CLN8-related neuronal ceroid lipofuscinosis (NCL8) is an inherited disorder marked by brain degeneration, leading to a progressive deterioration of cognitive and motor abilities.
Some individuals also experience seizures, and in certain cases, vision impairment. Within the spectrum of neuronal ceroid lipofuscinosis (NCL), the specific gene involved and the age of symptom onset differentiate various forms. Mutations in the CLN8 gene primarily give rise to variant late-infantile neuronal ceroid lipofuscinosis (vLINCL) or Northern epilepsy, also known as Progressive Epilepsy with Mental Retardation (EPMR).
vLINCL typically presents symptoms between ages 3 and 8, starting with epilepsy, vision loss, and motor control difficulties. Over time, both intellectual and motor skills decline, while epilepsy and vision impairment progressively worsen. In this form, life expectancy is typically limited, with individuals succumbing to the disease in late childhood or adolescence.
On the other hand, Northern epilepsy symptoms usually manifest between 5 and 10 years of age and predominantly consist of recurrent seizures and a gradual decline in cognitive function. After puberty, the frequency of seizures tends to decrease, and vision problems are infrequent. Individuals with Northern epilepsy often live into late adulthood, with some even surpassing the age of 60.
NCL8 is caused by pathogenic (disease-causing) variants in the CLN8 gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background.
Another names for this condition is neuronal ceroid lipofuscinosis 8.