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. 2023 Sep;16(3):285-294.
doi: 10.14802/jmd.23035. Epub 2023 Jun 13.

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

Debjyoti Dhar  1 , Vikram V Holla  1 , Riyanka Kumari  2   3 , Neeharika Sriram  1 , Jitender Saini  4 , Ravi Yadav  1 , Akhilesh Pandey  5   6 , Nitish Kamble  1 , Babylakshmi Muthusamy  2   3 , Pramod Kumar Pal  1
Affiliations

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

Debjyoti Dhar et al. J Mov Disord. 2023 Sep.

Abstract

Objective: aaMutations in the KMT2B gene have been identified in patients previously diagnosed with idiopathic dystonia. Literature on KMT2B-related dystonia is sparse in the Indian and Asian populations.

Methods: aaWe report seven patients with KMT2B-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 KMT2B-related disorders in the Asian subcontinent.

Results: aaThe seven identified patients with KMT2B-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 KMT2B gene in all patients except one. Compared to the largest cohort of patients with KMT2B-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.

Conclusion: aaThis is the largest series of patients with KMT2B-related disorders from India, further expanding the clinico-genotypic spectrum. The extended Asian cohort emphasizes the unique attributes of this part of the world.

Keywords: Asia; Dystonia; Genetics; India; KMT2B.

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Conflict of interest statement

Conflicts of Interest

The authors have no financial conflicts of interest.

Figures

Figure 1.
Figure 1.
Imaging features in patients with KMT2B-related dystonia. Susceptibility-weighted imaging magnetic resonance imaging of the brain of Patient 1 (A), Patient 2 (C), and Patient 4 (E) revealed symmetric hypointensity of the bilateral globus pallidus (GP) with a hypointense lateral streak, whereas the GP was normal in Patient 3 (D) and Patient 6 (G). T2-weighted imaging in Patient 5 (F) and fluid-attenuated inversion recovery imaging in Patient 7 were normal (H). Patient 1 also had scoliosis (B).
Figure 2.
Figure 2.
Geographic distribution of Asian cohort of KMT2B-related disorders. Schematic map of Asia showing the geographic distribution along with the variant details of patients with KMT2B-related disorders reported from Asian subcontinent.
See this image and copyright information in PMC

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