Clinical Course of Six Children With GNAO1 Mutations Causing a Severe and Distinctive Movement Disorder
Clinical Course of Six Children With GNAO1 Mutations Causing a Severe and Distinctive Movement Disorder
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DOI：
10.1016/j.pediatrneurol.2016.02.018
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发表时间：
2016-06-01
影响因子：
3.8
通讯作者：
Bernstein, Jonathan A.
中科院分区：
文献类型：
--
作者：
Ananth, Arnitha L.;Robichaux-Viehoever, Amy;Bernstein, Jonathan A.
目的：迄今为止，已在11例患者中描述了GNAO1突变。虽然这些个体大多患有癫痫性脑病，但有4例患者以严重的运动障碍为突出特征。我们描述了在没有癫痫的情况下，有严重舞蹈病、发育迟缓和肌张力低下的GNAO1新发突变患者的最大系列。方法：对来自3家机构的6例GNAO1全外显子组测序检测到的复发性错义突变患者进行分析。我们描述了这些患者的表现、临床过程和对治疗的反应。结果：所有6例患者从婴儿期开始就表现出全面发育迟缓和张力低下。除了一名14岁的患者外，所有患者都在4岁时出现了舞蹈病。神经阻滞剂和丁苯那嗪治疗在舞蹈病的基线治疗中最有效。舞蹈病逐渐进展，6例患者中有4例出现严重、难治性肾小球，需要入住重症监护病房。病情恶化间接导致两名患者死亡。结论：GNAO1突变患者在没有癫痫的情况下可表现为严重的进行性运动障碍。病情恶化可能难以治疗，并可导致危及生命的继发并发症。早期和积极治疗这些恶化，直接进入重症监护病房进行麻醉滴注治疗，可以防止一些继发性并发症。然而，舞蹈病和肾小球可能难以接受最大的药物治疗。
OBJECTIVES: Mutations in GNAO1 have been described in 11 patients to date. Although most of these individuals had epileptic encephalopathy, four patients had a severe movement disorder as the prominent feature. We describe the largest series of patients with de novo GNAO1 mutations who have severe chorea, developmental delay, and hypotonia in the absence of epilepsy. METHODS: Six patients with recurrent missense mutations in GNAO1 as detected by whole exome sequencing were identified at three institutions. We describe the presentation, clinical course, and response to treatment of these patients. RESULTS: All six patients exhibited global developmental delay and hypotonia from infancy. Chorea developed by age four years in all but one patient, who developed chorea at 14 years. Treatments with neuroleptics and tetrabenazine were most effective in the baseline management of chorea. The chorea became gradually progressive and marked by episodes of severe, refractory ballismus requiring intensive care unit admissions in four of six patients. Exacerbations indirectly led to the death of two patients. CONCLUSIONS: Patients with GNAO1 mutations can present with a severe, progressive movement disorder in the absence of epilepsy. Exacerbations may be refractory to treatment and can result in life-threatening secondary complications. Early and aggressive treatment of these exacerbations with direct admission to intensive care units for treatment with anesthetic drips may prevent some secondary complications. However the chorea and ballismus can be refractory to maximum medical therapy.