Reviewing the Clinical Spectrum Related to KMT2B Gene Mutations: an Unusual Clinical Presentation and a Possible New Pathogenic Mutation: a Case Report

KMT2B-related dystonia is a generalized childhood-onset dystonia. Since its first description in 2016, different phenotypic spectra have been described. The aim of this case report is to provide data that may help to understand the spectrum of disorders related to KMT2B gene mutations. We present two members of a family with a previously undescribed possible pathogenic mutation as well as an unusual presentation of dystonia associated with KMT2B gene mutations: a focal dystonia and an adult-onset dystonia. The index patient is a 32-year-old woman with generalized dystonia. Her maternal uncle presented focal dystonia. Next-generation sequencing revealed a heterozygous nonsense mutation in the KMT2B gene (19q13.12), described as a variant of uncertain significance (VUS). Although the characteristic phenotype of KMT2B dystonia is a generalized childhood-onset dystonia, different phenotypes are described depending on the type of mutation of this gene, varying also the age of symptom onset and the penetrance of the mutation. Asymptomatic or subclinical carriers and adult-onset dystonia have been described. Due to the low prevalence of this variant in the general population and the low penetrance and high intrafamilial variability of this entity, we suggest that this mutation could be a pathogenic variant. Dystonia related to the KMT2B gene is an emerging and prevalent monogenic dystonia whose incidence, genetic variability, and clinical spectrum remain unknown. Although the study of this gene is indicated in childhood-onset dystonia, the description of cases such as ours shows that its sequencing in patients with a family history and with a dystonia of other characteristics may be useful to achieve a better understanding of this entity.