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Incidence

SCA7 is an autosomal dominant disorder. Offspring of affected individuals have a 50% chance of inheriting the altered gene.

Clinical Characteristics

SCA7 is characterized by progressive cerebellar ataxia, including dysarthria and dysphagia, and retinal dystrophy with progressive central visual loss resulting in blindness in affected adults. Onset in early childhood or infancy has an especially rapid and aggressive course often associated with weight loss and regression of motor milestones. Although formal diagnostic criteria have not been established, SCA7 can be diagnosed with confidence in adults who have the following findings: Progressive incoordination due to cerebellar ataxia, including dysarthria/dysphagia, dysmetria, and dysdiadochokinesia. Visual problems, retinal degeneration with abnormalities of rod and cone function on electroretinogram (ERG) testing, and a tritan-axis (blue/yellow) defect on detailed color vision testing, and (late in the course of the disease) macular changes on fundoscopic examination. In children, symptoms are similar; however, the progression of the disease is often more rapid and aggressive than in adults. Diagnosis may be difficult in infancy when ataxia and visual loss are not obvious. (Failure to thrive and loss of motor milestones may be the earliest clues.). SCA7 in adults is characterized by abnormalities in color vision and central visual acuity, which often present as the initial signs in the late teens or early 20's before the onset of cerebellar findings. Progressive cerebellar ataxia with classic findings of dysmetria, dysdiadochokinesia, and poor coordination may precede, but usually follow, the onset of visual symptoms. The retinal degeneration is progressive, resulting in blindness. The cerebellar ataxia progresses to severe dysarthria, dysphagia, and loss of motor control. The age of onset ranges from infancy with an accelerated course and early death to the fifth or (more rarely) the sixth decade with a slower progression. The earlier initial symptoms manifest themselves, the more rapidly progressive retinal degeneration occurs. For example, in children showing initial symptoms at or before adolescence, blindness can occur within a few years. Individuals showing symptoms in their teens may be blind within a decade or less. Later onset corresponds with slower course. In infantile onset, the cerebellar and brainstem degeneration is so rapid that retinal degeneration may not have time to clearly present; visual loss may not be evident. In children, the combination of retinal disease and ataxia may be confused with lipid storage diseases and ceroid lipofucsinoses. Cerebellar findings. In adults, ocular saccades may become markedly slowed. The cerebellar signs and symptoms progress in a similar fashion, leading to a bedridden state. Hyperreflexivity develops along with spasticity as the disease progresses. The rate of progression in affected individuals may be quite variable. In children, symptoms are similar, but the course is markedly more rapid. In infancy or early childhood, ataxia may not be obvious, but muscle wasting, weakness, and hypotonia are common. Although many of the clinical and pathological findings of the other SCAs overlap with SCA7, the retinal degenerative component is the distinguishing feature of this hereditary ataxia.

Precipitants

no

Provocation Tests

no

Diagnostic Procedures

The diagnosis of SCA7 can be made clinically in adults with retinal and cerebellar signs and an autosomal dominant family history. Detection of a CAG trinucleotide repeat expansion in the SCA7 gene (chromosomal locus 3p21-p12) greater than 37 CAG repeats can be used to confirm the diagnosis in symptomatic adults and establish the diagnosis in atypical cases, particularly in children. As persons with ataxia may have visual loss for many reasons (such as diabetic retinopathy, multiple sclerosis, or age-related macular degeneration), such molecular testing is an important part of the diagnostic evaluation of ataxia. Equivocal findings in adults and suggestive findings in a child are also indications for molecular testing. Although the diagnosis of SCA7 can be made clinically, DNA-based testing to detect an abnormal CAG trinucleotide repeat expansion in the SCA7 gene on chromosome 3p21-p12 is invaluable for eventual diagnosis. Affected individuals usually have more than 37 CAG repeats on the mutated allele, although individuals with fewer repeats may also present with symptoms. Molecular testing is specific, nearly 100% sensitive, and widely available. It is necessary to confirm the diagnosis in an affected family member using DNA-based testing of the SCA7 gene. Prenatal testing by direct DNA testing is possible for fetuses at 50% risk. Although many of the clinical and pathological findings of the other SCAs overlap with SCA7, the retinal degenerative component is the distinguishing feature of this hereditary ataxia.