Autosomal dominant nocturnal frontal lobe epilepsy and mild memory impairment associated with CHRNB2 mutation I312M in the neuronal nicotinic acetylcholine receptor

• Published in: Epilepsy & behavior 2008-08, Vol.13 (2), p.361-365
• Main Authors: Cho, Yong-Won, Yi, Sang-Doe, Lim, Jeong-Geun, Kim, Dae-Kwang, Motamedi, Gholam K
• Format: Article
• Language: English
• Subjects: Acetylcholine receptor; Adult; Alleles; Amino Acid Substitution; CHRNB2; Chromosome Aberrations; Codon - genetics; Diagnosis, Differential; DNA Mutational Analysis; Epilepsy; Epilepsy, Frontal Lobe - diagnosis; Epilepsy, Frontal Lobe - genetics; Female; Frontal Lobe - physiopathology; Genes, Dominant - genetics; Genetic Carrier Screening; Genetic Testing; Gyrus Cinguli - blood supply; Humans; Isoleucine - genetics; Membrane Proteins - genetics; Memory; Memory Disorders - diagnosis; Memory Disorders - genetics; Methionine - genetics; Middle Aged; Mutation, Missense; Neurogenetics; Neurology; Neuropsychological Tests; Nocturnal frontal lobe epilepsy; Nocturnal Paroxysmal Dystonia - diagnosis; Nocturnal Paroxysmal Dystonia - genetics; Paroxysmal nocturnal behavior; Pedigree; Phenotype; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Polysomnography; Receptors, Nicotinic - genetics; Regional Blood Flow - physiology; Seizure
• ISSN: 1525-5050; 1525-5069
• DOI: 10.1016/j.yebeh.2008.04.017

Abstract Certain paroxysmal nocturnal behaviors have been established as features of nocturnal frontal lobe epilepsy (NFLE). Despite insight into its genetics, the majority of patients with NFLE are not linked to a known mutation and clinical diagnosis remains a challenge. We describe a family presenting with stereotyped nocturnal arousals from non-rapid eye movement sleep, bilateral hand posturing, and pelvic thrusting in the mother, but subtle motor activity in the daughter, and minimal or no epileptiform EEG discharges. Despite normal IQ, there were moderate and severe verbal memory deficits in the mother and daughter, respectively. Genetic testing revealed the CHRNB2 mutation I312M in transmembrane region 3 (M3) of the neuronal nicotinic acetylcholine receptor. Phenotypic similarities in unrelated families suggest the determining role of this mutation in NFLE, whereas different inter- and intrafamilial cognitive profiles point to other factors. The absence of clear motor features of NFLE in the daughter emphasizes the shortcomings of current clinical criteria and the potential for genetic testing to further guide clinical diagnostic criteria.