Abstracts

Rationale: Gene mutations of the voltage and calcium-sensitive potassium channel KCNMA1 gene have been reported to cause both generalized epilepsy and paroxysmal nonkinesigenic dyskinesia. There are only about 20 cases reported in the literature. Here we report a new case with a novel phenotype.Here, we describe a 23 year old female with a previously unreported KCNMA1 mutation with a paroxysmal EEG and with a dystonia like phenotype of spells mimicking epilepsy and remarkably responding to dextroamphetamine. Methods: Retrospective case review of records of MRI,Video EEG studies and Whole Exome Sequencing. Results: Patient was noted since early childhood to have moderate developmental delay: she said her first word and started walking only at about the age of 2 years. At that age she also started experiencing episodes of freezing and staring that would progress to falling to the floor and remaining immobile with limp trunk but markedly tightened grasp, upper extremity stiffening and neck turning. The episodes lasted for 15-­20 seconds each and occurred for up to around 100 times daily. These episodes were thought initially to be epileptic but were not controlled by sequential trials of valproate, ethosuximide, phenobarbital, zonisamide, levetiracetam, temazepam, clonazepam, gabapentin, carbamazepine, or lamotrigine. MRI was negative. Interictal EEG showed diffuse slowing and rare generalized spike slow waves and focal spikes, but Video EEG showed no EEG changes during more than 50 recorded and reviewed spells. Video recordings demonstrated also that the stiffening and turning movements were consistent with dystonia or dystonia like episodes. Extensive metabolic workup was negative. Investigations for narcolepsy/cataplexy were negative. Whole exome sequence analysis demonstrated a heterozygous de novo N536H nonsense mutation in the KCNMA1 gene. At age of 8 years the patient was placed on dextroamphetamine for hyperactivity and unexpectedly exhibited a remarkable decrease in spells, from over a 100 per day at that time to none per day or only 5­-10 that occur in the morning before taking medication or when the patient skips a dose. Of note also is that fasting and caffeine drinks were also reported to somewhat decrease spell frequency. Additional trials of memantine and modafinil and ketogenic diet did not help.  Currently at age of 23 she continues to have, without fail, this remarkable and consistent response to dextroamphetamine XR and has flurries of disabling spells any time she delays or skips a dose. On exam, patient has moderate to severe cognitive delay, diffuse mildly decreased tone, scoliosis, and a shuffling crouched gait. Conclusions: Our patient demonstrates a novel KCNMA1 mutation and phenotype which appears to represent very unusual dystonia like spells that were surprisingly controlled with dextroamphetamine. Funding: None