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Disease Profile

Lafora disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Adolescent

ICD-10

G40.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Lafora body disorder; Epilepsy progressive myoclonic 2; EPM2;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

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. Treatment is based on the signs and symptoms present in each person.[1][2][3]

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.[2]

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.[1][2]

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.[1][2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
100% of people have these symptoms
Lafora bodies
0100318
30%-79% of people have these symptoms
Ataxia
0001251
Confusion
Disorientation
Easily confused
Mental disorientation

[ more ]

0001289
Dementia
Dementia, progressive
Progressive dementia

[ more ]

0000726
Depressivity
Depression
0000716
Dysarthria
Difficulty articulating speech
0001260
Emotional lability
Emotional instability
0000712
Erratic myoclonus
0025357
Generalized myoclonic seizure
0002123
Giant somatosensory evoked potentials
0001312
Headache
Headaches
0002315
Hypsarrhythmia
0002521
Inability to walk
0002540
Nasogastric tube feeding
0040288
Recurrent aspiration pneumonia
0002100
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Status epilepticus
Repeated seizures without recovery between them
0002133
Visual hallucinations
0002367
5%-29% of people have these symptoms
Atonic seizure
0010819
Atypical absence seizure
0007270
Bilateral tonic-clonic seizure with focal onset
0007334
Brain atrophy
Brain degeneration
Brain wasting

[ more ]

0012444
Focal impaired awareness seizure
0002384
Focal sensory seizure with visual features
0011165
Hepatic failure
Liver failure
0001399
Severe photosensitivity
Severe sun sensitivity
0007537
Sleep disturbance
Difficulty sleeping
Trouble sleeping

[ more ]

0002360
Vegetative state
0031358
Percent of people who have these symptoms is not available through HPO
Apraxia
0002186
Autosomal recessive inheritance
0000007
Cutaneous photosensitivity
Photosensitive skin
Photosensitive skin rashes
Photosensitivity
Sensitivity to sunlight
Skin photosensitivity
Sun sensitivity

[ more ]

0000992
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Generalized non-motor (absence) seizure
Brief seizures with staring spells
0002121
Myoclonus
0001336
Progressive neurologic deterioration
Worsening neurological symptoms
0002344
Psychosis
0000709
Rapidly progressive
Worsening quickly
0003678
Visual loss
Loss of vision
Vision loss

[ more ]

0000572

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). 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.[1]

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.[2][3]

GeneReview's Web site offers more specific information regarding the diagnosis of Lafora disease. Please click on the link to access this resource.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    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.[2][3]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • MedlinePlus Genetics contains information on Lafora disease. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Lafora disease. Click on the link to view a sample search on this topic.

            References

            1. Lafora progressive myoclonus epilepsy. Genetics Home Reference. July 2009; https://ghr.nlm.nih.gov/condition/lafora-progressive-myoclonus-epilepsy.
            2. Anna C Jansen, MD, PhD and Eva Andermann, MD, PhD, FCCMG. Progressive Myoclonus Epilepsy, Lafora Type. GeneReviews. January 2015; https://www.ncbi.nlm.nih.gov/books/NBK1389/#lafora.Clinical_Description.
            3. Monaghan TS, Delanty N. Lafora disease: epidemiology, pathophysiology and management. CNS Drugs. July 2010; 24(7):549-561.

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