Most children with HCN1 variants have epilepsy, a condition of the brain characterized by episodes called seizures. Patients with HCN1 variants often have different kinds of seizures, but most of them affect the whole brain (generalized seizures) although focal seizures (i.e. seizures restricted to limited brain areas) exist in some patients. During a generalized seizure patients lose body control and usually consciousness with the environment followed by general muscular rigidity, then jerking of the limbs. Some patients have ‘minor’ attacks and only present with a loss of consciousness (like a blank stare) and motor function for few seconds (Absences). Patients might also have focal seizures with loss of consciousness, motor arrest, reach a tonic posturing, and manifest jerking of part of the body like one arm or leg or eyelids. Apnoea and cyanosis can also be observed by skin colour during or at the end of the seizure. Fever (for example, due to an infection, illness or after vaccination) is a trigger of seizures in about half of the patients. The frequency of the seizures is variable from one child to the other and can be as frequent as several a day or be limited to a few seizures per year. 60% of patients with HCN1 variants have seizures that are resistant to anti-epileptic drugs and continue having seizures despite treatment with multiple drugs.
Approximately 70% of patients have a variable degree of intellectual disability ranging from mild to moderate or severe intellectual disability whereas autistic traits are more rare. Patients who are severely impaired are unable to sit, stand or walk independently, speech is absent.