Genetics of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)

Nocturnal frontal lobe epilepsy (NFLE) is a heterogeneous clinical syndrome characterized by clusters of hyperkinetic motor seizures of frontal semiology appearing from sleep, which vary in intensity and duration. The onset of the epilepsy is usually during childhood or adolescence and the disorder is lifelong but not progressive. NFLE manifestations can improve after puberty, but there is a marked clinical variability and some patients also experience seizures in old age. The clinical neurologic examination is almost always normal, as well as neuroimaging. Rare exceptions are represented by patients presenting focal brain computed tomography or magnetic resonance abnormalities. A few cases can show positive risk factors for epilepsy (e.g. birth anoxia, febrile convulsions, or head injury), and stress, sleep deprivation, and menstruation can be triggering factors in some patients. The seizures often appear nightly and in clusters, but they can have a variable frequency, ranging from a few attacks per month to several per night. Up to a third of patients present with occasional secondarily generalized seizures or rare seizures during wakefulness [1,2]. Patients can complain of diurnal symptoms such as tiredness and sleepiness due to the sleep integrity disruption caused by the epileptic episodes, especially in patients experiencing many episodes per night. Patients with NFLE show seizures with variable manifestations that, on the basis of the different presentations in intensity and duration, can be classified into three main types: paroxysmal arousals (PA), nocturnal paroxysmal dystonia (NPD), and episodic nocturnal wanderings (ENW). There is a characteristic and marked intraindividual stereotypy that is usually maintained over the years, and frequently a marked autonomic activation is a common finding during the seizures. Few patients can present only a single type of seizure, and different seizures tend to overlap in the same patient, the briefest ones often being the initial part of a more prolonged attack.