HomeGeneticsConditionAutosomal dominant sleep-related hypermotor epilepsy
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Autosomal dominant sleep-related hypermotor epilepsy
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Autosomal dominant sleep-related hypermotor epilepsy

Autosomal dominant sleep-related hypermotor epilepsy is a rare genetic form of epilepsy characterized by brief, complex seizures that occur primarily during sleep. These episodes typically begin in childhood or adolescence and involve sudden, repetitive motor activities.

Overview

Sleep-related hypermotor epilepsy (SHE) is a form of epilepsy characterized by seizures that typically begin while a person is sleeping. The seizures often appear during childhood or adolescence and involve varying degrees of muscle (motor) activity, which can include large, complex, and repetitive movements, known as hyperkinetic seizures. Autosomal dominant sleep-related hypermotor epilepsy (ADSHE) is a specific form of SHE that runs in families. The features of ADSHE can vary widely, even among members of the same family.

Symptoms and Clinical Features

People with ADSHE typically experience focal seizures, which start in a specific region of the brain. These seizures often occur in clusters during nonrapid eye movement (non-REM) sleep. They typically begin and end abruptly, with each seizure lasting no more than 2 minutes. Symptoms can range from mild to complex motor activities:

  • Minor motor activity that may simply wake a person from sleep
  • Repetitive motor activity, such as flinging or throwing motions of the arms and bicycling movements of the legs
  • Muscle stiffness or abnormal body positions
  • Getting out of bed and wandering around, which can be mistaken for sleepwalking
  • Rapid breathing (hyperventilation), a sense of breathlessness, and vocalizations such as moaning or crying

Upon waking from sleep, some individuals with ADSHE experience an aura—a pattern of unusual feelings or sensations that warns them of an oncoming seizure. Auras in ADSHE can include:

  • Numbness
  • Shivering
  • A sense of fear
  • Dizziness (vertigo)
  • A feeling of falling or being pushed

Seizures typically develop before the age of 20 years, and the episodes tend to become milder and less frequent over time. While many individuals effectively manage their seizures with medication, approximately 30 percent of affected individuals have seizures that become resistant to medication. Additionally, psychiatric disorders, behavioral problems, and intellectual disabilities have been reported in some individuals with ADSHE, though it remains unclear if these features are directly related to the seizures or the underlying genetic cause.

Frequency

SHE is an uncommon form of epilepsy, affecting about 1.8 out of every 100,000 individuals. More than 100 families with ADSHE have been reported in the medical literature.

Causes and Genetic Factors

ADSHE is caused by pathogenic variants (mutations) in one of several different genes. A genetic cause can be identified in approximately 19 percent of people with the condition, while in the majority of cases, the cause remains unknown.

Associated Genes

  • CHRNA4, CHRNA2, and CHRNB2: These genes provide instructions for making subunits of the nicotinic acetylcholine receptor (nAChR) complex. This complex acts as a channel allowing ions (calcium, sodium, and potassium) to cross cell membranes, playing a vital role in chemical signaling between neurons. Pathogenic variants can make these channels more sensitive, altering neuron communication and triggering abnormal brain activity. Variants in the CHRNA4 gene are the most common of these, found in approximately 6 percent of people with ADSHE.
  • DEPDC5, NPRL2, and NPRL3: These genes provide instructions for proteins that make up the GATOR1 complex, which regulates the mTOR pathway involved in cell metabolism, growth, and division. Variants in these genes disrupt GATOR1 function, leading to an overactive mTOR pathway, increased nerve cell activation, and seizures. Variants in each of these genes account for approximately 5 to 7 percent of ADSHE cases.
  • KCNT1: This gene belongs to a family that provides instructions for making potassium channels, which generate and transmit electrical signals. Pathogenic variants typically increase ion flow across these channels, contributing to neuron excitation and seizures. Approximately 1 percent of people with ADSHE have a variant in this gene.
  • Other genes, such as CABP4 and CRH, have also been associated with the condition.

Inheritance Pattern

ADSHE is inherited in an autosomal dominant pattern, meaning one copy of the altered gene in each cell is sufficient to cause the disorder. However, the condition exhibits reduced penetrance, as only 60 to 80 percent of individuals who inherit a pathogenic variant develop signs and symptoms.

Most affected individuals have an affected parent. Other cases are described as sporadic, occurring in people with no family history of the disorder. These sporadic cases may result from new (de novo) variants that occur during the formation of reproductive cells or during early embryonic development.

Other Names for This Condition

  • ADNFLE
  • ADSHE
  • Autosomal dominant nocturnal frontal lobe epilepsy
  • Autosomal dominant sleep-related hypermotor (hyperkinetic) epilepsy
  • ENFL
  • Nocturnal frontal lobe epilepsy
  • Sleep-related hypermotor epilepsy

Frequently Asked Questions

DSHE follows an autosomal dominant inheritance pattern, meaning that a person with the condition has a 50 percent chance of passing the genetic mutation to each child. However, the condition exhibits variable expressivity, which means that even if a child inherits the gene, the severity of symptoms can range from very mild to severe, and some individuals may have fewer or less frequent seizures than their parents. Genetic counseling is recommended for families to understand these probabilities and the potential for variable outcomes.
Many individuals with ADSHE experience auras just before or upon waking from a seizure. Common auras include a sudden sense of fear, dizziness, shivering, or numbness in specific parts of the body. Some patients report a feeling of breathlessness or hyperventilation. Recognizing these specific sensory or emotional changes can help caregivers and patients identify the onset of a seizure cluster, allowing for quicker intervention or documentation for the medical team.
DSHE seizures typically involve more intense and repetitive motor activity than typical sleepwalking, such as bicycling leg movements, flinging arms, or getting out of bed and wandering with a sense of urgency. While night terrors involve screaming and intense fear, ADSHE seizures often include specific auras like numbness, shivering, or a sudden sense of fear before the motor activity begins. Additionally, ADSHE seizures are brief, usually lasting less than two minutes, and occur in clusters during non-REM sleep, whereas sleepwalking episodes can last longer and are less likely to involve complex, repetitive motor patterns.
Sodium valproate is generally considered the first-line treatment for sleep-related hypermotor epilepsy, including the autosomal dominant form. However, because ADSHE is a genetic condition, clinicians may also consider other antiseizure medications like levetiracetam or lacosamide if valproate is not tolerated or effective. It is important to note that some medications, such as carbamazepine, may worsen symptoms in some patients, so medication selection should be guided by a neurologist experienced in this rare epilepsy syndrome.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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