TABLE 3.
Patients with KCNH1 variant with epilepsy
| References | Age/sex | Variants (NM_172362) | Inheritance | Onset of seizures | Epilepsy/seizure types | TBS/ZLS | Intellectual disability (ID)/developmental delay (DD) | Effective ASM and outcomes of epilepsy |
|---|---|---|---|---|---|---|---|---|
| De novo | ||||||||
| vonWrede 37 | 6 yrs 4 mons/M | c.596A>G; p.Lys199Arg | De novo | 2.5 yrs | FS, DEE, GTCS, myoclonic, SE | No | Psychomotor development was severely impaired | Cortisone, perampanel, and topiramate were effective |
| Simons 33 | 6 yrs/F | c.651G>C; p.Lys217Asn | De novo | 6 yrs | Generalized tonic‐clonic seizure | TBS | Mild psychomotor development delay | NA |
| Rochtus 29 | 11 yrs/M | c.796G>A; p.Val266Met | De novo | 2.5 yrs | Myoclonic, GTCS, absence, and drop seizures | No | Mild delay | NA, but she got seizure‐free and off medication |
| Kortüm 25 | 21 yrs/M | c.1055C>A; p.Ser352Tyr | De novo | Childhood | Frequent seizures, SE | ZLS | Profound ID/DD | NA |
| Gripp 24 | 2.9 yrs/F | c.1060A>G; p.Lys354Glu | De novo | 4 weeks | NA | TBS | Motor and speech delay; skills at 4 m level at age 2.8 | NA |
| Present study | 1 yrs 10 mons/M | c.1069C>T; p.Arg357Trp | De novo | 8 mons | Fever sensitivity, GTCS, focal, SE. | No | Mild delay | Valproic acid, seizure‐free |
| Fukai 23 | 8 yrs/M | c.1070G>A; p.Arg357Gln | De novo | 6 mons | generalized tonic‐clonic | TBS | Severe ID and DD | Epilepsy was controlled by valproic acid and zonisamide |
| Bramswig 5 | 14 yrs/F | c.1070G>A; p.Arg357Gln | De novo | 1.5 yrs | Focal epilepsy with secondary generalization | TBS | Severe ID and DD | NA |
| Bramswig 5 | 4 yrs 4 mons/F | c.1070G>A; p.Arg357Gln | De novo | 2 yrs 9mons | Frequent temporal epilepsy, SE | TBS | Severe ID and DD, ASD | NA |
| Fukai 23 | 6 yrs/M | c.1070G>A; p.Arg357Gln | De novo | 1 mon | Focal seizures | No | Severe ID and DD | His seizures were controlled by frisium, trileptin, and risperdal |
| Gripp 24 | 9.7 yrs/F | c.1070G>A; p.Arg357Gln | De novo | 2.75 yrs | Focal, GTCS, and absences | TBS | Severe DD/ID | NA |
| Fukai 23 | 7 yrs/M | c.1070G>C; p.Arg357Pro | De novo | 4 mons | Generalized tonic‐clonic | No | Severe ID and DD | Carbamazepine, and clobazam, relative effectiveness |
| Kortüm 25 | 19 yrs/F | c.1123G>A; p.Gly375Arg | De novo | Adolescence | NA | ZLS | Severe/profound ID | NA |
| Kortüm 25 | 7 yrs/M | c.1135C>G; p.Leu379Val | De novo | 8 mons | Focal clonic secondary generalized seizures, SE | ZLS | Severe intellectual and motor disability | Generalized drug‐resistant seizures |
| Kortüm 25 | 21 yrs/M | c.1147G>C; p.Val383Leu | De novo | Childhood | Frequent seizures, | ZLS | Profound DD/ID | NA |
| Bramswig 5 | 14 yrs/F | c.1465C>T; p.Leu489Phe | De novo | 9 mons | GTCS, absences | TBS | Severe ID and DD | Seizures were responding well to lamotrigine and ethymal |
| Rochtus 29 | 3 yrs/M | c.1474G>A; p.Ala492Thr | De novo | Neonatal | DEE | No | Severe ID and DD | NA |
| Froukh 22 | 5 mons/M | c.1474G>A; p.Ala492Thr | De novo | NA | DEE | TBS | Mild DD/ID | NA |
| Mastrangelo 28 | NA | c.1475C>A; p.Ala492As | De novo | Infancy | GTCS | No | Severe ID/DD | Responsive to levetiracetam |
| Simons 33 | 3 yrs 7 mons/M | c.1480A>G; p.Ile494Val | De novo | 3 yrs | FS, GTCS | TBS | Moderate ID/DD | NA |
| Simons 33 | 4 yrs/M | c.1480A>G; p.Ile494Val | De novo | 4 yrs | NA | TBS | Severe ID/DD | NA |
| Simons 33 | 9 yrs/F | c.1480A>G; p.Ile494Val | De novo | 8 yrs | NA | TBS | Severe ID/DD | NA |
| Kortüm 25 | 12 yrs 8 mons/F | c.1480A>G; p.Ile494Val | De novo | 10 yrs 6 mons | Generalized tonic‐clonic seizures | TBS | Severe DD/ID, autism | NA |
| Kortüm 25 | 4 yrs 6 mons/F | c.1480A>G, p.Ile494Val | De novo | Neonatal | Focal motor seizure, SE | TBS | Severe DD/ID | Seizures were responsive to phenytoin, valproic acid |
| Kortüm 25 | 12 yrs/F | c.1486G>A; p.Gly496Arg | De novo | 6 mons | Focal epilepsy | TBS | Moderate DD/ID | Controlled by tegretol |
| Mastrangelo 28 | 15 yrs/F | c.1486G>A; p.Gly496Arg | De novo | Infancy | Tonic, tonic‐clonic, 2 SE | No | Severe ID | Responsive to lamotrigine, carbamazepine and clobazam |
| Mastrangelo 28 | 9 yrs/F | c.1486G>A; p.Gly496Arg | De novo | Infancy | Focal clonic, generalized tonic‐clonic, myoclonic | No | Mild/moderate ID/DD | Responsive to carbamazepine |
| Mastrangelo 28 | 1.7 yrs/F | c.1486G>A; p.Gly496Arg | De novo | Infancy | Generalized tonic‐clonic, focal clonic, myoclonic | No | Mild ID | Responsive to levetiracetam |
| Fukai 23 | 3 yrs/M | c.1487G>A; p.Gly496Glu | De novo | Neonatal | Generalized convulsions | No | Severe DD and ID | Valproate, clobazam, and levetiracetam were effective |
| Inherited or mosaic | ||||||||
| Present study | 32 yrs/F | c.338T>C; p.Ile113Thr | Parents not tested | Childhood | GTCS | No | No | Medicine was not given, seizure‐free |
| Present study | 4 yrs/M | c.338T>C; p.Ile113Thr | Maternal | 1.5 yrs | GTCS, super SE | No | No | Medication was not given, dead due to SE |
| Simons 33 | NA/F a | c. 1465C>T; p.Leu489Phe | Mosaic (blood 13.6%) | NA | NA | No | No | NA |
| Simons 33 | 14 yrs/F b | c. 1465C>T; p.Leu489Phe | Maternal? | 4 yrs | NA | TBS | Mild/moderate DD/ID | Controlled by topiramate and carbamazepine |
| Simons 33 | NA/F c | c.1508A>G; p.Gln503Arg | Mosaic (blood 4.7%; saliva 4.5%; fibroblast 3.4%) | Childhood | Generalized seizure | No | No | Epilepsy was well controlled with carbamazepine. |
| Simons 33 | 4 yrs/M d | c.1508A>G; p.Gln503Arg | Maternal? | 2 yrs | Generalized seizure | TBS | Mild ID/DD | Well controlled on phenytoin |
| vonWrede 37 | 36 yrs/F | c.1603C>T; p.Arg535* | Paternal | 2 yrs | GTCS, atonic, focal seizures | No | Mild/moderate ID/DD | Controlled by sultiame, phenytoin, and clonazepam |
| Rochtus 29 | 6 yrs/M | c.1717C>T; p.Arg573Cys | Paternal | 2 mons | Focal seizures | No | Global developmental delay | NA |
| vonWrede 37 | 40 yrs/F | c.2138T>A; p.Val713Glu | Maternal | 13 yrs | Absence, tonic, GTCS) | No | No | Drug‐resistant, cannabidiol was partial effective |
| vonWrede 37 | 40 yrs/M | c.2138T>A; p.Val713Glu | Mosaic (brain tissue) | 5 yrs | Multiple seizures, FCD IIb | No | No | Drug‐resistant epilepsy |
| Unknown origin | ||||||||
| Gripp 24 | 34 yrs/F | c.1486G>A; p.Gly496Arg | Father not tested | Neonatal | GTCS, several times SE | ZLS | Mild DD, moderate ID | NA |
| Gripp 24 | 39 yrs/F | c.1487G>A; p.Gly496Glu | Parents not tested | Prenatal | Myoclonic jerks, mixed seizure type | TBS | Severe DD and ID | NA, improved but not stopped by medication |
| Takata 34 | NA | c.2233C>T; p.Arg745* | NA | NA | DEE | NA | Developmental encephalopathy | NA |
Abbreviations: DEE, developmental epileptic encephalopathy; F, female; FS, febrile seizure; GTCS, generalized tonic‐clonic seizure; ID/DD, intellectual disability/developmental disorder; M, male; mon, month; NA, not available; SE, status epilepticus; TBS, Temple‐Baraitser syndrome; ZLS, Zimmermann‐Laband syndrome.