A 7-month-old girl had a prolonged hemiclonic seizure with fever at 5 months, followed by recurrent afebrile and febrile seizures of shifting sides that are refractory to carbamazepine and phenytoin, with slowing of development. Genetic analysis would most likely reveal a mutation in which gene?
- A SCN1A ✓
- B SCN2A
- C KCNQ2
- D CDKL5
Explanation
Dravet syndrome begins in the first year with prolonged hemiclonic febrile seizures that alternate sides, evolve into multiple drug-resistant seizure types, and are accompanied by developmental slowing. More than 80 percent of cases carry a de novo loss-of-function mutation in SCN1A encoding the neuronal voltage-gated sodium channel alpha-1 subunit. Sodium-channel blockers such as carbamazepine and phenytoin characteristically worsen the seizures, as this child's course demonstrates. KCNQ2 causes neonatal-onset familial epilepsy, and CDKL5 causes early-infantile epileptic encephalopathy in girls.
Reference: Swaiman's Pediatric Neurology, 6th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.