Authors :
Presenting Author: Madeline Lee, BA – SUNY Upstate Medical Center
Katherine Wojcicki, DO – SUNY Upstate Medical Center
Rationale:
Juvenile Myoclonic Epilepsy (JME) is one of the most common epilepsy syndromes with childhood onset. Currently, genetic testing is not part of the routine clinical evaluation in JME. Recent advances in genetic panels and exome sequencing have made genetic testing widely accessible, however, even in patients with epilepsy syndromes in which genes are not often identified, such as JME. Here, we present an adolescent patient with new-onset epilepsy consistent with JME, who was found to have pseudohypoparathyroidism. Methods:
A single case study is presented to illustrate an example of a genetic endocrine disorder causing medically refractory epilepsy which presented clinically as JME. Results:
A previously healthy, developmentally normal male presented with myoclonic and generalized tonic-clonic (GTC) seizures first noticed at the age of 14 years. His myoclonic seizures were described as morning shoulder/arm jerks. These resolved quickly with Keppra. His GTC seizures were sudden onset without focal features or preceding aura, but persisted monthly until Depakote was also added. Brain MRI was normal. The initial EEG showed 4-6 Hz generalized polyspike and wave discharges (Figure 1). He was diagnosed with JME based on age of onset, seizure semiology, and interictal EEG findings.
Six months later, he developed a new seizure semiology described as his head “feeling like it’s in a simulation” with an accompanying throat tightening sensation, which gave him the urge to drink water excessively. These seizures were captured on EEG and were consistent with absence seizures, characterized by 3-Hz generalized spike/polyspike and wave discharges (Figure 2). Despite trial of high doses of Keppra, Depakote, Zonisamide, and Ethosuximide, he continued to have frequent daily absence seizures, impairing his ability to attend school.
Due to the unusually difficult-to-treat absence seizures with unique semiology, an Invitae epilepsy gene panel was completed, which revealed a pathogenic variant in UPD20 associated with pseudohypoparathyroidism type 1b. Updated labs revealed a newly low calcium (7.5), elevated parathyroid hormone (112), and normal phosphate. Endocrinology diagnosed him with pseudohypoparathyroidism. He was started on Calcitriol and calcium carbonate, resulting in complete seizure freedom while remaining on Keppra and Depakote.
Conclusions:
Though this patient met all clinical and electrographic criteria for a diagnosis of JME, his genetic testing revealed he unexpectedly had pseudohypoparathyroidism, a treatable endocrine disorder. Pseudohypoparathyroidism can present with multiple seizure semiologies and generalized interictal discharges on EEG, similarly to JME, however, it is treated very differently. This case illustrates the value and importance of considering early genetic testing in JME patients, especially if medically intractable. Funding: None