Spinocerebellar Ataxia Type 6 (SCA6)
Incidence
SCA6 is an autosomal dominant disorder. The overall prevalence of autosomal dominant ataxia is estimated at 1/100,000. The prevalence of SCA6 is calculated to be .02 to .31/100,000. Offspring have a 50% chance of inheriting the gene mutation.
Clinical Characteristics
SCA6 is characterized by adult onset, slowly progressive cerebellar ataxia, dysarthria, and nystagmus.
The phenotypic manifestations of SCA6 are not specific, and thus, the diagnosis of SCA6 rests on molecular genetic testing. Clinical manifestations are fairly uniform. The range in age of onset is between 19 to 71 years. The mean age of onset is between 43 and 52 years. Age of onset and clinical picture vary even within the same family, with siblings having the same mutation differing in age of onset by as much as 12 years or exhibiting, at least initially, an episodic course. Initial symptoms are gait unsteadiness, stumbling, and imbalance in about 90% of cases; the remainder of cases present with dysarthria. Symptoms progress slowly, and eventually all patients have gait ataxia, upper limb incoordination, intention tremor, and dysarthria. Diplopia occurs in about 50% of patients. Others experience visual disturbances related to difficulty fixating on moving objects, as well as horizontal gaze-evoked nystagmus (70-100%) and vertical nystagmus (65-83%). Dysphagia and choking are common. Hyperreflexia and extensor plantar responses occur in up to 40% to 50% of patients. Basal ganglia signs, such as dystonia and blepharospasm, are noted in up to 25% of patients. Mentation is generally preserved, but up to 10% of older patients have dementia. Patients with SCA6 do not have sensory complaints, restless legs, stiffness, migraine, primary visual disturbances, or muscle atrophy. Lifespan is not shortened.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
The diagnosis of SCA6 rests upon the use of DNA-based testing to detect an
abnormal CAG trinucleotide repeat expansion in the CACNA1A gene (chromosomal locus 19p13). Affected individuals have 21 to 33 CAG repeats. Persons with 20 CAG repeats may have episodic ataxia. Such testing detects more than 99% of cases and is widely available. It is necessary to confirm the diagnosis in an affected person using DNA-based testing of the CACNA1A gene to assess the size of the CAG trinucleotide. Prenatal testing by direct DNA-testing is possible for fetuses at 50% risk, but few requests for prenatal testing have been made. The diagnosis of SCA6 rests upon the detection of a CAG trinucleotide repeat expansion in the CACNA1A gene (chromosomal locus 19p13) that is between 21 to 33 cag repeats in a patient with cerebellar ataxia. (The 20-CAG repeat allele may cause episodic ataxia.) This test detects almost 100% of cases of SCA6.