Abstracts

Rationale: Broaden the epilepsy phenotypes associated with KCNQ2 mutations in infancy.  KCNQ2 mutations are commonly associated with, self-limited familial neonatal epilepsy, KCNQ2 encephalopathy and Myokymia; but to the best of our knowledge, a patient with epilepsy of infancy with migrating focal seizures (EIMFS) and a KCNQ2 mutation has not been reported. Methods: We present an infant with a de novo mutation in the KCNQ2 gene with medically refractory tonic seizures with autonomic features, representing EIMFS on EEG recordings. Results: A male infant was born at 38 weeks gestation via planned caesarean section, with meconium stained liquor requiring PPV and CPAP after a non-complicated pregnancy.  Parents were non-consanguineous and had no family history of seizures or epilepsy.  At 18 hours of life the patient began experiencing seizures characterized by tonic posturing with eye deviation to the right, apnoea and O2 desaturations.  At this time the patient was seen by neurology, with initial exam noting normal bulk and power, hyperreflexia on the left side, with no dysmorphism or neurocutaneous stigmata.  Brain MRI, metabolic (very long chain fatty acids, acylcarnitine, plasma amino acids, and urine sulfites), CSF (Neurotransmitters, glycine and lactate) and infectious workup were unremarkable.  An initial EEG noted reduced background activity in awake state as well as burst suppression during sleep and frequent abnormal waves from both hemispheres.  The patient was trailed on pyridoxine, pyridoxal phosphate, folinic acid, biotin, phenobarbital, midazolam, phenytoin, topiramate and levetiracetam all to little effect, with the seizures increasing in frequency.  The patient was subsequently placed on vEEG and put in a barbiturate-coma for 7 days, with cessation of clinical seizures but the patient still experienced electrographic status epilepticus with seizure discharges noted from both the right and left hemispheres migrating to the opposite hemisphere, suggestive of EIMFS.  A representative seizure starting over left temporal, occipital region and migrating to right temporal central region is shown in Figures A and B.  Ketamine and ketogenic diet were also attempted at this time to little effect.  Goals of care were then discussed with the parents who opted to withdraw treatment.  Supportive management was discontinued, and the patient subsequently decompensated and passed away at the age of 37 days.  A comprehensive epilepsy panel noted a KCNQ2 p. S247L mutation, with no similar mutation found in either parent.   Conclusions: KCNQ2 gene encodes a pore forming subunit of the KCNQ potassium channel.  It is linked to the phenotype of Benign Familial Neonatal seizures, KCNQ2 Encephalopathy and Myokymia.  Our subject has a de novo missense KCNQ2 mutation with EIMFS, which has only been previously described with mutations in the KCNT1 gene.  This case expands potential etiologies of EIMFS, as well as describes a new pathology associated with KCNQ2 mutations. Funding: None.