KCNB1 Encephalopathy: signs and symptoms, etiology, epidemiology, diagnosis, and treatment

KCNB1 encephalopathy is a rare autosomal dominant disorder caused

First, the general overview

KCNB1 encephalopathy was first detected

2.

Due to the recent recognition of the syndrome and the limited number of patients with detailed clinical features, the full extent of the symptoms has not been described

In terms of epilepsy, most people with KCNB1 encephalopathy also have difficulty controlling seizures, usually in late infants to early childhood

3.

KCNB1 encephalopathy is caused by a change (mutation/mutation) in one copy of the KCNB1 gene that prevents it from working properly

Two types of KCNB1 variants have been identified in patients with KCNB1 encephalopathy

Of the largest cohort of 26 people, 20 (77%) had KCNB1 ion channel domain alias mutations, mainly concentrated in the S5 to S6 region

KCNB1 encephalopathy is an autosomal dominant disorder, which means that only one non-working copy of the gene causes the disease

4.

KCNB1 Encephalopathy is a very rare disease

5.

The symptoms of the following disorders may be similar

Early infantile epileptic encephalopathy (EIEE)/developmental and epileptic encephalopathy (DEE) is a broad class of disorders

Some patients with KCNB1 encephalopathy may also be diagnosed with Lennox-Gastaut syndrome (LGS

Rett syndrome is a progressive neurodevelopmental disorder with loss of developmental skills, motor abnormalities, autism spectrum disorder features, respiratory abnormalities, and swallowing problems
that primarily affect women.
Most cases of Rett syndrome are caused
by variants of MECP2.
Currently, KCNB1 is thought to cause mutations or atypical Rett syndrome in some patients
.

Landau-Kleffner syndrome is a rare childhood disorder that is accompanied by a severely abnormal EEG during sleep, leading to loss of language expression and language comprehension
.
The sleep EEG pattern of this disease is similar to that of status epilepticus (ESES) and/or sustained spike wave (CSWS) for slow-wave sleep, which has been diagnosed in some patients with KCNB1 encephalopathy who do not have seizures.

The following disorders may be associated
with KCNB1 encephalopathy as a secondary feature.
It is not necessarily part of the differential diagnosis:

Epilepsy is a chronic disease caused by repeated unprovoked seizures
caused by abnormal electrical activity in the brain.
There are many different causes of epilepsy, and sometimes the type of seizure may help determine the cause
.
Epilepsy may also occur in patients with other neurodevelopmental disorders
.
Epilepsy may also be a result of other genetic disorders, including Dravet syndrome, KCNQ2 encephalopathy, and Rett syndrome
.
Most patients with KCNB1 encephalopathy also have a diagnosis
of epilepsy.

Autism spectrum disorder is a neurodevelopmental disorder in which patients have difficulty communicating and interacting with people and have repetitive behaviors or limited interest
.
Together, these symptoms often make it difficult for you to function properly at home, at school, or at work
.
About half of patients with KCNB1 encephalopathy may also be diagnosed with autism spectrum disorder
.

6.
Diagnosis

The diagnosis of KCNB1 encephalopathy is carried out by molecular genetic testing
.
This is usually done through the epilepsy genome, which looks at many genes associated with epilepsy or sequences through an all-exome
.

Clinical testing and examination of
seizures is a clinical feature of most patients
.
EEG is highly recommended to help evaluate and guide the treatment
of seizures.
Even in patients who have not been diagnosed with seizures, nocturnal EEG that captures non-REM sleep can help look for frequent epileptic-like activity (such as continuous spikes in slow-wave sleep and status epilepticus in slow-wave sleep
).

A small number of patients have a critical QT interval
.
Screening
with an EKG or Holter monitor may be recommended.

7.
Treatment

Treatment usually requires a team of specialists, including a pediatrician, pediatric neurologist or paediatric epilepsy physician, developmental pediatrician, and/or other healthcare professional.

In children with seizures/epilepsy, anticonvulsants may help reduce the frequency of
seizures.
No clear anticonvulsant has been shown to be most helpful
in patients with KCNB1 encephalopathy.
In some patients, if the seizure cannot be controlled with medications, other treatments may be considered, including dietary therapy (ketogenic diet, modified Atkins diet), surgical implantation devices, or epilepsy surgery
.
Anticonvulsants may be recommended in some patients who do not have discrete seizures but have abnormal EEG activity during sleep
.

For children with autism spectrum disorder characteristics, a developmental pediatrician may be involved in the diagnosis and may recommend behavioral analysis (ABA) or other therapies
.

8.
Rare disease information registration

If you are willing to seek constantly updated information, it is recommended that you register the patient's information here, even if you are not fully diagnosed, you can register, click to enter:

Patient Information Registry System for Rare Diseases

Resources:

Torkamani, A.
, et al.
De novo KCNB1 mutations in epileptic encephalopathy.
Ann Neurol 2014; 76(4): 529-540.

de Kovel, C.
G.
F, et al.
Neurodevelopmental Disorders Caused by De Novo Variants in KCNB1 Genotypes and Phenotypes.
JAMA Neurol 2017:74(10):1228-1236.

Marini, C.
, et al.
Clinical features and outcome of 6 new patients carrying de novo KCNB1 gene mutations.
Neurol Genet 2017:3(6).

Kang, S.
K.
, et al.
High throughput Characterization of KCNB1 variants Associated with Developmental and Epileptic Encephalopathy.
BioRxiv 2019.

Online Mendelian Inheritance in Man (OMIM).
The Johns Hopkins University.
Epileptic Encephalopathy, Early Infantile, 26; EIEE26.
Entry No: 616056.
Last edited: 10/20/2014.
Accessed June 18, 2019.

National Institute of Mental Health (NIMH).
Autism Spectrum Disorder.
Last edited: March 2018.
  Accessed June 18, 2019.

JAMA Neurol: KCNB1 gene mutation and clinical nervous system phenotype