Lafora disease

Alternate names

Lafora body disorder; Epilepsy progressive myoclonic 2; EPM2; Myoclonic epilepsy of Lafora; MELF

Definition

Lafora disease is an inherited, severe form of progressive myoclonus epilepsy. The condition most commonly begins with epileptic seizures in late childhood or adolescence.

Epidemiology

• The prevalence of Lafora progressive myoclonus epilepsy is unknown.
• Although the condition occurs worldwide, it appears to be most common in Mediterranean countries (including Spain, France, and Italy), parts of Central Asia, India, Pakistan, North Africa, and the Middle East.

Cause

• 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).

Gene mutations

• 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 build up 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.

Inheritance

Autosomal recessive inheritance, a 25% chance

• Lafora disease is inherited in an autosomal recessive manner.
• This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Signs and symptoms

• The signs and symptoms of Lafora disease generally appear during late childhood or adolescence.
• Prior to the onset of symptoms, affected children appear to have normal development although some may have isolated febrile or nonfebrile convulsions in infancy or early childhood.
• The most common feature of Lafora disease is recurrent seizures.
• Several different types of seizures have been reported including generalized tonic-clonic seizures, occipital seizures (which can cause temporary blindness and visual hallucinations) and myoclonic seizures.
• These seizures are considered "progressive" because they generally become worse and more difficult to treat over time.
• With the onset of seizures, people with Lafora disease often begin showing signs of cognitive decline.
• This may include behavioral changes, depression, confusion, ataxia (difficulty controlling muscles), dysarthria, and eventually, dementia. By the mid-twenties, most affected people lose the ability to perform the activities of daily living; have continuous myoclonus; and require tube feeding and comprehensive care.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

100% of people have these symptoms

• Lafora bodies

30%-79% of people have these symptoms

• Ataxia
• Confusion(Disorientation)
• Dementia(Dementia, progressive)
• Depressivity(Depression)
• Dysarthria(Difficulty articulating speech)
• Emotional lability(Emotional instability)
• Erratic myoclonus
• Generalized myoclonic seizure
• Giant somatosensory evoked potentials
• Headache(Headaches)
• Hypsarrhythmia
• Inability to walk
• Nasogastric tube feeding
• Recurrent aspiration pneumonia
• Spasticity(Involuntary muscle stiffness, contraction, or spasm)
• Status epilepticus(Repeated seizures without recovery between them)
• Visual hallucinations

5%-29% of people have these symptoms

• Atonic seizure
• Atypical absence seizure
• Bilateral tonic-clonic seizure with focal onset
• Brain [[atrophy](Brain degeneration)
• Focal impaired awareness seizure
• Focal sensory seizure with visual features
• Hepatic failure(Liver failure)
• Severe photosensitivity(Severe sun sensitivity)
• Sleep disturbance(Difficulty sleeping)
• Vegetative state

Diagnosis

• A diagnosis of Lafora disease is often suspected based on the presence of characteristic signs and symptoms.
• 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.
• 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.

Treatment

• Unfortunately, there is currently no cure or way to slow the progression of Lafora disease.
• Treatment is based on the signs and symptoms present in each person.
• For example, certain medications may be recommended to manage generalized seizures.
• In the advanced stages of the condition, a gastrostomy tube may be placed for feeding.
• Drugs that are known to worsen myoclonus (i.e. phenytoin) should be avoided.

Prognosis

• The long-term outlook (prognosis) for people with Lafora disease is unfortunately poor.
• There is currently no cure for the condition and it is considered progressive (symptoms worsen over time).
• By the mid-twenties, most affected people lose the ability to perform the activities of daily living; have continuous myoclonus; and require tube feeding and comprehensive care.
• On average, affected people survive approximately 10 years after the onset of symptoms.

NIH genetic and rare disease info

• NIH info on Lafora disease

Lafora disease is a rare disease.

Lafora disease Resources
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