Authors: Dorottya B. Kacsoh, University of Central Florida College of Medicine 
Alison L. Christy, MD, PhD, Providence Pediatric Neurology at St. Vincent Medical Center—Portland, Oregon
David Bearden, MD, MSCE, University of Rochester School of Medicine—Rochester, New York 

Reviewed: April 2023 

SUMMARY 

KCNT1-related epilepsies are a group of epilepsies. They are caused by a variation in the KCNT1 gene. The seizures are often difficult to control.  

Most children will have:  

• Developmental delay  
• Intellectual disability 

The conditions are lifelong.  

Disorder Overview

DESCRIPTION

There are two main KCNT1-related epilepsies. They are: 

• Epilepsy of infancy with migrating focal seizures (EIMFS).  
• Sleep-related hypermotor epilepsy (SHE). This used to be called autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).  

In both conditions, children generally do not have problems with development until seizures begin.  

Rarely, children may have a mild focal epilepsy without intellectual disability.  

SIGNS AND SYMPTOMS

EIMFS (Epilepsy of infancy with migrating focal seizures) 

In EIMFS, seizures start within the first six months of life. Once seizures start, infants stop developing. They may even lose developmental milestones. Seizures can occur daily.  

Other symptoms may include:  

• Autonomic instability. Affected individuals may:  
  • Have a fast or slow heart rate. 
  • Turn blue. 
  • Sweat 
  • Stop breathing.  
• Hypotonia (floppy muscles).  
  • Muscle tone is low in infants.   
  • However, as children get older, many will have increased tone in their arms and legs. 

• Movement disorders. 
• Microcephaly. The head is small.  
• Abnormal blood vessels in the lungs. These vessels may cause significant bleeding. 
• Abnormal heart rhythms. This is rare.  

SHE (Sleep-related hypermotor epilepsy) 

In SHE, seizures begin after the first six months of life and before adolescence. Developmental milestones may regress. This can be mild or moderate.  

Most seizures occur during sleep. However, daytime seizures can occur. They may be present in up to one third of children.  

Other symptoms may include: 

• Behavioral and psychiatric symptoms. Children may have: 
  • Autism spectrum disorder  
  • Depression 
• Learning disabilities. 

Occasionally, KCNT1-related epilepsies may present differently. Other types of seizures beyond EIMFS and SHE may occur.  

Most children with this condition have many types of seizures. There is a risk of status epilepticus. This is a prolonged seizure. It may lead to brain damage or death.  

CAUSES

KCNT1-related epilepsies are caused by a variation in the KCNT1 gene. This variation causes a particular channel to be too active. Brain cells send too many signals. It is not well understood why some children with KCNT1 variations develop EIMFS and others develop SHE. 

KCNT1-related epilepsies are inherited in an autosomal dominant pattern. This means that only one different copy of the gene is needed to cause symptoms. 

Almost all cases of EIMFS are due to new genetic variations. Rarely, a parent may have the mutation in only some of their cells. This pattern is called mosaicism. In some cases, a parent with SHE may have a child with EIMFS. 

Most cases of SHE occur because of new variations. However, SHE may be inherited from an affected parent. If one parent has SHE, all children have a 50% chance of developing KCNT1-related epilepsy. The type of epilepsy in the child may be either SHE or EIMFS. 

LABORATORY INVESTIGATIONS

Genetic testing will show a variation in the KCNT1 gene.  

Types of testing include: 

TREATMENT AND THERAPIES

EIMFS does not respond well to traditional anti-seizure medications. No single medication has been shown to be the most effective for all patients. Some patients respond well to the ketogenic diet.  

It is important to note that most children with EIMFS will continue to have seizures, regardless of treatment. However, with treatment, they may experience fewer seizures. 

Some patients have a type of seizure called infantile spasms.  

SHE usually responds well to traditional anti-seizure medications. However, some patients with SHE need multiple medications. 

Children with EIMFS will require:  

• Physical therapy 
• Occupational therapy 
• Speech therapy 

OUTLOOK

In both conditions, seizures may decrease over time. Because of the frequency of seizures, a rare complication called sudden unexpected death in epilepsy (SUDEP) may occur. For more information on this topic, see our SUDEP Resource page.  

In EIMFS, nearly all children have profound intellectual disability. Many will never be able to speak or walk. EIMFS has a higher mortality than SHE.  

In SHE, many children will have intellectual disability, autism spectrum disorder, or psychiatric issues such as anxiety and depression. This can be mild or moderate. These patients will generally be able to speak and walk. They may be able to live relatively independently. It depends on the severity of SHE. 

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