Abstracts

Rationale: We present a case of heterozygous genetic mutation in the SUOX gene with variant c.514A >G (p.Thr172Ala) which has not yet been correlated with Doose syndrome, which is a myoclonic-atonic seizure disorder most prominent in the pediatric population. Approximately 35-40% of first-degree relatives of patients also develop clinical seizures. Several common genetic mutations have already been delineated in the literature including SCN1A, SCN1B, SCL2A1, SLC6A1, GABRG2 as well as some rarer mutations like KCNA2, GABRB3, and CHD2.

Methods: Case Report

Results: Patient is a developmentally normal 7-year-old female with prior history of ADHD and a family history of SUDEP (paternal grandfather) who started seizures at age 5 years. Her initial seizures involved staring and a subsequent fall to the ground. She was initially placed on ethosuximide with concern for absence seizures. A month later, she started with a new seizure described as “drop attacks,” identified by suddenly falling forward to the ground, which were labelled as myoclonic-astatic seizures. She also had intermittent generalized tonic clonic seizures. EEG results showed interictal generalized polyspikes, paroxysmal fast & ictal generalized polyspike and wave with evolution (Fig 1). Her MRI brain was normal except for an incidental left choroidal fissure cyst (Fig 2). Patient’s dialeptic and generalized tonic-clonic seizures improved on anti-epileptic medications. Levetiracetam, topiramate, and valproic acid showed partial response and were not tolerated due to side effects. Lamotrigine and perampanel made drop attacks worse and zonisamide was ineffective. The drop attacks also showed partial response to clobazam (40 mg/d), phenobarbital (97.5 mg/d), and a ketogenic diet. A genetic panel (INVITAE^TM) was performed and a heterozygous mutation in the SUOX gene, variant c.514A >G (p.Thr172Ala), was discovered. To date, the drop attacks have persisted, occurring about 2-5 times per day and each time lasting up to 2 seconds. They have resulted in several facial injuries despite using a helmet.

Conclusions: SUOX is known to code for sulfate oxidase, its deficiency can cause interactable neonatal seizures. Our patient does not present with the classic history, physical, and imaging findings associated with that disorder. Such findings include rapidly progressive encephalopathy, feeding difficulties, progressive microcephaly, lens subluxation, and loss of gray-white matter in the cerebral cortex & basal ganglia on MRI imaging. Our patient has SUOX mutation with heterozygous mutation in exon 6, c.514A >G (p.Thr172Ala) which has not previously been correlated with Doose syndrome.

Brain cysts have been previously found to mimic Doose syndrome phenotype, albeit not typically in the temporal lobe as is seen with our patient. Further research is necessary to delineate the possible role of SUOX gene in the pathogenesis of Doose syndrome.

Funding: Please list any funding that was received in support of this abstract.: None.