Cleary John Douglas, Subramony SH, Ranum Laura PW
Center for NeuroGenetics, Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, Florida
Department of Neurology, University of Florida, Gainesville, Florida
SCA8 is a slowly progressive ataxia with onset typically in the third to fifth decade but with a range from before age one year to after age 60 years. Common initial manifestations are scanning dysarthria with a characteristic drawn-out slowness of speech and gait instability. Over the disease course other findings can include eye movement abnormalities (nystagmus, abnormal pursuit and abnormal saccades, and, rarely, ophthalmoplegia); upper motor neuron involvement; extrapyramidal signs; brain stem signs (dysphagia and poor cough reflex); sensory neuropathy; and cognitive impairment (e.g., executive dysfunction, psychomotor slowing and other features of cerebellar cognitive-affective disorder in some). Life span is typically not shortened.
DIAGNOSIS/TESTING: The diagnosis of SCA8 is established in a proband with suggestive findings and a heterozygous abnormal (CTGCAG) repeat expansion in the two overlapping genes identified by molecular genetic testing.
: Canes and walkers to help prevent falls; modification of the home (e.g., grab bars, raised toilet seats, ramps for motorized chairs) as needed; speech therapy and communication devices for those with dysarthria; weighted eating utensils and dressing hooks to maintain some independence; feeding evaluations to reduce risk of aspiration from dysphagia; physical activity to maintain muscular and cardiopulmonary conditioning. : Routine follow up by the multidisciplinary care team including neurology to assess disease progression; physiatry and occupational and physical therapy to assess mobility and self-help skills; speech and language specialists to assess need for alternative communication method or speech therapy; feeding team to assess nutrition, aspiration risk, and feeding methods; and mental health professionals. : Alcohol can exacerbate incoordination.
SCA8 is inherited in an autosomal dominant manner with reduced penetrance. To date, all individuals diagnosed with SCA8 whose parents have been evaluated with molecular genetic testing have one parent with an (CTGCAG) repeat expansion. The transmitting parent may or may not have clinical manifestations of SCA8. If a parent of the proband is known to have a (CTGCAG) repeat expansion, the risk to each sib of inheriting the repeat expansion is 50%. The (CTGCAG) repeat expansion is highly unstable and almost always changes in size on transmission: the repeat expansion is more likely to become larger when maternally transmitted and more likely to contract with paternal transmission. Sibs who inherit a (CTGCAG) repeat expansion may or may not develop clinical manifestations of SCA8. Once an SCA8 (CTGCAG) repeat expansion has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.
脊髓小脑共济失调8型（SCA8）是一种缓慢进展的共济失调，通常在30至50岁发病，但发病年龄范围从1岁前到60岁后。常见的初始表现为扫描式构音障碍，伴有特征性的语速缓慢和步态不稳。在疾病过程中，其他表现可能包括眼球运动异常（眼球震颤、异常跟踪和异常扫视，很少出现眼肌麻痹）；上运动神经元受累；锥体外系体征；脑干体征（吞咽困难和咳嗽反射减弱）；感觉神经病变；以及认知障碍（例如，执行功能障碍、精神运动迟缓以及部分患者出现的小脑认知情感障碍的其他特征）。通常不缩短寿命。
诊断/检测：通过分子遗传学检测，在具有提示性发现且两个重叠基因中有杂合异常（CTGCAG）重复扩增的先证者中确立SCA8的诊断。
使用手杖和助行器以预防跌倒；根据需要对家庭环境进行改造（例如，安装扶手、抬高马桶座圈、为电动轮椅设置坡道）；为构音障碍患者提供言语治疗和交流设备；使用加重餐具和穿衣挂钩以保持一定的独立性；进行喂养评估以降低吞咽困难导致误吸的风险；进行体育活动以维持肌肉和心肺功能。由多学科护理团队进行常规随访，包括神经内科评估疾病进展；物理医学与康复科以及职业和物理治疗师评估活动能力和自助技能；言语和语言专家评估是否需要替代交流方法或言语治疗；喂养团队评估营养状况、误吸风险和喂养方法；以及心理健康专业人员。酒精会加重共济失调。
SCA8以常染色体显性方式遗传，外显率降低。迄今为止，所有经分子遗传学检测评估其父母的SCA8确诊患者，其父母中有一方存在（CTGCAG）重复扩增。传递基因的父母可能有或没有SCA8的临床表现。如果已知先证者的父母有（CTGCAG）重复扩增，每个同胞继承该重复扩增的风险为50%。（CTGCAG）重复扩增高度不稳定，在传递过程中大小几乎总是发生变化：母系传递时重复扩增更可能变大，父系传递时更可能缩小。继承（CTGCAG）重复扩增的同胞可能有或没有SCA8的临床表现。一旦在受影响的家庭成员中鉴定出SCA8（CTGCAG）重复扩增，对于高风险妊娠可进行产前检测和植入前基因检测。
