Genes Do Not Read DSM: Tuberous Sclerosis Complex May Dominate with Multi-Neuropsychiatric Symptoms

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder frequently accompanied by epilepsy and TSC-associated neuropsychiatric disorders. Psychiatric-predominant seizure presentations may, however, delay recognition. This clinical challenge describes a 26-year-old woman with recurrent panic-like episodes characterized by dyspnea, choking sensations, palpitations, and derealization, followed by depressive symptoms. The episodes persisted despite treatment with selective serotonin reuptake inhibitors and benzodiazepines. Further examination revealed hypomelanotic macules, prompting neurologic and systemic evaluation. Brain imaging demonstrated findings consistent with cortical tubers and subependymal nodules, while video electroencephalography captured frequent focal seizures without impaired awareness arising from the left frontotemporal region. Positron emission tomography/computed tomography identified a corresponding frontal abnormality. Although genetic testing detected a nonclassical TSC1 variant, the TSC diagnosis was established on clinical grounds. Treatment with lacosamide eliminated detectable epileptiform activity and substantially reduced the frequency and severity of her panic-like episodes; depressive and anxiety symptoms also improved with combined lacosamide and duloxetine treatment. This case illustrates how focal seizures involving frontal, temporal, and limbic-autonomic networks may mimic primary panic disorder. Stereotyped, brief, recurrent, and treatment-refractory psychiatric episodes-particularly when accompanied by neurocutaneous findings-should prompt electroencephalography and brain imaging. The case also emphasizes that an uninformative or uncertain genetic result does not exclude clinically established TSC or alter recommended surveillance and multidisciplinary management.