HCN1 is a gene located on chromosome 5 that codes for a protein able to assemble itself into four subunits that altogether form a channel transporting positive ions in neuronal cells. This channel has peculiar properties, which allows neurons to control their level of excitability.
Clinical features
The first epileptic seizures usually appear during infancy or childhood and can be associated with development delay, that over time leads to delays in milestones and intellectual disability. The severity of the epilepsy, developmental delay and intellectual disability varies from one child to the other and depends on the type and location of the variant on the HCN1 channel.
Prevalence
This condition is a very rare disorder and so far, only a few patients (less than 50) have been diagnosed worldwide.
Inheritance
Chromosome and their genes come in pairs, one in each pair is inherited from the person’s mother and the other from their father. When one of the genes is altered by a genetic variant, the child carrying this variant may develop epilepsy. Since only one chromosome with the HCN1 variant is sufficient for developing the disease, it can be passed on to the next generation according to dominant inheritance. However, many affected children have unaffected parents, because the HCN1 variant is new in them (de novo mutation). In this case, the variant has likely occurred in the HCN1 gene of either parent’s cell at conception.