Abstracts

Rationale:
The SERPINI1 gene on chromosome 3 encodes for a serine protease inhibitor.1  Six missense variants in this gene have been described in the literature to date with a spectrum of phenotypes. SERPINI1 was originally described as the cause of an autosomal dominant disease causing cognitive decline.2 Subsequently, cases of younger patients with progressive myoclonic epilepsy (PME) or electrical status epilepticus of slow wave slep have been described with SERPINI1 pathogenic variants.1,3,4 We present a case of a 30 year old man with progressive myoclonic epilepsy with dementia onset in his early twenties who was found to have a novel missense variant in the SERPINI1 gene.
Method:
The patient is a 30 year old right handed male presenting with symptoms of myoclonic jerks, convulsions, and progressive cognitive decline. Symptoms began at age 15 when he developed myoclonic jerks of the upper extremities. He had a generalized tonic-clonic seizure and was diagnosed with juvenile myoclonic epilepsy (JME). At the age of 23, family started noticing mild cognitive impairment. His cognitive status declined progressively over several years to the point of requiring full time care. He had no family history of epilepsy or cognitive impairment. On examination, he had aphasia, attention impairment and apraxia. Full scale IQ was 53 on neuropsychological testing despite estimated average premorbid function.  He had intention tremor, rare distal myoclonus, and hyperreflexia. Workup revealed 3 Hz generalized spike and wave discharges and a photoparoxysmal response on EEG; MRI brain was normal. FDG PET demonstrated symmetric frontal and parietal hypo metabolism. 
Results:
Following a non-diagnostic epilepsy gene panel, the patient had an exome-based autism/ID panel which revealed a novel variant in SERPINI1 (p.R393P, c.1178 G >C) which was interpreted as likely pathogenic. Parental samples were included for trio analysis which found that this was inherited from his mother who was mosaic for the variant. She is currently asymptomatic.
Conclusion:
This case illustrates the diagnostic importance of genetic testing in patients with epilepsy and neurocognitive decline, and highlights the complexities of counseling in the expanding field of epilepsy genetics. This patient’s mother was unexpectedly found to be mosaic for her son’s variant, with unknown significance for her own prognosis. This case demonstrates the importance of pre-test counseling for family members submitting genetic samples as part of a trio analysis. References •Coutelier, M, Andries, S, Ghariani, B, et al. Neuroserpin mutation causes electrical status epilepticus of slow-wave sleep. Neurology, 71(2008), 64-66. •Davis, RL, Holohan, PD, Shrimpton, AE et al. Familial encephalopathy with neuroserpin inclusion bodies. The American Journal of Pathology, 155(1999), 1901-1913. •Hagen, MC, Murrel, JR, D, M-B, et al. Encephalopathy with neuroserpin inclusion bodies presenting as progressive myoclonus epilepsy and associated with a novel mutation in the proteinase inhibitor 12 gene. Brain Pathology ISSN, 21(2011), 575-582. •Ranza,E, Garcia-Tarado, S. Varvagiannis, K, et al. American Journal of Epilepsy Genetics, 173(2017); 2456-2460.  
Funding:
:N/A