Hippocampal sclerosis worsens autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) phenotype related to CHRNB2 mutation

Background and purpose Autosomal dominant nocturnal frontal lobe epilepsy ( ADNFLE ) is a distinct epileptic syndrome with a broad range of severity even amongst affected members of the same pedigree, and the level of pharmacoresistance may reach 30%, close to that seen in sporadic focal epilepsies. Methods To investigate this issue of phenotypic heterogeneity, we prospectively carried out a high‐resolution 3‐T magnetic resonance imaging ( MRI ) study in an ADNFLE family containing 10 affected members including one pharmacoresistant patient and carrying the V287L mutation of the CHRN beta2 subunit ( CHRNB 2). MRI studies were evaluated in a manner blinded to the electro‐clinical data. Results The brain MRI showed normal results in all affected individuals except the 22‐year‐old right‐handed woman (member III‐7) who had refractory seizures and typical radiological signs of left hippocampal sclerosis. She also had a simple febrile seizure at the age of 10 months. Conclusion The results of this study illustrate that hippocampal sclerosis has offered a fertile substrate for intractable ADNFLE to develop. The present findings also highlight the importance of acquired factors that are directly relevant to the epilepsy phenotype and its severity even in monogenic epilepsies.