Abstracts

Rationale: PKD associated with epilepsy is an uncommon disorder. This condition was initially reported in 2005 when the KCNMA1 gene was identified as pathological and implicated in familial autosomal dominant paroxysmal non-kinesigenic dyskinesia with generalized epilepsy. De novo KCNMA1 gene mutation and resultant PKD with focal or generalized epilepsy is very rare and only few cases have been reported in the literature. Methods: A 3-year-old boy with mild global developmental delays, with no significant family history or parental consanguinity presented at 14 months of age with spells described as behavior arrest lasting for 10-15 seconds. He had other spells during which he leaned forward, raised his eyebrows and grimaced repetitively, occurring 20-30 times daily. These spells did not occur when he was asleep. Initial V-EEG monitoring did not show ictal changes with good PDR during the events indicating that spells were not seizures or narcolepsy. All the spells occurred when he was awake during physical activities. In the interim, MRI brain and electromyography testing were unremarkable. He has been tried on 3 anti-seizure medications, including carbamazepine, levetiracetam, and phenytoin with no significant improvement of his symptoms. He was ultimately diagnosed with PKD based on clinical criteria. Follow up V-EEG monitoring at 24 months showed independent focal epileptiform discharges on the left central and right central/temporal regions with burst of generalized atypical spike waves, with no ictal EEG pattern associated with these spells. Further V-EEG monitoring at 36 months showed multiple absence, atonic, and-myoclonic seizures with evolving generalized atypical spike wave, lasting less than 10 seconds, associated with ictal pattern. Results: Genetic testing was positive for pathogenic variant identified in KCNMA1 gene with heterozygous variant of KCNMA1, Exon 25, c.2984A>G (p.Asn995Ser) which is not present in population data base but observed to be de novo in individuals affected with epilepsy and/or paroxysmal dyskinesia (PMID: 26195193, 29330545, Invitae). In addition, a heterozygousKCNMA1, Exon 1, c.34_36dupAGC (p.Ser12dup) was identified, which was of uncertain significance. Patient was started on valproic acid with modest response and decrease seizure frequency without complete resolution of seizures. Conclusions: The KCNMA1 gene mutation is a rare condition associated with epilepsy and PKD. Our case adds to the limited literature in regards to de novo origin of such condition indicating clinical heterogeneity of disorders caused by KCNMA1 mutations. Treatment of dyskinesia, seizures, or non-epileptic events in these patients is usually difficult and requires trials of multiple anti-seizure medications. Funding: No funding