Abstracts

Rationale: Neurite EXtension and MIgration Factor or NEXMIF (formerly KIAA2022) Encephalopathy is a recently described X-linked developmental and epileptic encephalopathy syndrome known to be associated with epilepsy with eyelid myoclonia absences, myoclonic-atonic epilepsy, and more rarely epileptic spasms and Lennox Gastaut syndrome. Developmental regression is also common (Stamberger H., et al. Genetics in Medicine. 2021; 23(2):363-373). Epileptic Encephalopathy with Spike-Wave Activation in Sleep (EE-SWAS) has not previously been reported in association with this genetic syndrome. We describe an individual with a suspected pathogenic NEXMIF variant who developed EE-SWAS and responded to ethosuximide.

Methods: Consent was obtained from the adolescent’s mother for record review. Electronic medical records reviewed spanned a twelve-year period and included electroencephalogram (EEG) reports and tracings, magnetic resonance imaging (MRI) of the brain images, genetic testing results, outpatient and inpatient progress notes, and patient messages and telephone notes.


Results: We describe an adolescent with a suspected pathogenic variant in the NEXMIF gene, as well as history of autism spectrum disorder, developmental delay, eyelid myoclonia without absences, and epilepsy with mixed focal and generalized features, treated with lamotrigine. Family history was notable for a brother with autism spectrum disorder and mother with history of severe childhood developmental delay who both shared the same NEXMIF variant. MRI brain revealed left greater than right periventricular gray matter heterotopia and a left cerebellar developmental venous anomaly. The adolescent was diagnosed with EE-SWAS on overnight EEG performed to evaluate behavioral regression and ongoing eyelid fluttering episodes. EEG was remarkable for a spike wave index in sleep of 100%. EE-SWAS was refractory to high-dose clobazam. Steroids were offered but deferred due to parental concerns regarding side effects. EE-SWAS resolved within approximately 2 months following uptitration of ethosuximide to a moderate weight-based dose, with reduction in spike wave index and with improvement in behavioral and developmental regression. Overnight EEG normalized after 4 months of ethosuximide therapy.

Conclusions: Several distinct epilepsy syndromes have previously been associated with NEXMIF encephalopathy. We present a novel case of NEXMIF encephalopathy with EE-SWAS. While further studies are needed, clinicians should have a low threshold to screen individuals with known NEXMIF encephalopathy and developmental regression for EE-SWAS and consider trial of ethosuximide if traditional EE-SWAS medications are not effective.

Funding: None