A 10-month-old boy began having prolonged hemiclonic seizures triggered by fever at 5 months of age. He has since developed multiple afebrile generalized and myoclonic seizures refractory to two antiepileptic drugs, with developmental slowing. Both carbamazepine and phenytoin clearly worsened his seizures. Mutation of which gene is most likely responsible?

• A SCN1A ✓
• B KCNQ2
• C CDKL5
• D STXBP1

Explanation

Prolonged hemiclonic febrile seizures beginning before 1 year, evolving into drug-refractory mixed seizures with developmental regression, define Dravet syndrome, caused by loss-of-function mutations in SCN1A encoding neuronal voltage-gated sodium channels. This explains why sodium channel blockers such as carbamazepine and phenytoin aggravate seizures, a hallmark clue that excludes KCNQ2 and other epileptic encephalopathy genes here.

Reference: Swaiman Pediatric Neurology, 6th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.