7型脊髓小脑共济失调

Spinocerebellar Ataxia Type 7

作者信息

La Spada Albert R

机构信息

Distinguished Professor and Vice Chair, Departments of Pathology & Laboratory Medicine and Neurology Director, UCI Institute for Neurotherapeutics University of California Irvine School of Medicine Irvine, California

PMID:20301433

Abstract

CLINICAL CHARACTERISTICS

Spinocerebellar ataxia type 7 (SCA7) comprises a phenotypic spectrum ranging from adolescent- or adult-onset progressive cerebellar ataxia and cone-rod retinal dystrophy to infantile or early-childhood onset with multiorgan failure, an accelerated course, and early death. Anticipation in this nucleotide repeat disorder may be so dramatic that within a family a child with infantile or early-childhood onset may be diagnosed with what is thought to be an unrelated neurodegenerative disorder years before a parent or grandparent with a CAG repeat expansion becomes symptomatic. In adolescent-onset SCA7, the initial manifestation is typically impaired vision, followed by cerebellar ataxia. In those with adult onset, progressive cerebellar ataxia usually precedes the onset of visual manifestations. While the rate of progression varies in these two age groups, the eventual result for almost all affected individuals is loss of vision, severe dysarthria and dysphagia, and a bedridden state with loss of motor control.

DIAGNOSIS/TESTING: The diagnosis of SCA7 is established in a proband by the identification of a heterozygous abnormal CAG trinucleotide repeat expansion in by molecular genetic testing.

MANAGEMENT

Multidisciplinary care involves supportive treatment of: neurologic manifestations – physical and occupational therapy to help maintain mobility and function, and pharmacologic treatment to reduce symptoms; dysarthria – speech and language therapy and alternative communication methods; dysphagia – feeding therapy to improve nutrition and reduce the risk of aspiration; and reduced vision – use of low vision aids and consultation with agencies for the visually impaired. Routine follow up with multidisciplinary care providers. Avoid: alcohol intake (especially if excessive) as it can further impair cerebellar function; foods identified by a registered dietitian as possible causes of dizziness or disorientation. Several ongoing clinical trials for medications used as treatment for ataxia.

GENETIC COUNSELING

SCA7 is inherited in an autosomal dominant manner. Offspring of an affected individual have a 50% chance of inheriting an abnormal CAG repeat expansion in . Once an CAG repeat expansion has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for SCA7 are possible.

摘要

临床特征

7型脊髓小脑共济失调（SCA7）的表型谱范围广泛，从青少年或成人起病的进行性小脑共济失调和视锥视杆细胞视网膜营养不良，到婴儿期或幼儿期起病伴多器官功能衰竭、病程加速及早期死亡。在这种核苷酸重复疾病中，遗传早现现象可能非常显著，以至于在一个家族中，患有婴儿期或幼儿期起病的患儿可能在其携带CAG重复序列扩增的父母或祖父母出现症状前数年，就被诊断为一种被认为是不相关的神经退行性疾病。在青少年起病的SCA7中，最初表现通常是视力受损，随后出现小脑共济失调。在成人起病者中，进行性小脑共济失调通常先于视觉表现出现。虽然这两个年龄组的疾病进展速度有所不同，但几乎所有受影响个体最终的结果都是视力丧失、严重构音障碍和吞咽困难，以及因运动控制丧失而卧床不起。

诊断/检测：通过分子遗传学检测在先证者中鉴定出杂合的异常CAG三核苷酸重复扩增，从而确立SCA7的诊断。

管理

多学科护理包括对以下方面的支持性治疗：神经学表现——物理和职业治疗以帮助维持活动能力和功能，以及药物治疗以减轻症状；构音障碍——言语和语言治疗以及替代交流方法；吞咽困难——喂养治疗以改善营养并降低误吸风险；视力下降——使用低视力辅助器具并咨询视障机构。定期由多学科护理人员进行随访。避免：饮酒（尤其是过量饮酒），因为这会进一步损害小脑功能；避免食用经注册营养师确定可能导致头晕或定向障碍的食物。目前正在进行多项针对共济失调治疗药物的临床试验。