Severe autosomal dominant nocturnal frontal lobe epilepsy associated with psychiatric disorders and intellectual disability

Department of Medicine (Neurology), Epilepsy Research Centre, University of Melbourne, Victoria, Australia.
Epilepsia (Impact Factor: 4.57). 06/2008; 49(12):2125-9. DOI: 10.1111/j.1528-1167.2008.01652.x
Source: PubMed


Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a relatively benign epilepsy syndrome with few comorbidities. Here we describe two families with unusually severe ADNFLE, with associated psychiatric, behavioral, and cognitive features. Detailed clinical data on 17 affected individuals were obtained, and genotyping of microsatellite markers, linkage analysis, and sequencing of candidate genes was performed. The severe ADNFLE phenotype in these families was often refractory to treatment, with status epilepticus occurring in 24% of subjects. Psychiatric or behavioral disorders occurred in 53%, with intellectual disability in 24%, and developmental regression in two individuals. No mutations were identified in alpha4, alpha2, or beta2 nAChR subunits. In one family there was evidence of linkage to a region of 15q24 without nAChR subunit genes. In conclusion, severe ADNFLE has significant medical, psychiatric, and intellectual morbidity. The molecular basis of severe ADNFLE is unknown but may involve non-nAChR-related mechanisms.

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Available from: Christopher P Derry, Mar 25, 2015
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    • "Autosomal dominant nocturnal frontal lobe epilepsy is a focal seizure that occurs predominantly during sleep with a typical onset in late childhood. The mean age among more than 110 patients reported in six different case reports was 10.9 years (Table 3; Scheffer et al., 1995; Oldani et al., 1998; Phillips et al., 1998; Nakken et al., 1999; Derry et al., 2008; Heron et al., 2012). ADNFLE patients are sometimes misdiagnosed as having sleep disorders rather than suffering a seizure attack, because the seizure attacks often disrupt sound sleep (Oldani et al., 1998). "
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    • "Nocturnal frontal lobe epilepsy (NFLE) is a focal epilepsy starting in childhood and persisting into young adulthood. Affected individuals are typically of normal intelligence, but rare cases with intellectual disability and ⁄ or psychiatric disorders have been reported (Derry et al., 2008). Sporadic and familial forms of NFLE do not show clinical differences (Combi et al., 2004). "
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