex families | No | 18q, 2q, 3q, 14q | ||||
Ab absences; AD autosomal dominant; ADEAF autosomal dominant lateral temporal lobe epilepsy; ADNFLE autosomal dominant nocturnal frontal lobe epilepsy; ASD autism spectrum disorders; CDKL5 cyclin-dependent kinase-like 5; CSWS continuous slow waves in slow sleep; DD developmental delay; EE epileptic encephalopathies; EEG electroencephalogram; FFEVF autosomal dominant epilepsy with variable foci; FS febrile sizures; FS+ febrile seizures plus; GEFS+ generalized epilepsy with febrile seizures plus; ICCA incantile convulsions coreoathetosis; ID intellectual disabilities; IGE infantile generalized epilepsy; LKS Landau–Klefner syndrome; MMPSI malignant migrating partial seizures of infancy; My myoclonic; PCDH19 protocadherin 19; SB suppression-burst; sz seizures; TC tonic–clonic
aAccording to Human Gene Mutation Database Professional 2013.4 (http://www.hgmd.cf.ac.uk/ac/index.php), Online Mendelian Inheritance in Man (http://www.omim.org/), and PubMed (www.ncbi.nlm.nih.gov/pubmed)
bSingle nucleotide polymorphisms strongly associated with the disease