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I Am A Medical Professional

 

WE ARE YOUR KCNQ2 RESOURCE

 

This is the portal for medical professionals to find the most up-to-date information about KCNQ2-related epilepsy. The goal is to provide an overview of available information on this emerging condition. If you have a patient with a potential or documented case of KCNQ2-related epilepsy, you’ll discover how to connect with researchers who are studying the condition and encourage your patient’s family to enroll in a study. We believe a collaborative approach is key to accelerating progress.

The KCNQ2 community is small, but it is growing. We are here to identify, support, and promote the work of researchers who are making headway toward new treatments and, ultimately, a cure. If there are additional resources you would like to find or share here, or if you have any other questions or comments, please contact us at info@kcnq2.org. This portal is a work in progress, and we would be glad to have your input.

 

Mutations in KCNQ2 can cause a clinical spectrum of epilepsy from benign to severe, referred to collectively as KCNQ2-related epilepsy.  In 1964, Drs. Rett and Teubel described an inherited neonatal-onset epilepsy syndrome based on observations from a single family.  Seizures typically began shortly after birth, remitted in the infantile period, and were usually followed by normal development.  The term “Benign Familial Neonatal Convulsions” (BFNC) was introduced a few years later.  In 1998, mutations in KCNQ2 were identified as the cause of epilepsy in these families.  Reports of more severe presentations of seizures and intellectual disability associated with KCNQ2 were published from 2003-2007.  In 2012, Weckhuysen et al. reported novel KCNQ2 mutations in previously undiagnosed infants with epileptic encephalopathy.  Since then, several case series of ‘KCNQ2 encephalopathy’ were published from centers around the world, and our understanding of this condition continues to grow.

Clinicians should consider KCNQ2-related epilepsy in neonates with seizure onset in the neonatal period (usually first week of life) and without a definite cause.  Seizures are typically tonic and can have autonomic symptoms.  Although the seizure types at onset are similar, there are electroclinical features that help differentiate the self-limited BFNE form from the more severe KCNQ2 encephalopathy.

Benign Familial Neonatal Epilepsy (BFNE):

  • Seizure onset in the first week of life in a normal, otherwise healthy, neonate.
  • Interictal EEG background is continuous.
  • Family history of neonatal onset seizures (autosomal dominant inheritance).
  • Seizures remit off anticonvulsants during infancy and rarely recur.
  • Long-term developmental outcome is usually normal or favorable.

KCNQ2 Encephalopathy:

  • Seizure onset in the first week of life without identifiable cause.
  • EEG is abnormal at the onset with a discontinuous appearance, typically burst-suppression pattern, and/or multi-focal epileptiform discharges.
  • Neonatal presentation may be consistent with Early Myoclonic Encephalopathy (EME) and/or Ohtahara Syndrome.
  • Seizures are refractory in the infantile period and largely come under control (with anticonvulsants) after approximately 1 to 3 years old.
  • EEG will evolve over weeks to months from burst-suppression pattern to a more continuous background with multi-focal epileptiform discharges.
  • Intellectual impairment ranges from mild to profound, and many patients do not walk or talk.  Some patients show signs of autistic spectrum disorder.
  • Seizures due to BFNE are most often controlled with short-term treatment with a standard anticonvulsant, such as phenobarbital.
  • Seizures due to KCNQ2 encephalopathy are initially refractory to initial standard anticonvulsant therapy.   Some patients are reported to respond better to sodium channel blockers such as phenytoin and carbamazepine.
  • Ezogabine is a new anticonvulsant that can increase the KCNQ2 channel function.  Since this drug is only FDA approved for use in adults with focal epilepsy, use in infants and children is very limited.  This and other potassium channel opener drugs may be useful to control seizures and possibly improve developmental outcome in severe KCNQ2 encephalopathy.
  • In addition to EEG, the standard evaluation for the etiology of new onset neonatal seizures might include neuroimaging and laboratory testing of blood, urine, and CSF.
  • If other immediately identifiable causes of neonatal onset seizures, including pyridoxine-dependency, are ruled out and the electroclinical presentation is consistent with the KCNQ2-related epilepsy spectrum, then genetic testing may help confirm the diagnosis.
  • Testing strategies may vary based on availability in different institutions. Two commonly available options are single gene testing (KCNQ2 sequence analysis and/or deletion/duplication testing) or Next-Generation Sequencing (NGS) panels that include multiple genes associated with epilepsy including KCNQ2.
  • Note that there are cases of BFNE reported with mutations in KCNQ3.
  • Refer your patient with suspected or confirmed KCNQ2-related epilepsy to the RIKEE project (Rational Intervention for KCNQ2 Epileptic Encephalopathy), a database developed by Dr. Edward Cooper at Baylor. The RIKEE project aims to collect patient data to uncover correlations between specific mutations and phenotypic expression.
  • The Jack Pribaz Foundation seeks to support KCNQ2 research. Download our Process for Applying for Grant Funding information sheet. Learn how to submit your Letter of Intent.
  • Join the KCNQ2 LinkedIn group to stay on top of the latest research.
  • If you have questions or comments, please don’t hesitate to contact us at info@kcnq2.org.