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

• Epilepsy Progressive Myoclonic 2 (EPM2)
• Lafora Body Disorder
• Myoclonic Epilepsy of Lafora (MELF)

What is Lafora Disease? (Definition/Background Information)

• Lafora Disease is an inherited, severe form of progressive myoclonus epilepsy. The condition most commonly begins with epileptic seizures in late childhood or adolescence
• Other signs and symptoms include difficulty walking, muscle spasms (myoclonus), and dementia. Affected people also experience rapid cognitive deterioration that begins around the same time as the seizures. The condition is often fatal within 10 years of onset
• Most cases are caused by changes (mutations) in either the EPM2A gene or the NHLRC1 gene and are inherited in an autosomal recessive manner
• The treatment of Lafora Disease is based on the signs and symptoms present in each person

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

Who gets Lafora Disease? (Age and Sex Distribution)

• Lafora Disease is a very rare congenital disorder, affecting about 1-9 in a million individuals
• The presentation of symptoms may occur in late childhood or adolescence
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Lafora Disease? (Predisposing Factors)

• A positive family history may be an important risk factor, since Lafora Disease can be inherited
• Currently, no other risk factors have been clearly identified for the disorder

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 Lafora Disease? (Etiology)

Most cases of Lafora Disease are caused by changes (mutations) in either the EPM2A gene or the NHLRC1 gene. These genes encode proteins that play a critical role in the survival of nerve cells (neurons) in the brain.

• Although the proteins are thought to have many functions in the body, one important role is to help regulate the production of a complex sugar called glycogen (an important source of stored energy in the body)
• Mutations in the EPM2A gene or the NHLRC1 gene interfere with the production of functional proteins, leading to the formation of Lafora bodies (clumps of abnormal glycogen that cannot be broken down and used for fuel) within cells
• A buildup of Lafora bodies appears to be especially toxic to the cells of the nervous system and leads to the signs and symptoms of Lafora Disease

Lafora Disease is inherited in an autosomal recessive manner.

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

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 Lafora Disease?

The signs and symptoms of Lafora Disease may include:

• Isolated febrile or non febrile convulsions in infancy or early childhood
• Recurrent seizures, which may include generalized tonic-clonic seizures, occipital seizures (which can cause temporary blindness and visual hallucinations) and myoclonic seizures
• Signs of cognitive decline, including
• Behavioral changes
• Depression
• Confusion
• Ataxia (difficulty controlling muscles)
• Dysarthria
• Dementia
• Abnormality of metabolism/homeostasis
• Absence seizures
• Apraxia
• Cutaneous photosensitivity
• Dementia
• Gait disturbance
• Generalized myoclonic seizures
• Generalized tonic-clonic seizures with focal onset
• Hepatic failure
• Myoclonus
• Progressive neurologic deterioration
• Psychosis
• Simple partial occipital seizures
• Visual auras
• Visual hallucinations
• Visual loss

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

How is Lafora Disease Diagnosed?

• A diagnosis of Lafora Disease is often suspected based on the presence of characteristic signs and symptoms
• An EEG and an MRI of the brain are generally recommended in all people with recurrent seizures and are useful in investigating other conditions in the differential diagnosis
• Additional testing can then be ordered to confirm the diagnosis and rule out other conditions that may cause similar features. For example, a skin biopsy may be performed to detect "Lafora bodies" (clumps of abnormal glycogen that cannot be broken down and used for fuel) which are found in most people with the condition
• Genetic testing for changes (mutations) in either the EPM2A gene or the NHLRC1 gene may be used to confirm the diagnosis in some cases

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

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 Lafora Disease?

The complications of Lafora Disease may include:

• Progressive and hard to treat epileptic attacks
• Rapid decline in cognition
• Blindness
• Inability to move, incapacitation

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

How is Lafora Disease Treated?

There is no cure for Lafora Disease, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develop. The treatment methods may include:

• Anti-seizure medications
• Use of a feeding tube to help with proper nutrition

How can Lafora Disease be Prevented?

Currently, Lafora Disease 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
• Certain drugs (Example: phenytoin) may trigger myoclonic seizures, and can be avoided to reduce their occurrence 
• 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 Lafora Disease? (Outcomes/Resolutions)

• The prognosis for individuals affected by Lafora Disease is poor
• It is reported that the mean survival period following onset of symptoms is about 10 years

Additional and Relevant Useful Information for Lafora Disease:

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

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