Xin-Yao Li1, Li-Fang Dai2, Xin-Hua Wan1, Yi Guo3, Yi Dai1, Shang-Lin Li1, Fang Fang2, Xiao-Hui Wang2, Wei-Hua Zhang2, Ting-Hong Liu4, Zi-Hang Xie4, Tie Fang4, Lin Wang5, Chang-Hong Ding6. 1. Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 100730, China. 2. Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China. 3. Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 100730, China. 4. Department of Functional Neurosurgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China. 5. Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 100730, China. Electronic address: wanglin@pumch.cn. 6. Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China. Electronic address: dingchanghong@bch.com.cn.
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 treatment 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.
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 dystoniapatients in China. METHODS: We identified 20 patients with KMT2B variations from dystonia samples with a gene panel and whole exome sequencing. Genetic, clinical and treatment 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 dystoniapatients were further expanded. DBS surgery might be the preferred option for severe KMT2B-related dystoniapatients till now.
Authors: Maria Abel; Robert Pfister; Iman Hussein; Fahd Alsalloum; Christina Onyinzo; Simon Kappl; Michael Zech; Walter Demmel; Martin Staudt; Manfred Kudernatsch; Steffen Berweck Journal: Front Neurol Date: 2021-05-14 Impact factor: 4.003