The Neurodevelopmental and Motor Phenotype of SCA21 (ATX-TMEM240).
The Neurodevelopmental and Motor Phenotype of SCA21 (ATX-TMEM240).
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DOI：
10.1177/0883073820943488
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发表时间：
2020-12
影响因子：
1.9
通讯作者：
Wilson RB
中科院分区：
文献类型：
--
作者：
Burdekin ED;Fogel BL;Jeste SS;Martinez J;Rexach JE;DiStefano C;Hyde C;Safari T;Wilson RB
脊髓小脑性共济失调21型（SCA 21/ATX-TMEM 240）是一种罕见的小脑性共济失调，通常表现为运动、认知和行为障碍。尽管这些特征已被确定为SCA 21临床表现的一部分，但与SCA 21相关的神经发育障碍尚未得到很好的研究或描述。在这里，我们提出了广泛的表型数据，从一个SCA 21家庭在美国的三个主题。基因检测表明c.196 G>A（p.Gly66Arg）变异是与该疾病相关的第二个复发性突变。标准化发育评估显示，认知、适应功能、运动技能和社会沟通方面存在显著缺陷，其中两名受试者被诊断为自闭症谱系障碍，这在SCA 21中从未描述过。定量步态分析显示明显异常的时空步态变量指示不良的步态控制和小脑以及非小脑功能障碍。临床评价还强调了临床症状的显著变化，共济失调程度越高，神经发育障碍诊断的严重程度越高。值得注意的是，随着时间的推移，神经发育结果随着干预而改善。总之，该病例系列确定神经发育障碍的表现是SCA 21的关键特征，可能先于运动异常的存在。此外，共济失调和神经发育障碍在这些科目的共存表明脊髓小脑通路在这两个结果的作用。这项研究的结果强调了在进行性运动异常的背景下评估神经发育问题的重要性，以及及时干预以最终改善SCA 21患者生活质量的必要性。
Spinocerebellar ataxia type 21 (SCA21/ATX-TMEM240) is a rare form of cerebellar ataxia that commonly presents with motor, cognitive, and behavioral impairments. Although these features have been identified as part of the clinical manifestations of SCA21, the neurodevelopmental disorders associated with SCA21 have not been well studied or described. Here we present extensive phenotypic data for three subjects from a SCA21 family in the United States. Genetic testing demonstrated the c.196 G>A (p.Gly66Arg) variant to be a second recurrent mutation associated with the disorder. Standardized developmental assessment revealed significant deficits in cognition, adaptive function, motor skills, and social communication with two of the subjects having diagnoses of Autism Spectrum Disorder, which has never been described in SCA21. Quantitative gait analysis showed markedly abnormal spatiotemporal gait variables indicative of poor gait control and cerebellar as well as non-cerebellar dysfunction. Clinical evaluation also highlighted a striking variability in clinical symptoms, with greater ataxia correlating with greater severity of neurodevelopmental disorder diagnoses. Notably, neurodevelopmental outcomes have improved with intervention over time. Taken together, this case series identifies that the manifestation of neurodevelopmental disorders is a key feature of SCA21 and may precede the presence of motor abnormalities. Furthermore, the coexistence of ataxia and neurodevelopmental disorders in these subjects suggests a role for spinocerebellar pathways in both outcomes. The findings in this study highlight the importance of evaluation of neurodevelopmental concerns in the context of progressive motor abnormalities and the need for timely intervention to ultimately improve quality of life for individuals with SCA21.
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影响因子：
9.9
作者：
Beauchet, O.;Annweiler, C.;Allali, G.
通讯作者：
Allali, G.
DOI：
10.1044/2019_jslhr-s-18-0380
发表时间：
2019-09-01
影响因子：
2.6
作者：
Iuzzini-Seigel, Jenya
通讯作者：
Iuzzini-Seigel, Jenya
影响因子：
9.8
作者：
Sato, Nozomu;Amino, Takeshi;Mizusawa, Hidehiro
通讯作者：
Mizusawa, Hidehiro
影响因子：
38.1
作者：
Nonnekes, Jorik;Goselink, Rianne J. M.;Bloem, Bastiaan R.
通讯作者：
Bloem, Bastiaan R.
DOI：
10.1097/wno0b013e3181b416de
发表时间：
2009-09
期刊：
Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society
影响因子：
--
作者：
Paulson HL
通讯作者：
Paulson HL