TABLE 2.
Clinical characteristics of 17 cases of genetic DEE/EE with ESES.
| Cases | Case 1 | Case 2 | Case 3 | Case 4 | Case 5 | Case 6 |
| Gender, age | M, 2 y 4 m | M, 8 y 9 m | F, 1 y 11 m | F, 2 y 1 m | M, 4 y 10 m | M, 4 y 4 m |
| Gene, mutations | KCNQ2 c.736G>C (p.Ala246Pro) de novo | KCNQ2 c.998G>A (p.Arg333Gln) paternal | KCNQ2 c.920T>C (p.Leu307Pro) de novo | KCNQ2 c.832A>T (p.Ile278Phe) de novo | KCNQ2 c.740C>T (p.Ser247Leu) de novo | KCNQ2 c.952C>G (p.Leu318Val) de novo |
| Age at epilepsy onset/seizure type | 1 d/focal seizure | 2 d/GTCS | 2 d/tonic seizure | 3 d/tonic seizure | 2 d/focal seizure | 5 m/spasm |
| Other seizure types | Spasm, AA ± SE | Clonic seizure, focal seizure during sleep | Spasm, focal seizure, FS+SE | Focal seizure | FS, spasm | MC |
| Seizure outcome | Seizure controlled 2 m–1 y 7 m. breakthrough AA ± SE at age 1 y 7 m | Seizure controlled since 8 y 1 m | Uncontrolled | Uncontrolled | Seizure controlled 6 m–4 y 10 m. breakthrough spasms at age 4 y 10 m | Seizure free since 10 m (controlled by adrenocorticotrophic hormone) |
| EEG at onset | Hypsarrhythmia | Multifocal SW and Sh-W | Burst suppression | Burst suppression | Multifocal SW and Sh-W | Hypsarrhythmia |
| EEG in the evolution (age at ESES onset) | GSW with Ar or Pr predominance SWI 85–100% (1 y 7 m) | Sp and SW in Rolandic region SWI 85–90% (3 y 5 m–7 y 1 m) | SW and polySp in Pr regions SWI 75–85% (1 y 11 m) | Multifocal SW and Sh-W with Rolandic predominance SWI 95% (1 y 1 m) | Sp and Sh-W in Rolandic region SWI > 85% (1 y 10 m–4 y 10 m) | EEG normalized 1 y–1 y 10 m Sp and Sh-W in Rolandic region SWI>50% (2 y 3 m) |
| Current AEDs | TPM, VGB, LTG | VPA, CZP, LTG | LEV, VPA | VPA, TPM | LEV, TPM, OXC | – |
| Development before seizure onset | Delayed from birth | Delayed from birth | Delayed from birth | Delayed from birth | Delayed from birth | Delayed from birth |
| Neurological features after seizure onset | Psychom.dev. delay Psychom.dev. improved after focal seizures and spasms controlled | Psychom.dev. delay Severe language delay Psychom.dev. improved after seizure free | Psychom.dev. delay Poor visual contact, head deviation to one side | Psychom.dev. delay Poor visual contact, head deviation to one side | Psychom.dev. delay Psychom.dev. improved after seizure free 6 m–4 y 10 m | Psychom.dev. regression Language delay, impairment of fine motor skills |
| Imaging | Cerebral atrophy | Delayed myelination | Diffuse cortical dysplasia | Diffuse cortical dysplasia | Agenesis of the corpus callosum | Agenesis of the corpus callosum |
| Additional features | – | Family history of epilepsy | – | Hemolysis neonatorum | – | Test tube baby (twins) Pathologic jaundice |
| EEG, electroencephalogram; AEDs, anti-epileptic drugs; M, male; y, years; m, months; d, days; AA, atypical absence; SE, status epilepticus; GSW, generalized spike and waves; Ar, anterior; Pr, posterior; ESES, electrical status epilepticus during sleep; SWI, spike-wave index; TPM, topiramate; VGB, vigabatrin; LTG, lamotrigine; Psychom.dev., psychomotor developmental; GTCS, generalized tonic–clonic seizure; SW, spike-waves; Sh-W, sharp-waves; Sp, spikes; VPA, valproic acid; CZP, clonazepam; F, female; FS, febrile seizure; polySp, polyspikes; LEV, levetiracetam; MC, myoclonus. | ||||||
| Cases | Case 7 | Case 8 | Case 9 | Case 10 | Case 11 | |
| Gender, age | F, 8 y 11 m | M, 7 y 7 m | M, 2 y 11 m | M, 4 y 4 m | F, 2 y 8 m | |
| Gene, mutations | KCNA2 c.1214C>T (p.Pro405Leu) paternal | KCNA2 c.1214C>T (p.Pro405Leu) de novo | KCNA2 c.1214C>T (p.Pro405Leu) de novo | KCNA2 c.1214C>T (p.Pro405Leu) de novo | KCNA2 c.1214C>T (p.Pro405Leu) de novo | |
| Age at epilepsy onset/seizure type | 11 m/Febrile tonic–clonic seizure | 6 m/focal seizure | 8 m/focal seizure | 10 m/MC | 5 m/afebrile tonic–clonic seizure | |
| Other seizure types | Focal seizures during sleep, SE, ENM | ENM, FS | AA ± atonic, febrile SE | focal seizure during sleep | MC, SE, FS, focal seizures during sleep | |
| Seizure outcome | Seizure controlled since 6 y 8 m | Focal seizures controlled since 2 y 8 m, ENM controlled since 5 y 8 m | Uncontrolled | Uncontrolled | Uncontrolled | |
| EEG at onset | N | N | GSW with Pr predominance | GSW with Pr predominance | GSW with Pr predominance | |
| EEG in the evolution (age at ESES onset) | Multifocal SW and Sh-W with Rolandic predominance SWI 60–85% (3 y 9 m) | Sp and Sh-W in Rolandic region SWI 60–85% (5 y 4 m) | Sp and Sh-W in Rolandic region, GSW SWI > 85% (2 y 5 m) | Sp and Sh-W in Rolandic region ± GSW SWI 60–85% (2 y 11 m) | Sp and Sh-W in Rolandic region SWI 70% (2 y 7 m) | |
| Current AEDs | VPA, CZP | VPA, LEV, CLB | VPA, CZP, LEV | VPA, LEV | VPA, LEV | |
| Development before seizure onset | N | N | N | N | N | |
| Neurological features after seizure onset | Psychom.dev. regression Severe language delay, impairment of fine motor skills, Psychom.dev. improved after seizure free | Psychom.dev. regression Severe language delay, impairment of fine motor skills, tremor, Psychom.dev. improved after seizure free | Psychom.dev. regression Language delay | Psychom.dev. regression Language delay | Psychom.dev. regression Language delay | |
| Imaging | N | N | N | N | N | |
| Additional features | Family history of epilepsy | Neonatal asphyxia | Family history of epilepsy | – | – | |
| EEG, electroencephalogram; AEDs, anti-epileptic drugs; F, female; y, years; m, months; SE, status epilepticus; ENM, epileptic negative myoclonus; N, normal; SW, spike-waves; Sh-W, sharp-waves; ESES, electrical status epilepticus during sleep; SWI, spike-wave index; VPA, valproic acid; CZP, clonazepam; Psychom.dev., psychomotor developmental; M, male; FS, febrile seizures; Sp, spikes; LEV, levetiracetam; CLB, clobazam; AA, atypical absence; GSW, generalized spike and waves; Pr, posterior; MC, myoclonic seizures. | ||||||
| Cases | Case 12 | Case 13 | Case 14 | Case 15 | Case 16 | Case 17 |
| Gender, age | F, 5 y 6 m | M, 4 y 6 m | F, 6 y 5 m | M, 8 y | M, 7 y 10 m | M, 3 y 6 m |
| Gene, mutations | GRIN2A c.1034delG (p.Gly345Alafs*19) de novo | GRIN2A c.2107C>T (p.Gln703*) de novo | GRIN2A c.1592C>T (p.Thr531Met) de novo | SLC9A6 c.1178_1180del (p.394del) de novo | HIVEP2 c.5935C>T (p.Arg1979*) de novo | RARS2 c.[991A>G; 1718C>T] (p.[Thr573Ile; Ile331Val]) de novo |
| Age at epilepsy onset/seizure type | 2 y 4 m/focal seizure during sleep | 3 y 6 m/focal seizure during sleep | 3 y 10 m/focal seizure during sleep ± sGTCS | 1 y 11 m/focal seizure | 4 y 4 m/febrile GTCS | 3 m/MC |
| Other seizure types | AA, MC | – | SE, FS | Febrile GTCS, MC, AA | Focal seizures, AA | Focal seizures, AA |
| Seizure outcome | Seizure controlled since 5 y | Uncontrolled | Seizure controlled since 5 y 2 m | Uncontrolled | Uncontrolled | Uncontrolled |
| EEG at onset | BG slowing, Multifocal Sp and Sh-W | Multifocal Sp with Rolandic predominance | Multifocal Sp and Sh-W with Pr predominance | Sp in Fr region with right predominance | Sh-W in Fz | GSW |
| EEG in the evolution (age at ESES onset) | BG slowing, Sp, and Sh-W in Rolandic region SWI 85–100% (4 y 6 m–5 y 6 m) | Sp and Sh-W in Rolandic region SWI 50–60% (4 y 6 m) | Sp and Sh-W in Rolandic region SWI 70% (5 y 8 m) | Sp and Sh-W in Ar region SWI 60–95% (3 y 3 m) | Multifocal Sp and Sh-W with Rolandic predominance SWI 80–100% (5 y 6 m) | Sp and Sh-W in Rolandic region SWI 85% (3 y 6 m) |
| Current AEDs | VPA, LEV, CZP | VPA, LEV | VPA, LEV, CZP | VPA, LEV | VPA, CZP, LEV | TPM, PB |
| Development before seizure onset | N | Language delay, impairment of motor skills | Language and reaction delay | Delayed from birth | Considerable global delay at 2 years old | Delayed from birth |
| Neurological features after seizure onset | Psychom.dev. regression Severe language and reaction delay, self-care disability | Psychom.dev. regression Severe language delay | Psychom.dev. regression Severe language delay | Psychom.dev. regression Severe language delay, independent but ataxic walking aggressiveness, hyperactivity | Psychom.dev. regression Severe language delay, impairment of gross and fine motor coordination | Psychom.dev. regression Impairment of gross and fine motor skills, language delay |
| Imaging | N | N | N | N | N | Cerebral atrophy; progressive white matter depletion |
| Additional features | – | Premature birth, neonatal asphyxia | – | Prevention of miscarriage | Broad forehead, hypotonia, malnutrition | Hypotonia, progressive microcephaly |
EEG, electroencephalogram; AEDs, anti-epileptic drugs; F, female; y, years; m, months; AA, atypical absence; MC, myoclonic seizures; BG, background; Sp, spikes; Sh-W, sharp-waves; ESES, electrical status epilepticus during sleep; SWI, spike-wave index; VPA, valproic acid; LEV, levetiracetam; CZP, clonazepam; N, normal; Psychom.dev., psychomotor developmental; M, male; sGTCS, secondary generalized tonic–clonic seizure; SE, status epilepticus; FS, febrile seizures; Pr, posterior; GTCS, generalized tonic–clonic seizure; Ar, anterior; GSW, generalized spike and waves; TPM, topiramate; PB, phenobarbitone. The symbol * is used to indicate a translation termination (stop) codon.