Expanding the phenotypic spectrum of FGF12-epilepsy—does prompt precision therapy affect outcomes?

Fibroblast growth factor-12 ( FGF12 ) variants have been associated with developmental and epileptic encephalopathy (DEE) with evidence of modulation of voltage-gated sodium channels Na v 1.2 and Na v 1.6. We aim to expand the phenotypic spectrum of FGF12- related epilepsy with emphasis on precision therapy. We describe 12 patients: eight with neonatal onset seizures with the recurrent p.Arg52His (c.155 G > A) variant, two with a previously unreported p.Glu153Gly (c.458 A > G) variant, one with a p.Gly50Ser (c.148 G > A) variant, and one with a de novo whole-gene duplication. Atypical absence seizures were present in 5/12 patients. Brain MRI was normal in 10/12; one patient’s MRIs showed progressive cerebellar atrophy, and one patient’s MRI showed a hemispheric infarct. 8 patients promptly started on sodium channel blockers became seizure-free with good developmental outcomes while 4 developed DEE. In summary, we expand the phenotypic spectrum of FGF12- related epilepsy and discuss the role of early precision therapy in developmental and epilepsy outcomes.