ORPHA: 98784; DO: 0060683;
Cytogenetic location: 15q24 Genomic coordinates (GRCh38) : 15:72,400,001-78,000,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 15q24 | Epilepsy, nocturnal frontal lobe, type 2 | 603204 | Autosomal dominant | 2 |
Nocturnal frontal lobe epilepsy-2 (ENFL2) is an autosomal dominant focal epilepsy syndrome characterized by childhood onset of clusters of motor seizures during sleep. Some patients may develop behavioral or psychiatric manifestations (summary by Derry et al., 2008).
For a general description and a discussion of genetic heterogeneity of ENFL, see ENFL1 (600513).
Derry et al. (2008) reported a large multigenerational family of English descent (family A) with nocturnal frontal lobe epilepsy associated in some with psychiatric disorders and cognitive impairment. The family had previously been reported as family C by Scheffer et al. (1995) and family M by Phillips et al. (1998). There were 11 affected individuals spanning 3 generations. Age at seizure onset ranged between 4 and 17 years, and all had partial nocturnal seizures. Seizures were typical of frontal lobe epilepsy, with dystonic posturing, prominent vocalization, and hypermotor automatisms. Four patients also had rare generalized tonic-clonic seizures, and 7 had rare partial diurnal seizures. Five patients had refractory seizures, and 2 had a history of status epilepticus. Three patients had depression, 1 had paranoid schizophrenia, and 1 had a behavioral disorder. One patient, aged 45 years old, showed developmental regression, intellectual disability, and neurologic abnormalities, including hemiparesis, ataxia, and extrapyramidal signs. This patient reportedly had over 100 seizures per night at the most active time, which was more than the other patients. Derry et al. (2008) excluded linkage to or mutations in several candidate genes, including CHRNA4 (118504), CHRNB2 (118507), and CHRNA2 (118502).
In a large family (family M) of English descent with autosomal dominant nocturnal frontal lobe epilepsy, Phillips et al. (1998) found linkage to chromosome 15q24 (maximum lod score of 3.01 at D15S152). The locus was close to the CHRNA3 (118503)/CHRNA5 (118505)/CHRNB4 (118509) gene cluster. This family had previously been reported as family C by Scheffer et al. (1995).
Derry et al. (2008) confirmed the locus on chromosome 15q24 in the family reported by Phillips et al. (1998) (maximum 2-point lod score of 3.21 at D15S205). However, the critical region identified by Derry et al. (2008) did not include the CHRNA3/4/5 gene cluster as originally reported. In addition, Derry et al. (2008) excluded mutations in coding regions of the CHRNA2 (118502) and CHRNB2 (118507) genes in this family.
Derry, C. P., Heron, S. E., Phillips, F., Howell, S., MacMahon, J., Phillips, H. A., Duncan, J. S., Mulley, J. C., Berkovic, S. F., Scheffer, I. E. Severe autosomal dominant nocturnal frontal lobe epilepsy associated with psychiatric disorders and intellectual disability. Epilepsia 49: 2125-2129, 2008. [PubMed: 18479385] [Full Text: https://doi.org/10.1111/j.1528-1167.2008.01652.x]
Phillips, H. A., Scheffer, I. E., Crossland, K. M., Bhatia, K. P., Fish, D. R., Marsden, C. D., Howell, S. J. L., Stephenson, J. B. P., Tolmie, J., Plazzi, G., Eeg-Olofsson, O., Singh, R., Lopes-Cendes, I., Andermann, E., Andermann, F., Berkovic, S. F., Mulley, J. C. Autosomal dominant nocturnal frontal-lobe epilepsy: genetic heterogeneity and evidence for a second locus at 15q24. Am. J. Hum. Genet. 63: 1108-1116, 1998. [PubMed: 9758605] [Full Text: https://doi.org/10.1086/302047]
Scheffer, I. E., Bhatia, K. P., Lopes-Cendes, I., Fish, D. R., Marsden, C. D., Andermann, E., Andermann, F., Desbiens, R., Keene, D., Cendes, F., Manson, J. I., Constantinou, J. E. C., McIntosh, A., Berkovic, S. F. Autosomal dominant nocturnal frontal epilepsy: a distinctive clinical disorder. Brain 118: 61-73, 1995. [PubMed: 7895015] [Full Text: https://doi.org/10.1093/brain/118.1.61]