CLN8 disease
CLN8 disease is a rare, inherited neurodegenerative condition that presents in either a less-severe form (Northern epilepsy) or a more-severe, early-onset form.
Overview
CLN8 disease is an inherited disorder affecting the nervous system, classified as a type of neuronal ceroid lipofuscinosis (NCL) or Batten disease. The condition is categorized into two forms based on severity and life expectancy.
Symptoms
Less-Severe Form (Northern Epilepsy)
- Onset between ages 5 and 10.
- Recurrent seizures, often involving muscle rigidity and loss of consciousness.
- Gradual decline in intellectual function and coordination.
- Vision problems appearing in early to mid-adulthood.
- Individuals often live into late adulthood.
More-Severe Form
- Onset between ages 2 and 7.
- Myoclonic epilepsy (uncontrollable muscle jerks).
- Pronounced intellectual decline and loss of speech.
- Severe ataxia (difficulty walking and coordinating movements), eventually leading to immobility.
- Survival typically limited to late childhood or adolescence.
Causes
Mutations in the CLN8 gene cause the disease. The CLN8 protein is thought to assist in moving materials in and out of the endoplasmic reticulum and may regulate lipid levels in cells. In the more-severe form, the loss of CLN8 protein function leads to the accumulation of proteins and other substances in lysosomes, causing nerve cell death. The less-severe form is associated with very little cellular buildup, though the exact mechanism of cell death remains unclear.
Inheritance
CLN8 disease is inherited in an autosomal recessive pattern. Both copies of the CLN8 gene in each cell must have mutations for the condition to occur. Parents of an affected individual are carriers and typically do not exhibit symptoms.
Frequency
The less-severe form is primarily found in individuals of Finnish ancestry, particularly in the Kainuu region, where it affects approximately 1 in 10,000 people. The prevalence of the more-severe form is unknown.