Supplementary Material for: External laryngeal tremor in adult-onset Alexander disease

Introduction. Alexander disease is caused by mutations in GFAP, the glial fibrillary acidic protein gene. External laryngeal tremor has not been reported in adult-onset Alexander disease (AOAxD). The aims of this work were to report one such case, and to review the literature on palatolaryngeal tremor and AOAxD.
Case presentation. A 43-year-old man experienced involuntary movements at the front of his neck. Continuous, rhythmic vertical movements of the laryngeal skeleton, soft palate and tongue, and lower-limb dysmetria, were observed. The pathogenic GFAP variant, c.994G>A; p.(Glu332Lys) was found. MRI demonstrated spinal cord and medulla oblongata atrophy, and hyperintensities at the cerebellum and cerebral white matter.
Conclusion. External laryngeal and palatopharyngeal tremor, and cerebellar ataxia, constituted a mild phenotype as expected from this variant, herein reported in isolation for the third time. Imaging was consistent with AOAxD, including the so-called tadpole sign. Additional studies are necessary to define this infrequent disease.

引言
亚历山大病由胶质纤维酸性蛋白（glial fibrillary acidic protein, GFAP）基因的突变引发。目前尚未见成人起病型亚历山大病（adult-onset Alexander disease, AOAxD）合并喉外震颤的相关报道。本研究旨在报道1例此类病例，并复习关于腭喉震颤与AOAxD的相关文献。

病例报告
一名43岁男性出现颈前部不自主运动。查体可见喉骨架、软腭及舌持续性节律性垂直运动，伴下肢辨距不良。检测到致病性GFAP变异：c.994G>A；p.(Glu332Lys)。磁共振成像（magnetic resonance imaging, MRI）显示脊髓及延髓萎缩，小脑与大脑白质存在高信号影。

结论
该致病性变异对应的表型较为轻微，表现为喉外震颤、腭咽震颤及小脑共济失调，本次为第3例单独报道此类病例。影像学表现符合AOAxD特征，包括典型的“蝌蚪征”。仍需开展进一步研究以明确这一罕见疾病。