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Disease Profile

Autosomal dominant nocturnal frontal lobe epilepsy

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

Adult

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ICD-10

-

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.

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)

ADNFLE; Epilepsy, nocturnal frontal lobe, 1; ENFL1;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is an uncommon, inherited form of epilepsy. People with ADNFLE have seizures that usually occur at night during sleep. Some people with ADNFLE also have seizures during the day. These seizures can last from a few seconds to a few minutes, and can vary from causing simple arousal from sleep, to dramatic muscle spasms and movements. The onset of ADNFLE ranges from infancy to adulthood, but most cases begin in childhood. Episodes tend to become milder and less frequent with age.[1][2] It is diagnosed based on symptoms and the results of tests such as an EEG. ADNFLE is inherited in an autosomal dominant manner and may be caused by a mutation in any of several genes. In most cases however, the genetic cause is not found. Seizures can usually be controlled with anti-seizure medications.[2]

Symptoms

The main symptom in people with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is seizures that generally occur at night. Seizures may begin anywhere from early childhood to adulthood, but most often begin in childhood.[3][4] Seizures may last from a few seconds to a few minutes.[1] The frequency of seizures varies from several per year to several per night.[3] Seizures may become less frequent or more mild as a person gets older.[1] Some people with ADNFLE occasionally have seizures while they are awake.[4] 

When a person with ADNFLE is having a seizure, they may experience a variety of movement-related symptoms ranging from mild to severe. Examples include:[1][3][4]

  • Short bursts of random, repetitive movements of the limbs, trunk, or head, lasting 2 to 4 seconds.
  • Brief, sudden arousal (waking), sometimes with repetitive movements, making sounds, crying, or feelings of fear.
  • Major attacks lasting 20 to 30 seconds, characterized by extreme stiffening of muscles, or movements such as pelvic thrusting, pedaling, twisting and writhing, or fast, forceful motions of the limbs.

Recurring episodes of exertion during the night may lead to sleepiness during the day.[4]

Most people with ADNFLE have normal intellect (thinking abilities), but in some cases, intellect is reduced. Some people with ADNFLE also have psychiatric disorders or behavior problems, but it is unclear if these are directly related to ADNFLE.[1][3]

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
5%-29% of people have these symptoms
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Childhood onset
Symptoms begin in childhood
0011463
Focal-onset seizure
Seizure affecting one half of brain
0007359
Incomplete penetrance
0003829

Diagnosis

A diagnosis of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is made based on signs and symptoms. In addition to the doctor taking a detailed medical and family history from the person with symptoms, obtaining information from others who see episodes occur is very helpful. In some cases, videoEEG monitoring during sleep is needed.

The features that suggest a diagnosis of ADNFLE include:

  • Clusters of seizures that occur mainly during sleep.
  • A normal neurologic exam and normal findings on brain imaging tests.
  • A normal EEG recorded during a seizure (ictal EEG), or one that is obscured by movement of the cables or electrodes.
  • An EEG recorded between seizures (interictal EEG) that shows few or no instances of patterns seen in people with epilepsy.
  • The presence of the same disorder in other family members, with evidence of autosomal dominant inheritance.

If ADNFLE is suspected, genetic testing may be ordered. However, genetic testing can confirm the diagnosis in only 20% of people with a family history of ADNFLE, and in fewer than 5% of people with no family history.[2]

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.

    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

        • Genetics Home Reference contains information on Autosomal dominant nocturnal frontal lobe epilepsy. This website is maintained by the National Library of Medicine.

          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.
          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • 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.

            References

            1. ADNFLE. Genetics Home Reference. April, 2009; https://ghr.nlm.nih.gov/condition/autosomal-dominant-nocturnal-frontal-lobe-epilepsy.
            2. Hirokazu Kurahashi and Shinichi Hirose. Autosomal Dominant Nocturnal Frontal Lobe Epilepsy. GeneReviews. February 19, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1169/.
            3. Hirose S, Kurahashi H. Autosomal dominant nocturnal frontal lobe epilepsy. Orphanet. December, 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=98784.
            4. Nobili L, Proserpio P, Combi R, et al. Nocturnal Frontal Lobe Epilepsy. Current Neurology and Neuroscience Reports. February, 2014; 14:424. https://link.springer.com/article/10.1007%2Fs11910-013-0424-6#Sec5.

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