Seizures, benign familial neonatal, 2; BFNS2

Disease ID:138
Name:Seizures, benign familial neonatal, 2; BFNS2
Associated with:1 target
Synonyms
Benign familial neonatal seizures | Benign neonatal seizures
Database Links
Disease Ontology: DOID:14264
OMIM: 121201
Orphanet: ORPHA1949

Targets

Kv7.3
Role:  Also known as epilepsy, benign neonatal type 2 (EBN2). BFNC2 is an autosomal dominant form of epilepsy in the newborn that clears spontaneously after a few weeks and is followed by normal psychomotor development.

Defects in KCNQ3 are the cause of benign familial neonatal convulsions type 2 (BFNC2). Late occurrence of seizures and intellectual deficiency may also be present in some families carrying KCNQ3 mutations. An association between a very rare single nucleotide polymorphism located in the C-terminal region of Q3 with autism spectrum disorders.
Drugs:  Retigabine, flupirtine
Side effects:  For retigabine: chills, pain, symptomatic hypotension, dizziness, nausea, myalgia, sweating, vomiting, asthenia and somnolence. For flupirtine: drowsiness, dizziness, dry mouth, pruritis and nausea.
Therapeutic use:  Retigabine and flupirtine have shown antiepileptic activity in humans and in a broad range of seizure models in rodents. Retigabine and flupirtine may possess actions unrelated to KCNQ opening. It is unclear, therefore, if the efficacy of retigabine and flupirtine in animals models of epilepsy and pain and in human studies is entirely due to KCNQ activation.
Comments:  Receptor blockers enhance learning and memory in animal models. KCNQ openers also have potential for the treatment of other CNS disorders characterized by neuronal hyperexcitability, such as migraine, and neuropathic pain.
References:  1-4,6-7
Mutations:  Kv7.3 is associated with 2 mutation. Click here for details

Ligands

No ligand related data available for Seizures, benign familial neonatal, 2; BFNS2

References

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1. Charlier C, Singh NA, Ryan SG, Lewis TB, Reus BE, Leach RJ, Leppert M. (1998) A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family. Nat. Genet., 18 (1): 53-5. [PMID:9425900]

2. Coghlan MJ, Carroll WA, Gopalakrishnan M. (2001) Recent developments in the biology and medicinal chemistry of potassium channel modulators: update from a decade of progress. J. Med. Chem., 44 (11): 1627-53. [PMID:11356099]

3. Gilling M, Rasmussen HB, Calloe K, Sequeira AF, Baretto M, Oliveira G, Almeida J, Lauritsen MB, Ullmann R, Boonen SE et al.. (2013) Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum Disorders. Front Genet, 4: 54. [PMID:23596459]

4. Schroeder BC, Kubisch C, Stein V, Jentsch TJ. (1998) Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy. Nature, 396 (6712): 687-90. [PMID:9872318]

5. Singh NA, Westenskow P, Charlier C, Pappas C, Leslie J, Dillon J, Anderson VE, Sanguinetti MC, Leppert MF. (2003) KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum. Brain, 126 (Pt 12): 2726-37. [PMID:14534157]

6. Soldovieri MV, Boutry-Kryza N, Milh M, Doummar D, Heron B, Bourel E, Ambrosino P, Miceli F, De Maria M, Dorison N et al.. (2014) Novel KCNQ2 and KCNQ3 mutations in a large cohort of families with benign neonatal epilepsy: first evidence for an altered channel regulation by syntaxin-1A. Hum. Mutat., 35 (3): 356-67. [PMID:24375629]

7. Wua YJ, Dworetzky SI. (2005) Recent developments on KCNQ potassium channel openers. Curr. Med. Chem., 12 (4): 453-60. [PMID:15720253]