What are the other Names for this Condition? (Also known as/Synonyms)

• Ceroid lipofuscinosis neuronal 8
• Neuronal Ceroid Lipofuscinosis, Northern Epilepsy Variant
• Progressive Epilepsy-Intellectual Disability Syndrome, Finnish type

What is Northern Epilepsy? (Definition/Background Information)

• Northern Epilepsy is a rare condition that affects the nervous system
• Signs and symptoms of the condition generally develop between ages 5 and 10 years and may include recurrent seizures, mild intellectual disability, and motor abnormalities (i.e. problems with coordination and balance). Some affected people may also experience decreased visual acuity
• Northern Epilepsy is caused by changes (mutations) in the CLN8 gene and is inherited in an autosomal recessive manner
• Treatment options are limited to therapies that can help relieve some of the symptoms

(Source: Northern Epilepsy; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Northern Epilepsy? (Age and Sex Distribution)

• Northern Epilepsy is a rare inherited disorder. The onset of symptoms may occur between the ages of 5 and 10 years
• Both males and females may be affected by this disorder
• The condition is predominantly reported in Northern Finland

What are the Risk Factors for Northern Epilepsy? (Predisposing Factors)

• A positive family history may be an important risk factor, since Northern Epilepsy can be inherited
• Being of northern Finnish descent

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Northern Epilepsy? (Etiology)

• Northern Epilepsy is caused by mutations in the CLN8 gene, which localizes to the short arm of chromosome 8
• This gene codes for a protein located on the cell membrane. The exact function of this protein is not known
• The condition is inherited in an autosomal recessive manner

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Northern Epilepsy?

The signs and symptoms of Northern Epilepsy may include:

• Ataxia
• Cerebellar atrophy
• Cerebral atrophy
• Curvilinear intracellular accumulation of autofluorescent lipopigment storage material
• Delayed speech and language development
• Increased neuronal autofluorescent lipopigment
• Myoclonus
• Seizures

Based on the frequency of symptoms observed, the following information may be noted:

Very frequently present symptoms in 80-99% of the cases:

• Clumsiness
• EEG abnormality
• Focal seizures with impairment of consciousness or awareness
• Generalized tonic-clonic seizures
• Progressive visual loss
• Restlessness

Frequently present symptoms in 30-79% of the cases:

• Developmental regression
• Intellectual disability
• Mental deterioration
• Psychosis

(Source: Northern Epilepsy; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Children with Northern Epilepsy are often normal in infancy and early development, till the condition manifests when they are between 5 and 10 years old.

How is Northern Epilepsy Diagnosed?

Northern Epilepsy is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm causative gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Northern Epilepsy?

The complications of Northern Epilepsy may include:

• Risk of falls and injury due to seizures
• Severe intellectual deficiency
• Loss of skills learned
• Vision loss
• Negative impact on quality of life

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Northern Epilepsy Treated?

There is no cure for Northern Epilepsy, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. The treatment methods may include:

• Medications for controlling epilepsy
• Special education
• Medications for any psychiatric disorder that may develop
• Psychological counseling

How can Northern Epilepsy be Prevented?

Currently, Northern Epilepsy may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Northern Epilepsy? (Outcomes/Resolutions)

• The prognosis of Northern Epilepsy is dependent upon the severity of the signs and symptoms and associated complications, if any
• The condition is characterized by slow cognitive decline, which may affect an affected individual’s quality of life. However, life expectancy is not severely reduced, and those with this condition may live beyond 50 years of age
• The prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Northern Epilepsy:

Northern Epilepsy may be also known by the following terms:

• CLN8 Disease, EPMR (subtype)
• CLN8 Disease, Late Infantile (subtype)
• CLN8 Disease, Northern Epilepsy Variant
• NCL, Northern Epilepsy Variant
• Neuronal Ceroid lipofuscinosis 8 (CLN8)
• Progressive Epilepsy-Intellectual Disability, Finnish type

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/