Clinical phenotypes, genotypes and treatment in Chinese dystonia patients with KMT2B variants

Abstract Background KMT2B-related dystonia is a recently discovered hereditary dystonia that mostly occurs in childhood. This dystonia usually progresses to generalized dystonia with cervical, cranial, pharynx and larynx involvement. Our study summarizes genotype-phenotype features and deep brain stimulation (DBS) efficacy observed with KMT2B-related dystonia patients in China. Methods We identified 20 patients with KMT2B variations from dystonia samples with a gene panel and whole exome sequencing. Genetic, clinical and neuroimaging analyses of these patients with KMT2B mutations were further conducted. Results We summarized the genotype and phenotypic characteristics of KMT2B-related patients in China, including 16 sporadic patients and 3 pedigrees (including 4 patients). Thirty-five percent (7/20) of patients had been published previously. The age of onset was between 1 month and 24 years (average 6.90 ± 5.72 years). Sixty-five percent (13/20) of patients had onset from lower limbs. Upper limbs or larynx accounted for 15% (3/20) and 20% (4/20) of patients, respectively. In the same family, male patients tended to have more severe symptoms than female patients. Carriers of KMT2B variants may present with nonmotor symptoms without dystonia. Abnormal endocrine metabolism could also be seen in our patients, including advanced bone age that had never been reported previously. Nine of our patients underwent DBS surgery. The mean follow-up time was 4.9 (range 1.3–16) months after DBS, and perceptible improvement of clinical symptoms were observed. Conclusions The genotypic and phenotypic spectra of Chinese KMT2B-related dystonia patients were further expanded. DBS surgery might be the preferred option for severe KMT2B-related dystonia patients till now.