8 GeneReviews® Management Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with DEPDCS-related epilepsy, the following evaluations are recommended: + Detailed clinical history to establish seizure type and frequency + Routine EEG + High-resolution brain MRI to evaluate for focal cortical dysplasia or other cortical malformation + Cognitive and behavioral assessment when problems are suspected based on focused medical history + Consultation with a clinical geneticist and/or genetic counselor Treatment of Manifestations ‘The response to antiepileptic drugs (AEDs) is variable. While some individuals respond well to first-line AEDs, others are more refractory to treatment. In four families with ADNFLE with a heterozygous DEPDC5 pathogenic variant, seven of nine individuals were drug resistant [Picard et al 2014], whereas in previous studies of individuals with ADNFLE, only one third of individuals were drug resistant. There is currently no evidence that seizures respond better to one particular AED. Attention should be paid to possible (long-term) side effects of AEDs. As in all patients with epilepsy, the goal should be to use as few AEDs as possible, in the lowest efficacious dose. In patients with focal cortical dysplasia, the possibility of epilepsy surgery should be explored early in the disease course. In one study, four of five unrelated individuals who underwent epilepsy surgery with resection of the focal cortical dysplasia had a favorable postoperative outcome [Baulac et al 2015]. Several of these individuals were part ofa larger family in which most family members had a history of focal epilepsy without FCD. Caregivers. For information on non-medical interventions and coping strategies for parents or caregivers of children diagnosed with epilepsy, see Epilepsy & My Child Toolkit. Surveillance Serial EEGs are appropriate when seizure frequency increases or when seizures of new symptomatology occur. Repeat brain MRI with a higher resolution technique is recommended in individuals with treatment-resistant, seizures whose first brain MRI was normal. Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. Therapies Under Investigation Since loss-of-function variants in DEPDCS are thought to lead to increased activation of the ml ORCI pathway, mTORC1 inhibitors including rapamycin (or everolimus) have been proposed as a potential targeted treatment option. So far, the clinical use of ms! ORCI inhibitors has only been studied in the more severe mL'ORopathy tuberous sclerosis, caused by pathogenic variants in TSC1 or TSC2. Further studies are needed to determine whether (subsets of) patients with DEPDCS could benefit from treatment with this class of drugs. Search Clinical Trials gov in the US and www:ClinicalTrialsRegister.cu in Europe for access to information on clinical studies for a wide range of diseases and conditions.