Periventricular nodular heterotopia (PVNH) is a neuronal migration disorder often associated with drug-resistant epilepsy. The epileptogenic zone network (EZN) in PVNH is generally large, contraindicating surgery. Stereoelectroencephalography (SEEG) can be proposed to map the EZN and perform radiofrequency thermocoagulation (THC) with an efficacy rate of approximately 65%. There are genetic forms of PVNH, particularly with mutations in the filamin A gene (FLNA). However, data on SEEG-guided THC in these patients still have not been described. We report four patients with FLNA-positive PVNH who underwent SEEG-guided THC. All were women with several types of seizures and psychiatric comorbidities. EZN was extensive and often bilateral, including a part of the heterotopias. The outcomes of SEEG-guided THC varied
two patients experienced significant seizure reduction and improvement in psychiatric symptoms (Engel class I-II), one showed partial improvement (Engel class III), and one had no significant benefit (Engel class IV). Psychiatric comorbidities, including posttraumatic stress disorder, depression, and anxiety, were present in all cases, with some patients showing symptom improvement alongside seizure reduction. Despite genetic origin, SEEG-guided THC can be proposed in FLNA-positive PVNH-related epilepsy, although outcomes vary. The presence of FLNA mutations should not contraindicate surgical intervention but may influence the therapeutic response. Further research is needed to understand the impact of genetic variants on epilepsy outcome.