Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 100730, China.
Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China.
Parkinsonism Relat Disord. 2020 Aug;77:76-82. doi: 10.1016/j.parkreldis.2020.06.002. Epub 2020 Jun 9.
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.
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.
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.
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.
KMT2B 相关的肌张力障碍是一种新发现的遗传性肌张力障碍，主要发生在儿童时期。这种肌张力障碍通常进展为全身性肌张力障碍，累及颈部、头部、咽部和喉部。我们的研究总结了中国 KMT2B 相关肌张力障碍患者的基因型-表型特征和深部脑刺激（DBS）疗效。
我们从肌张力障碍样本中通过基因panel 和全外显子测序鉴定了 20 例 KMT2B 变异患者。进一步对这些 KMT2B 突变患者进行了遗传、临床和治疗分析。
我们总结了中国 KMT2B 相关患者的基因型和表型特征，包括 16 例散发性患者和 3 个家系（共 4 例）。35%（7/20）的患者之前已有报道。发病年龄在 1 个月至 24 岁之间（平均 6.90±5.72 岁）。65%（13/20）的患者起病于下肢。上肢或喉部分别占 15%（3/20）和 20%（4/20）的患者。在同一个家庭中，男性患者的症状往往比女性患者更严重。KMT2B 变异的携带者可能表现出没有肌张力障碍的非运动症状。我们的患者还可见异常的内分泌代谢，包括以前从未报道过的骨龄提前。我们的 9 例患者接受了 DBS 手术。DBS 手术后的平均随访时间为 4.9（1.3-16）个月，观察到临床症状明显改善。
中国 KMT2B 相关肌张力障碍患者的基因型和表型谱进一步扩大。到目前为止，DBS 手术可能是严重 KMT2B 相关肌张力障碍患者的首选治疗方法。
