User:Monibea11/proposal.draft

Synopsis

Early Childhood
Northern Epilepsy Syndrome causes recurrent seizures between the ages of five to ten. These seizures, that may last up to 15 minutes, can be classified mostly as tonic-clonic, but partial seizures could also occur. Generally, the recurrence is one to two times per month. In the years following the onset of seizures, a noticeable decrease in intellectual capacity.

Adolescence
During puberty, seizure frequency increases to one to two times per week. The mental function has a rapid decline which can be seen by a lack of coordination, failure to complete education, as well as fine motor activities. In rare cases, some suffered from loss of vision.

Adulthood
Seizure frequency is reduced to four to six per year. By this time they are mentally and physically incapable to live without assistance due to the total mental degradation. Life expectancy is at least 50 years of age but overall their life expectancy is shorter than the average worldwide age of 70.

Genetics
Northern epilepsy syndrome is caused by an inherited recessive autosomal mutation in the “telomeric region of the short arm of chromosome 8”. There are at least ten mutations within the chromosome and the most common missense mutation occurs at codon 24, where a glycine takes the place of an arginine. This primary mutation can also be paired with a missense at codon 237, where an arginine takes the place of a glycine. When the two mutations interact a lengthened progression of the disease is observed. The primary mutation (Arg24Gly) creates the protein CLN8. One in every 135 of Finnish descent were reported to be a carrier of the mutation.

Pathophysiology
An accumulation of transmembrane proteins has been seen in the brain tissue of northern epilepsy patients. This protein is a 286 amino acid transmembrane protein that has not been identified before, meaning its unique to Northern Epilepsy Syndrome. CLN8 has been linked to the accumulation of subunit c of mitochondrial ATP synthase and a small amount of sphingolipid activator proteins in the neurons. β-amyloid is also seen in this protein accumulation.

Diagnosis
By sampling a patient’s blood DNA from can be tested with a ABI Big Dye Terminator v.3.0 kit. The DNA sequence taken from it can be run with CLN8 Sanger Sequencing or CLN8 Targeted Familial Mutations whether its single, double, or triple Exon Sequencing. Also, preliminary evidence of the disease can be detected by means of MRI and EEG.

Treatment
Current available treatment is limited to affecting the symptoms, not the cause. Seizure frequency can be regulated by the use of drugs such as Clonazepam and Sodium Valproate. Clonazepam has been effective in minimising seizure activity, especially during puberty.