Northern epilepsy syndrome

Northern epilepsy syndrome, also called progressive epilepsy with mental retardation, is a rare inherited disease and a subtype of neuronal ceroid lipofuscinosis. It is counted among the Finnish heritage diseases and, unlike most of them, has been reported only in Finland, where about one in 10,000 people from the northern Kainuu region have it. Seizures begin in childhood, usually between the ages of five and ten, and are mostly tonic-clonic, lasting up to fifteen minutes. They become more frequent at puberty and then ease in adulthood, but intellectual ability declines through these years and affected adults generally cannot live without assistance. The disease is inherited in an autosomal recessive way and is caused by mutations in the CLN8 gene on the short arm of chromosome 8, the most common being a substitution at codon 24 in which glycine replaces arginine. About one in 135 people of Finnish descent carries the mutation. CLN8 protein accumulates in brain tissue, along with subunit c of mitochondrial ATP synthase. Diagnosis rests on finding the gene mutation, supported by MRI and EEG findings. Nothing has been found to stop the progression, and treatment aims at seizure control with drugs such as clonazepam and sodium valproate. Life expectancy is only moderately reduced, and patients usually survive past 40 to 50 years of age. It was not first recognised as a neuronal ceroid lipofuscinosis; that came in 1999, when it was found to be the first disease caused by mutations in the CLN8 gene.