What’s up, Doc? KCNT1-related epilepsy is a rare genetic cause of seizures

Jeff Hersh
·4 min read

Q: My neighbor’s son was just diagnosed with KCNT1 seizures, and they said it was a very rare disorder. Aren’t seizures fairly common in children?

A: The brain has many nerve cells that communicate with each other; a seizure occurs when there is an abnormal and excessive firing of electrical signals that interrupt these normal brain signals. There are several ways this may manifest (different types of seizures):

  • When a patient has a grand mal (generalized tonic-clonic) seizure, they typically have an abrupt loss of consciousness, and then will usually have "jerky" movements of the extremities, sometimes accompanied by loss of urine and/or stool.

  • Partial or focal seizures have localized symptoms; for example, they might affect just one arm. With simple partial focal seizures, the patient often has normal mentation throughout the episodes. With complex partial seizures, mentation is affected. This type of seizure may affect the frontal lobe and can cause alterations in thinking or behavior (and are therefore often called psychomotor seizures). These may be misdiagnosed as psychiatric problems.

  • With absence seizures, the patient will look out as if staring into space, not be responsive and even seem like they are daydreaming. This is much more common in children, and often resolves as the child matures. This may compromise school performance, and sometimes the child gets in trouble for "not paying attention."

Dr. Jeff Hersh
Dr. Jeff Hersh

You are correct; overall, seizures in children are not uncommon:

  • About 1 to 3 per 1,000 newborns will have a seizure (it may be more than that, as seizures in newborns may go unrecognized). The most common cause in newborns is insufficient oxygen to their brain (for whatever reason), and for premature infants the most common cause is bleeding into their brain.

  • Past the newborn period, seizures are even more common. One in 25 children will have at least one febrile seizure (a seizure associated with them having a fever, whether the fever if from a common childhood viral illness or other cause) in their lifetime. There are many other possible causes of seizures, including head/birth injuries, certain poisonings, metabolic issues (for example, prolonged low blood sugar from too much insulin given to a diabetic child), as well as certain genetic and/or hereditary conditions.

So having one or even a couple of seizures in childhood is not uncommon.

Epilepsy (seizure disorder) refers to a condition where a person has recurrent seizures due to a chronic underlying process. About 6 per 1,000 children have epilepsy, so unless you went to a very small school, the odds are that several people in your school had this condition. When their seizures can be well controlled with medication, the majority of these children lead normal lives, and it's likely you would never know they had epilepsy.

KCNT1-related epilepsy (so named because it is due to a mutation in the KCNT1 gene that encodes for the protein for potassium channels in the brain cells) is a rare genetic cause of seizures; it is diagnosed in 1 of every 2 million people annually. As with many genetic conditions, some cases of KCNT1-related epilepsy are inherited, so genetic counseling is part of the overall treatment for the patient and the family.

KCNT1-related epilepsy may manifest as:

  • KCNT1-related epileptic encephalopathy. Seizures typically start in early infancy, may be difficult to control even with multiple anti-seizure medications and may cause other complications including poor muscle tone, small head size, delayed milestones causing the child to learn to talk/walk later than a non-affected child or even making it so they are not able to achieve these milestones.

  • KCNT1-related frontal lobe epilepsy. Seizures for these children typically start later than for those with the epileptic encephalopathy variant, but usually by adolescence. Patients may have some degree of a delay or compromise of cognitive development, but usually are able to walk and talk fairly normally. Seizures may involve the frontal lobe and may occur during sleep, and so may seem similar to childhood night terrors. Some patients may also have abnormal blood vessels in their lungs, which can cause bleeding and lead to pulmonary complications.

The diagnosis of KCNT1-related epilepsy is suspected based on the history and physical examination. The typical childhood epilepsy workup may include brain imaging (MRI most commonly), electroencephalogram and possible other tests. A KCNT1-related epilepsy diagnosis may be verified by specific genetic testing.

Treatment of KCNT1-related epilepsy is aimed at controlling the seizures using anti-seizure medications, often including a "rescue" anti-seizure medication if needed. Patients who do not respond to aggressive medication treatments may be considered for device implants to directly stimulate certain nerves.

Unfortunately, the prognosis for some patients with KCNT1-related epilepsy may be poor, possibly with limited seizure control, developmental compromise, and/or with up to a 25% mortality during childhood.

Jeff Hersh, Ph.D., M.D., can be reached at DrHersh@juno.com.

This article originally appeared on MetroWest Daily News: KCNT1-related epilepsy is a rare genetic cause of seizures