Funding transnational collaborative research through joint transnational calls is one of the major objectives of E-Rare. This is the most important and effective joint activity to enhance the cooperation between European scientists working on rare diseases and thus reducing the fragmentation of research in this field. E-Rare launches calls on a yearly basis. The topic and eligibility criteria are specified every year and therefore may vary from one call to the other.

Benign Familial Neonatal Seizures (BFNS) as disease model for human idiopathic epilepsies: expansion of the genotype-phenotype correlations and insights into novel disease mechanisms

Project Coordinator

IRCCS Bambino Gesù Children's Hospital


Alvaro Villaroel Universidad del Pais Vasco Unidad de Biofisica CSIC-UPV/EHU Leioa, Spain
Holger Lerche University of Ulm Neurological Clinic and Institute of Applied Physiology Ulm, Germany
Rima Nabbout Hôpital Necker-Enfants Malades University of Paris V Paris, France

Publications of the EUROBFNS project

Major results of the project

Benign Familial Neonatal Seizures syndrome (BFNS) is a rare form of epilepsy that affects newborns. It is characterized by recurrent epileptic seizures that begin in the first days of life and remit spontaneously after few weeks or months. This disorder is age-dependent and genetically determined and may affect different member of a family. Mutations in two genes have been identified in patients with BFNS, EBN1 (20q13.3) and EBN2 (8q24), encoding respectively for KCNQ2 and KCNQ3, two neuronal potassium channels genes that are responsible for the regulation of excitability of the neuronal cells. While this particular form of epilepsy is self-limiting, we believe that understanding its mechanisms can teach us something relevant to the pathogenesis of more common epilepsy types that affect so many people. Indeed, potassium channels appear as an emerging target for pharmacological interventions directed against human hyperexcitability diseases, including epilepsy. Indeed, Retigabine is a new anti-epileptic drugs that acts by opening the neuronal potassium channels. Retigabine is in late-stage development for the treatment of focal seizures in adult patients and is considered as a promising effective and safe therapy for children with epilepsy. EUROBFNS is a collaborative translational research project. Our study was designed to integrate the research done in the laboratory and the research done in the clinical setting toward the development of new therapies for epilepsy.
The main aim of this project was to expand the clinical and genetic knowledge of a rare disease such as BFNS, in order unravel the complex relationship existing between potassium channels malfunctioning and clinical manifestations in BFNS-affected patients. Our European network includes clinical researchers and basic scientists. By working together, we were able to identify novel genetic abnormalities in BFNS families, to expand clinical knowledge of this disorder through genotype-phenotype correlations. By understanding the structural implications of the gating changes prompted by BFNS-causing mutations we were able to define the functional consequences of these mutations on the regulation of potassium channels. We believe that understanding the specific molecularaspects of this peculiar disorder will lead to novel pharmacological compounds for treating refractory epilepsies in both children and adults.

We were able to structure a European network that is now in place and serve as a crossroad for data and samples collection, sceering and follow-up of affected families. We achieved a critical mass of patients and studied them by sequencing for mutations KCNQ2 and KCNQ3. Patients who tested negative were tested for deletions by MLPA (Multiplex Ligationdependent Probe Amplification). Novel mutations have been characterized electrophysiologically and we could demonstrate that a dynamic developmental reorganization at a molecular level takes place in the first weeks of life, accounting for the transient epileptic phenotype in these patients.

E-Rare 2012 - Created by Toussaint Biger