Neuronal Ceroid-Lipofuscinosis (CLN8-Related) (CLN8)
Neuronal ceroid-lipofuscinosis (CLN8-related) is an autosomal recessive neurodegenerative disorder that is caused by pathogenic variants in the gene CLN8. While it is found in different ethnicities around the world, it is more prevalent in individuals of Finnish descent due to the presence of a founder mutation. Most CLN8-caused neuronal ceroid-lipofuscinosis results in the late infantile form, in which symptoms begin between 2 and 7 years of age. Clinical features include progressive visual loss and neurologic symptoms, including seizures, ataxia, developmental and motor regression, and cerebral atrophy. Affected individuals usually lose independent ambulation within two years of disease onset. Most patients with the late-infantile form of neuronal ceroid-lipofuscinosis do not survive beyond early adulthood. Some patients with pathogenic CLN8 variants do not develop neuronal ceroid-lipofuscinosis but instead develop a disorder known as Northern epilepsy, where seizures begin between the ages of 5 to 10 and result in a progressive intellectual disability. Specific variants result in the development of either Northern epilepsy or neuronal ceroid-lipofuscinosis, and therefore the phenotype may be predicted based on the patient’s genotype.
For information about carrier frequency and residual risk, please see the Expanded Carrier Screen brochure.