SYNGAP1 Encephalopathy Presenting with a Phenotype of Epilepsy with Eyelid Myoclonia (Jeavons Syndrome)

A 10-year-old girl was evaluated for developmental delay and constipation at age 15 months and was subsequently diagnosed with intellectual disability and autism spectrum disorder at 2 years. There was no family history of epilepsy or cognitive impairment. She had significant self-injurious behavior and aggression. Magnetic resonance imaging at age 18 months was normal.

At age of 4 years, she had seizure onset with multiple daily episodes of staring and eye flutter. Electroencephalogram (EEG) showed eye closure induced generalized spike and wave discharges with associated eyelid myoclonia ([Video 1]), absence seizures, and photoparoxysmal response, findings suggestive of Epilepsy with Eyelid Myoclonia (EEM).[2] Interictal EEG also showed bi-occipital spikes which could represent fragments of generalized spikes. Antiseizure medications tried included levetiracetam, topiramate, valproic acid, ethosuximide, and cannabidiol. Seizures persisted but there was a reduction of seizures with cannabidiol and ethosuximide. She was treated with clonidine and sertraline for aggression and self-injurious behavior.

Video 1 Video demonstrating eye closure induced eyelid myoclonia. EEG with generalized spike/polyspike-waves with lead in from occipital regions.

Gene panel testing was performed at age 6 years to evaluate for etiology of cognitive impairment, autism spectrum disorder, and epilepsy. This was significant for SYNGAP1 mutation [heterozygous, chr6:33410767, c.2438delT(p.l813Rfs*23)] and she was diagnosed with SYNGAP1 encephalopathy.

SYNGAP1 encephalopathy is caused by mutations on chromosome 6p21.32 and may present with the clinical phenotype of epilepsy with myoclonic–atonic seizures (EMAtS), previously known as Doose syndrome or EEM syndrome.[1] [3]

This report highlights that in children with neurodevelopmental delay and epilepsy with phenotype of EEM syndrome, genetic testing for SYNGAP1 mutation should be considered ([Table 1]).

Table 1 Features of EEM and SYNGAP1 encephalopathy

EEM (previously known as Jeavons syndrome)[3]

EEM syndrome phenotype caused by SYNGAP1

mutation[1]

Age at seizure onset

6–8 y

< 3 y

Cognition and neurodevelopment

Normal or borderline intellectual function

Cognitive impairment, behavioral disorders, autism spectrum

Other distinctive seizure types

Absence, generalized tonic-clonic seizures