Globally, 3.5 million people are diagnosed with epilepsy annually, with childhood prevalence ranging from 41 to 187 cases per 100,000, peaking in the first year of life. Genetic factors contribute to the complex pathogenesis in 40–60% of cases. Early-onset epileptic encephalopathies (EIEEs), such as TMEM63A-related variants, lead to poor outcomes. A 4-year-old with genetically determined epileptic encephalopathy faced escalating seizures. Initial symptoms at three months included restlessness, tremors, and clonic eyelid convulsions, with abnormal myelination. Standard antiepileptic drugs provided temporary relief. Hospitalisation at 17 months involved prolonged seizures, abnormal laboratory results, and phenytoin use. At 2 years of age, an unconscious episode post-epileptic seizure, potentially triggered by a respiratory infection, was resolved with anti-inflammatory treatment. Three months later, a 2-hour seizure associated with fever and SARS-CoV-2 infection required intensive care, improving with elevated phenytoin dosage. In the latest hospitalisation, intravenous clonazepam and phenobarbital addressed increased seizure severity. Adjusted phenytoin dosage achieved therapeutic levels, leading to improved condition and discharge. The patient met the ILAE (International League Against Epilepsy) criteria for early epileptic encephalopathy (EIEE), revealing a TMEM63A variant causing transient hypomyelination. The symptoms, which included decreased muscle tone and nystagmus, mirrored reported cases with severe epileptic seizures. High-dose phenytoin, exceeding standard limits, was effective. The justification for higher doses prioritised the therapeutic benefits over any potential side effects.