New evidence supports RYR3 as a candidate gene for developmental and epileptic encephalopathy

The present case of DEE caused by a <i>RYR3</i> heterozygous variant is consistent with previous rare cases of epilepsy caused by <i>RYR3</i> gene variants in terms of pathogenesis and clinical features, but significantly different from congenital myopathy type 20. Our findings provide important evidence for the diagnosis of <i>RYR3</i>-related DEE, and we hypothesize that RYR3 gain-of-function variants resulting in "leaky" Ca²⁺ release channels may be a molecular genetic feature leading to DEE rather than myopathy.