Genetic perspectives on transient global amnesia: A narrative review

Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of anterograde amnesia that can last up to 24 h, in the absence of other neurological symptoms. The pathophysiology of TGA is still unknown and comprehensive studies exploring the genetic basis of TGA are lacking. The primary objective of this review is to examine the incidence and characteristics of familial TGA. A secondary objective is to identify any genes that may be associated with the condition. A literature search of Medline and Embase identified 19 relevant articles, including 6 prospective or retrospective cohort studies, 12 case reports/case series, and one study investigating a single nucleotide polymorphism in TGA patients. Cohort studies included 1648 TGA patients, with 55 familial cases reported, and showed no significant associations. Nevertheless, available data suggest that patients with familial TGA frequently exhibit migraine-related symptoms, with clinical characteristics comparable to those observed in sporadic TGA cases. Case reports and case series described 35 familial cases, further supporting the existence of multiple familial TGA cases -an observation unlikely to be coincidental given the rarity of this condition. Migraine appears to be the most common comorbidity in familial TGA, rather than ischemic risk factors. Finally, a genetic analysis of the Val66Met polymorphism in the brain-derived neurotrophic factor gene, implicated in memory and hippocampal function, was performed in 98 patients and found no association with TGA. In conclusion, although no strong genetic associations have been identified to date, familial clustering suggests a potential heritable component in TGA pathogenesis.