Rinsho Shinkeigaku (Clinical Neurology)

Case Report

A case of generalized dystonia DYT28 with a novel de novo mutation in the KMT2B gene

Kenju Hara, M.D., Ph.D.1j, Haruka Ouchi, M.D.1j, Kohei Hamanaka, M.D., Ph.D.2j, Satoko Miyatake, M.D., Ph.D.2j3j and Naomichi Matsumoto, M.D., Ph.D.2j

1) Department of Neurology, Akita Red Cross Hospital
2) Department of Human Genetics, Yokohama City University Graduate School of Medicine
3) Clinical Genetics Department, Yokohama City University Hospital

The patient exhibited plantarflexion during walking at the age of five. He then developed writer's cramp at the age of six, dysphonia at 15 years, and action-induced dystonia with left knee elevation and trunk swinging when walking at 16 years, which subsequently spread to the right leg at 19 years. Levodopa therapy was ineffective for dystonia. Brain MRI showed no abnormalities. He was diagnosed with DYT28 after detecting a novel heterozygous mutation (c.433C>T, p.Arg145) in the KMT2B gene using whole-exome sequencing at age 39. Furthermore, the patient's parents exhibited normal alleles, confirming the de novo status of KMT2B gene mutation. We should consider DYT28 in addition to DYT1 and DYT5 in patients who developed leg dystonia in childhood.
Supplemental video 1
The patient exhibits a forced and husky voice, which are presumably induced by laryngeal dystonia.
Supplemental video 2
The patient exhibits an abnormal posture, in which he kept his elbows in a high position during the finger-to-nose test. Moreover, he excessively elevates his knee with his foot in the varus position and swings his trunk when walking, indicating action-induced dystonia.
Movie is published with patient's permission.
Full Text of this Article in Japanese PDF (653K)

(CLINICA NEUROL, 62: 856|859, 2022)
key words: generalized dystonia, DYT28, KMT2B, de novo mutation, childhood

(Received: 20-Apr-22)