KCNT1-related Epilepsy Diagnosis

Finding out that your child has a KCNT1 gene mutation is a troubling emotional experience, and it can be overwhelming for a parent trying to understand all the new information. All children are different and can vary widely in their symptoms. We aim to provide families with information to help you get the best care possible from the very beginning, because important decisions are made soon after diagnosis.  

We cannot provide medical advice but can suggest what topics to discuss with your healthcare providers. We have a network of parents who have children living with KCNT1 who support one another. Please reach out to us if you need help or have any questions.    

What is KCNT1

KCNT1 is a channel that affects the flow of electricity in the brain and sometimes in the heart. This channel is found throughout the body, and mutations in KCNT1 result in increased electrical flow through the potassium channels. This primarily results in problems in electric electrical activity in the brain, which can cause seizures. KCNT1-related epilepsy syndromes: 1) early onset seizures, either epilepsy of infancy with migrating focal seizures EIMFS, also known as migrating partial seizures of infancy MMPSI, or 2) it can cause an epileptic encephalopathy (EE). There is also 3) a later onset form of KCNT1 related epilepsy which is often known as Sleep-related Hypermotor Epilepsy, formerly known as autosomal dominant nocturnal frontal lobe epilepsy ADNFLE.. KCNT1 is also expressed in the heart and in the blood vessels coming out of the heart. And this can sometimes result in cardiac arrhythmias or inabnormal blood vessels that go from the heart to the lungs. Those are called aorta, pulmonary collaterals. Reports have identified children who exhibit symptoms of both, while some people carry a gene mutation but have no seizures. Other syndromes associated with KCNT1 can include Ohtahara and West syndromes.

Some people are carriers and have no symptoms. If you have a genetic test with KCNT1 you should speak with a genetic counselor.

EIMFS or MMPSI– Onset Before 6 Months

Seizures often begin before 6 months of age and increase in frequency and severity, negatively impacting neurodevelopment and often resulting in regression and severe developmental disabilities. Other names: Epilepsy of Infancy with Migrating Focal Seizures (EIMFS), Early Infantile Epileptic Encephalopathy, MMPSI or Migrating Partial Epilepsy of Infancy. Seizures may be difficult to detect but the child may get hiccups, stop breathing, turn blue, or sweat moderately. Seizures in EIMFS are resistant to medication and can progress to nearly continuous by age six to nine months. This can result in prolonged seizures or status epilepticus.

Sleep-Related Hypermotor Epilepsy (SHE) (formally known as ADNFLE) – Onset After 6 Months

The KCNT1 mutation can cause clusters of nocturnal seizures that vary from simple arousals to very physical thrashing movements. These seizures happen during sleep and can bemistaken as night terrors. This phenotype is referred to as Sleep-Related Hypermotor Epilepsy (SHE) , formerly known as Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE) seizures typically start later than EIMFS. Download clinician handout here.

Diagnosis

The diagnosis is established in a patient with intractable epilepsy and with identification of a heterozygous pathogenic variant in KCNT1 through genetic testing from a certified lab. The patients with EIMFS/MMPSI syndrome are most often de novo KCNT1 mutations, and most with SHE/ANDFLE are inherited from one parent. Several genetic testing companies include the KCNT1 gene in their epilepsy panels but when possible, we recommend whole genome or whole Exome testing of the affected child and the parents.. It is preferred that genetic tests are certified by the American Board of Medical Genetics and Genomics.

Treatment

Treatment for KCNT1-related epilepsy initially focuses on reducing or stopping the number of seizures. Unfortunately many traditional anti-convulsant medications don't work very well so you must work with your physician to try different options. The types of seizures experienced by these children are so variable that surgical intervention is not an option although some patients have vagus nerve stimulating (VNS) device surgically implanted with limited success. Many parents report that a ketogenic diet is one of the most effective ways to reduce seizures followed by Phenobarbital, Topamax Tegretol. Quinidine has been used as an off-label anticonvulsant with success in some patients, but careful monitoring is necessary due to possible negative effects on the heart. Some parents report some improvement with cannabidiol but there is not sufficient research in this area. In addition to reducing seizures, treatments focus on addressing symptoms that are often associated with low muscle tone and sedation from the medications. These can create issues with feeding and swallowing, gastrointestinal difficulties, constipation, urinary tract issues. Often parents are faced with a decision ofwhether to supplement their child's nutrients through the placement of a temporary feeding tube, or amore permanent G-tube. Some children have issues with their heart and lungs, particularly the development of potentially dangerous blood vessels called major aortic and pulmonary collaterals that must be carefully monitored to ensure they do not rupture. In some cases of pulmonary collaterals embolization is recommended. Breathing issues and managing oral secretions can also be an issue. Sleep apnea and seizures during sleep require monitoring with different devices and alarms. Parents also must consider special beds, supportive chairs, and standing walkers to aid the development of bones and muscles. Creative parents and therapists have adapted toys, tables, and devices to find ways to provide entertainment for their children as well as a means of stimulating cognitive and visual development. Caring for the special needs of your child requires a great deal of effort but having a coordinated medical team and supportive community can help parents affectively manage their child's care. More treatment guidelines are available at the link below.

Downloadable KCNT1 Information Sheets