Case Report: Epileptic phenotype in a patient with a MARK2 variant: the first detailed description and review of the literature

Background The gene encoding microtubule affinity-regulating kinase 2 ( MARK2 ) has recently been implicated in patients with autism spectrum disorder (ASD). Although seizures have been reported in 46.4% of a small cohort, detailed information regarding seizure phenotypes and longitudinal progression remains scarce. We present a case of MARK2 -related epilepsy and review previously reported cases in the literature. Case report and review An 11-year-old male patient with ASD carrying a heterozygous pathogenic variant (c.888 + 1G > A) in MARK2 gene experienced his first nocturnal tonic seizure at 5 years 11 months. Recurrent nocturnal focal impaired-consciousness seizures were accompanied by left temporal sharp waves on EEG, and episodes of focal status epilepticus were also noted. Oxcarbazepine provided only partial benefit, whereas perampanel effectively reduced nocturnal seizures and improved sleep initiation. He has remained seizure-free since 9 years 9 months on combined therapy. In our literature review, no prior reports described longitudinal changes in seizure manifestations, EEG evolution, or treatment response. EEG abnormalities were noted in 72.7% of patients (8/11), with focal epileptiform discharges being the most common finding ( N = 5). No major structural abnormalities were identified on brain MRI. Conclusion This case provides the first detailed clinical description of MARK2 -related epilepsy, characterized by focal seizures responsive to antiseizure medication.