Genetic Epilepsy

Gene: KCNQ2

Green List (high evidence)

PMID 25959266: Benign neonatal variants are usually inherited from affected parents, while EIEE are de novo and more severe

Missense reported for both conditions, PTCs almost only reported in patients with benign neonatal seizures (PMID: 32917465)

Missense variants - Dominant negative
OMIM, PMID 24318194- Functional analysis of missense shows reduced channel currents and dramatic slowing of activation upon depolarization. Impairs the function of dimers
PTCs - LOF

Reduced penetrance:
- Well reported for benign neonatal seizures, which tends to remit with age. Patients with BFS have a higher susceptibility of seizures recurring late in life
- Unaffected carriers can pass on variants to severely affected children, which could due to mosaicism

Created: 13 Nov 2020, 7:39 a.m. | Last Modified: 13 Nov 2020, 7:39 a.m.

Panel Version: 0.898

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epileptic encephalopathy, early infantile, 7, 613720; Seizures, benign neonatal, 1, 121200

Publications

• 25959266
• 32917465
• 24318194

Mode of pathogenicity
Other

Green List (high evidence)

PMID 25959266: Benign neonatal variants are usually inherited from affected parents, while EIEE are de novo and more severe

Missense reported for both conditions, PTCs almost only reported in patients with benign neonatal seizures (PMID: 32917465)

Missense variants - Dominant negative
OMIM, PMID 24318194- Functional analysis of missense shows reduced channel currents and dramatic slowing of activation upon depolarization. Impairs the function of dimers
PTCs - LOF

Reduced penetrance:
- Well reported for benign neonatal seizures, which tends to remit with age. Patients with BFS have a higher susceptibility of seizures recurring late in life
- Unaffected carriers can pass on variants to severely affected children, which could due to mosaicism

Created: 13 Nov 2020, 3:41 a.m. | Last Modified: 13 Nov 2020, 3:41 a.m.

Panel Version: 0.5357

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Epileptic encephalopathy, early infantile, 7, 613720; Seizures, benign neonatal, 1, 121200; Myokymia, 121200

Publications

• PMID 25959266
• 32917465
• 24318194

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice

I don't know

Episodic ataxia feature of mouse model phenotype, and reported as part of the phenotype in one case

Created: 16 Jan 2020, 11:07 p.m. | Last Modified: 16 Jan 2020, 11:07 p.m.

Panel Version: 0.33

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Early infantile epileptic encephalopathy 7, MIM#613720

Publications

• 22169383
• 20962009
• 10575255