Study Updates

ERGENT’s motivating hypothesis is that there are specific criteria that if broadly applied, would identify patients with a high likelihood of having epilepsy caused by changes in single genes. As an example of how these criteria are applied, this ERGENT Dispatch reviews how the first study application received was considered.

A newborn began having seizures on the first day of life; EEG revealed a burst-suppression pattern. Although the onset age and EEG pattern are very important indicators of possible genetic epilepsy, additional information provided in the brief application suggested a potential alternative diagnosis. The APGAR screening test scores were low; blood testing showed severe hyponatremia (low sodium). Other tests also returned outside the normal limits including serum ammonia and creatinine, and the brain MR scan was interpreted as hypoxia-ischemia.

We know that inborn errors that disrupt energy metabolism can mimic hypoxia-ischemia. Indeed, the lack of physiologic indicators (e.g. acidosis, identified major perinatal event) prompted the treating providers to perform tests screening for inborn errors of metabolism including serum lactate, pyruvate, plasma amino acids, free and total carnitine, acylcarnitine, and urine organic acids--those test results were pending (not yet available) at the time of application.

This neonate was not eligible for ERGENT. The application data suggested that seizures were most likely provoked by hypoxia-ischemia and/or metabolic abnormalities. Neonatal-onset genetic epilepsy, most commonly caused by variants in the KCNQ2 and SCN2A genes, typically presents in the first days or weeks of life with focal tonic seizures refractory to anticonvulsants and an abnormal EEG background with multifocal epileptiform discharges and discontinuity. The EEG may have segments with a burst-suppression pattern. MR changes or abnormal findings in serum, urine, and/or cerebrospinal fluid that suggest other alternative causes, make epilepsy due to variants in single genes less likely. More extensive evaluation (including, in this patient, metabolic abnormality screening) might lead to new alternatives, and might even lead the caregivers to again consider other genetic tests.

Posted 12/17/2018 by the ERGENT co-investigators.