Trigeminal neuralgia and genetics: A systematic review

Abstract

Trigeminal neuralgia (TN) is a severe facial pain disease of unknown cause and unclear genetic background. To examine the existing knowledge about genetics in TN, we performed a systematic study asking about the prevalence of familial trigeminal neuralgia, and which genes that have been identified in human TN studies and in animal models of trigeminal pain. MedLine, Embase, Cochrane Library and Web of Science were searched from inception to January 2021. 71 studies were included in the systematic review. Currently, few studies provide information about the prevalence of familial TN; the available evidence indicates that about 1–2% of TN cases have the familial form. The available human studies propose the following genes to be possible contributors to development of TN: CACNA1A, CACNA1H, CACNA1F, KCNK1, TRAK1, SCN9A, SCN8A, SCN3A, SCN10A, SCN5A, NTRK1, GABRG1, MPZ gene, MAOA gene and SLC6A4. Their role in familial TN still needs to be addressed. The experimental animal studies suggest an emerging role of genetics in trigeminal pain, though the animal models may be more relevant for trigeminal neuropathic pain than TN per se. In summary, this systematic review suggests a more important role of genetic factors in TN pathogenesis than previously assumed.

Familial occurrence of classical and idiopathic trigeminal neuralgia

“…Until recently, limited attention has been given to genetic factors in TN, reflect by the small number of genetic studies about TN [4]. Likewise, a recent systematic review identified in the literature from 1938 to 2019, 27 families with 98 TN individuals and a reported prevalence of familial TN about 1-2% [5]. In contrast to these previous figures, Di Stefano [15] recently referred to a material of 88 TN patients wherein seven patients with classical TN and four cases with idiopathic TN reported other familial members with TN.…”

“…From the existing literature, there is an increasing number of possible candidate genes in TN [5][6][7]. In particular, mutation in genes coding for voltage-gated ion channels (sodium, calcium, potassium and chloride) and TRP channels may alter neuronal excitability that increase susceptibility for developing TN [15,42,[45][46][47].…”

“…While genetic studies in TN have been scarce [4], several recent reviews point to a possibly important role of genetic factors in TN pathogenesis [5][6][7]. In particular, genes coding for voltage-gated ion channels such as sodium, calcium, potassium and chloride channels are important candidate genes in human studies [5].…”

“…Since long, it has been known that a familial form of TN exists [8][9][10]. A recent systematic review [5] referred to 27 families and 98 TN patients with familial TN reported in the literature between 1938 and 2019, and a prevalence of familial TN among patients with diagnosed TN about 1-2% [8,[11][12][13][14]. These figures may represent underreporting as Di Steffano et al [15] within a cohort of 88 TN patients identified familial TN in seven patients with classical TN and four patients with idiopathic TN.…”

Trigeminal Neuralgia As the Principal Manifestation of Anaplasmosis: A Case Report

“…Once these causes are ruled out, many cases are considered idiopathic (Figure 3). Additionally, there is a likely genetic transmission of a predisposition for trigeminal neuralgia via mechanisms such as abnormalities of sodium channels or dysfunction of nociceptors that lead to sensitization [18]. Lyme disease can present with symptoms of meningitis such as neck stiffness, headache, and facial palsy [3].…”