FHF1 (FGF12) epileptic encephalopathy

Neurol Genet. 2016 Oct 28;2(6):e115. doi: 10.1212/NXG.0000000000000115. eCollection 2016 Dec.


Voltage-gated sodium channels (Navs) are mainstays of neuronal function, and mutations in the genes encoding CNS Navs (Nav1.1 [SCN1A], Nav1.2 [SCN2A], Nav1.3 [SCN3A], and Nav1.6 [SCN8A]) are causes of some of the most common and severe genetic epilepsies and epileptic encephalopathies (EE).1 Fibroblast-growth-factor homologous factors (FHFs) compose a family of 4 proteins that interact with the C-terminal tails of Navs to modulate the channels' fast, and long-term, inactivations.2FHF2 mutation is a rare cause of generalized epilepsy with febrile seizures plus (GEFS+).3 Recently, a de novo FHF1 mutation (p.R52H) was reported in early-onset EE in 2 siblings.4 We report 3 patients from unrelated families with the same FHF1 p.R52H mutation. The 5 cases together frame the FHF1 R52H EE from infancy to adulthood. As discussed below, this gain-of-function disease may be amenable to personalized therapy.