The neuronal ceroid lipofuscinosis (NCL, or Batten disease) belongs to inherited neurodegenerative disorders with similar clinical manifestations like epileptic seizures, progressive psychomotor deterioration, and visual disturbance. Altogether NCLs are the most common neurodegenerative disease in children. The NCLs are inherited in an autosomal recessive pattern, and the first signs often can be found in childhood.
There are a few not so apparent terms at the beginning, so before we go any further, it is worth getting acquainted with them closer.
Neurodegenerative disorders are a broad group of diseases that characterizes the progressive loss of brain and spinal cord cells. Loss of cells (degeneration) causes all the symptoms. Although the final problem is the same, neurodegenerative disorders differ in the specific cause leading to it. Thus, some of them will develop faster and manifest other clinical signs. This may even be the case for one disease that has multiple genetic causes, and this is exactly the case with NCLs.
Autosomal recessive inheritance is gender independent (people of both sexes can become ill), and the risk of passing on a malfunctioning gene is at 50%. Each parent has two copies of each gene, and the offspring receives one randomly from each parent. One normal copy of a gene is enough for the body to function correctly. Generally, in diseases with recessive heredity, after the pathological gene is passed on, the condition will not be revealed because of the second correct copy of the gene. Thus, disease occurs if both parents are carriers of pathological gene copy, and each of them will pass it on. The chance of this situation is 25%.
The NCLs are identified worldwide, although their prevalence may differ from 1:1,000,000 in certain regions to 1:100,000 in Scandinavia.
NCL8 is one of NCLs types, caused by mutations in CLN8gene. CLN8mutations are described as a cause of Northern Epilepsy (NE) and late-infantile NCL variant (vLINCL). Northern Epilepsy (also known as progressive epilepsy with mental retardation - EPMR) can manifest with epilepsy, progressive mental deterioration, and cerebellar degeneration. This syndrome often occurs in northern Finland's population, hence the name. The second type of NCL8 - vLINCL, has a similar presentation, but, involuntary muscle twitching and retinal degeneration may be present. However, a recent report suggests that the CLN8mutations can also cause congenital NCL8 and atypical late infantile NCL.
To sum up - CLN8mutations cause NCL8 (type of neuronal ceroid lipofuscinosis). Additionally, NCL8 (depending on CLN8mutation) can manifest in four described to date (subtypes) clinical presentations - vLINCL, EPMR, congenital NCL8, and atypical late infantile NCL. Each subtype will differ in some way from others.
CLN8