Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a partial epilepsy with frontal lobe seizure semiology. It is characterized by childhood onset of frequent violent and brief motor seizures occurring at night. The disorder may be misdiagnosed as ... Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a partial epilepsy with frontal lobe seizure semiology. It is characterized by childhood onset of frequent violent and brief motor seizures occurring at night. The disorder may be misdiagnosed as night terrors, nightmares, hysteria, or paroxysmal nocturnal dystonia. The condition usually persists through adult life (Scheffer et al., 1994, 1995). The disorder is clinically distinctive and relatively homogeneous, although seizure severity and specific frontal lobe seizure manifestations vary within families (Hayman et al., 1997). - Genetic Heterogeneity of Nocturnal Frontal Lobe Epilepsy Nocturnal frontal lobe epilepsy is a genetically heterogeneous condition. See also ENFL2 (603204), which maps to chromosome 15q24; ENFL3 (605375), caused by mutation in the CHRNB2 gene (118507) on chromosome 1q21; ENFL4 (610353), caused by mutation in the CHRNA2 gene (118502) on chromosome 8p21; and ENFL5 (615005), caused by mutation in the KCNT1 gene (608167) on chromosome 9q34.
Scheffer et al. (1994) and Scheffer et al. (1995) reported 5 families from Australia, Britain, and Canada in which 47 members were affected with ADNFLE. The largest family contained 25 affected individuals spanning 6 generations. Onset was usually ... Scheffer et al. (1994) and Scheffer et al. (1995) reported 5 families from Australia, Britain, and Canada in which 47 members were affected with ADNFLE. The largest family contained 25 affected individuals spanning 6 generations. Onset was usually in childhood and the disorder persisted through adult life. The disorder was characterized by clusters of brief nocturnal motor seizures with hyperkinetic or tonic manifestations. Seizures occurred in clusters as patients dozed or shortly before awakening. Auras were often experienced, and patients were awake during the aura and seizures. Milder cases were often undiagnosed or misdiagnosed as nightmares or other sleep disorders, whereas more severely affected family members had frequent nocturnal seizures. All had normal psychomotor development and neurologic examination. Thomas et al. (1998) described one of the first European families with nocturnal frontal lobe epilepsy, including 5 affected individuals spanning 4 generations. In the most severely affected subject, NFLE had onset during the second month of life and persisted through adult life. Seizures were very frequent during infancy, although long-term evolution was relatively benign. Ictal video-EEG studies showed that attacks occurred in clusters during sleep and were partial seizures that were consistent with a frontal origin. Neuroimaging was normal. Carbamazepine was dramatically effective. Thomas et al. (1998) suggested that underestimation of cases is likely; the disorder in their family was perceived as a 'hereditary curse,' and consequently was concealed, including concealment from medical attention. Cho et al. (2003) reported a Korean family with ADNFLE in which 9 members from 3 generations were affected. The mean age at seizure onset was 11 years (range, 4 to 14 years). Seizure frequency ranged from 2 to 3 per year to 4 to 5 per night. All seizures arose from sleep, and no auras were reported. Episodes lasted about 20 to 40 seconds, and consisted of arm flexion, tonic head extension, mouth movements, and unintelligible speech. Ictal EEG and PET scans in some patients showed frontal lobe involvement. Unique features included mental retardation and poor response to carbamazepine.
In affected members of a large Australian kindred with ADNFLE reported by Scheffer et al. (1995) and Phillips et al. (1995), Steinlein et al. (1995) identified a mutation in the CHRNA4 gene (118504.0002).
In a Japanese ... In affected members of a large Australian kindred with ADNFLE reported by Scheffer et al. (1995) and Phillips et al. (1995), Steinlein et al. (1995) identified a mutation in the CHRNA4 gene (118504.0002). In a Japanese family with ADNFLE, Hirose et al. (1999) identified a ser252-to-leu mutation in the CHRNA4 gene (S252L; 118504.0004). Cho et al. (2003) identified the S252L mutation in a Korean family with ADNFLE. They noted that the clinical phenotype in the Korean family was similar to that reported in the Japanese family; shared features included mental retardation and drug resistance.