Publication: Elicited Repetitive Daily Blindness Associated With Gain-of-Function SCN1A Variants and Responsiveness to Sodium Channel Blockers
About
Elicited Repetitive Daily Blindness (ERDB) is a debilitating condition resulting in recurrent, daily episodes of reversible visual loss. ERDB has been described in individuals with Familial Hemiplegic Migraine 3 (FHM3), caused by pathogenic SCN1A variants. Two families with cosegregation of FHM3 and ERDB (families 1-2) have previously been reported associated with SCN1A variants c.4467G > C/p.(Q1489H) and c.4495T > C/p.(F1499L). However, F1499L was also identified in a separate FHM3 family without ERDB. Thus, it is uncertain whether ERDB is a clinical feature in FHM3 besides the 2 identified families. We present 4 new families with cosegregation of FHM3 and ERDB resulting from 3 novel SCN1A variants. The proband in each family was started on sodium channel blocker medication. We performed functional analysis of the previously reported Q1489H and F1499L variants, including the overall effect in GABAergic neurons.
Our study demonstrates that ERDB is a clinical feature in FHM3 patients because of gain-of-function Nav1.1 variants. Patients in this report responded to sodium channel blocker medications.