Abstract
DEPDC5 is an upstream repressor of the mechanistic target of rapamycin pathway via the GATOR-1
complex. Pathogenic variants causing loss of function typically result in familial
focal epilepsy with variable foci. Neuroimaging may either be normal or show brain
malformations. Lesional and nonlesional cases may be present within the same family.
Here, we describe a parent–child dyad affected by a truncating DEPDC5 pathogenic variant (c.727C > T; p.Arg243*), analyze the epilepsy clinical course,
and describe neuroimaging characteristics from a 3T brain magnetic resonance imaging.
Despite sharing the same variant, patients diverged both in terms of epilepsy severity
and neuroimaging features. Surprisingly, the mother is still suffering from drug-resistant
seizures and has normal neuroimaging, while the child has been experiencing prolonged
seizure freedom notwithstanding a bottom-of-sulcus focal cortical dysplasia. An increasing
gradient of severity has been proposed for families with GATOR1-related epilepsies.
We confirm clinical and neuroradiological expressivities are variable and also suggest
the prognostication of epilepsy outcome may be particularly difficult. The epilepsy
outcome could partially be independent from brain structural abnormalities.
Keywords
mTOR - brain MRI - seizures - focal cortical dysplasia - germinal variants - pathogenic
variants
