KMT2B-Related Dystonia in Indian Patients With Literature Review and Emphasis on Asian Cohort

Abstract

ObjectiveaaMutations in the <i>KMT2B</i> gene have been identified in patients previously diagnosed with idiopathic dystonia. Literature on <i>KMT2B</i>-related dystonia is sparse in the Indian and Asian populations.MethodsaaWe report seven patients with <i>KMT2B</i>-related dystonia studied prospectively from May 2021 to September 2022. Patients underwent deep clinical phenotyping and genetic testing by whole-exome sequencing (WES). A systematic literature search was performed to identify the spectrum of previously published <i>KMT2B</i>-related disorders in the Asian subcontinent.ResultsaaThe seven identified patients with <i>KMT2B</i>-related dystonia had a median age at onset of four years. The majority experienced onset in the lower limbs (n = 5, 71.4%), with generalization at a median duration of 2 years. All patients except one had complex phenotypes manifesting as facial dysmorphism (n = 4), microcephaly (n = 3), developmental delay (n = 3), and short stature (n = 1). Magnetic resonance imaging (MRI) abnormalities were present in four cases. WES revealed novel mutations in the <i>KMT2B</i> gene in all patients except one. Compared to the largest cohort of patients with <i>KMT2B</i>-related disorders, the Asian cohort, comprising 42 patients, had a lower prevalence of female patients, facial dysmorphism, microcephaly, intellectual disability, and MRI abnormalities. Protein-truncating variants were more prevalent than missense variants. While microcephaly and short stature were more common in patients with missense mutations, facial dysmorphism was more common in patients with truncating variants. Deep brain stimulation, performed in 17 patients, had satisfactory outcomes.ConclusionaaThis is the largest series of patients with <i>KMT2B</i>-related disorders from India, further expanding the clinico-genotypic spectrum. The extended Asian cohort emphasizes the unique attributes of this part of the world.