Spinocerebellar Ataxia Type 2 (SCA2)
Incidence
SCA2 is an autosomal dominant disorder. It is necessary to confirm the diagnosis in an affected person using DNA-based testing of the SCA2 gene.
Clinical Characteristics
SCA2 is characterized by progressive cerebellar ataxia, including nystagmus, slow saccadic eye movements and, in some patients, ophthalmoparesis. Pyramidal findings are present; deep tendon reflexes are brisk early on and are absent later in the course. The diagnosis of SCA2 rests upon the detection of a CAG trinucleotide repeat expansion in the SCA2 gene (chromosomal locus 12q24) in a patient with cerebellar ataxia. Such testing detects 100% of cases. The diagnosis of SCA2 is suspected in patients with slowly progressive ataxia associated with the ocular findings of nystagmus, slow saccadic eye movements, and in some patients, ophthalmoparesis. No clinical features of SCA2 exist that allow diagnosis with certainty; thus, diagnosis depends on molecular genetic testing. Clinical Description: Mean age of onset is typically in the 4th decade with a 10-15 year disease duration. The disease is more rapidly progressive with onset before age 20. In the original Cuban study, earliest symptoms included gait ataxia often accompanied by leg cramps. Greater than 50% of patients developed a kinetic or postural tremor, decreased muscle tone and tendon reflexes, and abnormal eye movements with slowed saccades progressing to supranuclear ophthalmoplegia. Belal et al (1994) described a surprising 23% incidence of fasiculations, dystonia, and/or chorea (9%-38%), and dementia (~1/3 of patients) in the family he studied. Durr et al (1995) emphasized the prevalence of dementia in SCA2 in that 29% of their patients showed an abnormal mental status. Using direct analysis of the SCA2 repeat, Geschwind et al (1997b) found almost universal presence of cerebellar ataxia and slow saccadic eye movements, but also a relatively high incidence of dystonia or chorea (38%) and dementia (37%). Mild, primarily cerebellar symptoms appeared to segregate in some families, whereas others had an early onset with dementia and chorea. Similar findings were also reported by Cancel et al (1997) in a series of 111 patients from 32 families of diverse origins. Slow eye movements were seen in 56%, fasciculations in 25%, and dystonia in 9%. The authors also correlated these findings with disease duration and with increasing CAG repeat length. The size of the CAG trinucleotide repeat of the SCA2 gene can be assayed with molecular genetic testing. This testing detects 100% of cases of SCA2. A polymorphic CAG repeat in the SCA2 gene is unstable and is expanded in all individuals with SCA2. The number of CAG repeats ranges from 14-31 in normal alleles. CAG repeats ranging from 32 to 35 are considered intermediate alleles, because they may or may not be associated with phenotypic changes. Disease-causing alleles range from 36 to 64 CAG repeats. The presence of one disease-causing allele is diagnostic. The test is available clinically.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
No clinical features of SCA2 exist that allow diagnosis with certainty; thus, diagnosis depends on molecular genetic testing. The diagnosis of SCA2 rests upon the use of DNA-based testing to detect an abnormal CAG trinucleotide repeat expansion of the SCA2 gene on chromosome 12q24. Affected individuals have alleles with 36-64 CAG trinucleotide repeats. Such testing detects 100% of cases and is widely available. SCA2 is an autosomal dominant disorder. It is necessary to confirm the diagnosis in an affected person using DNA-based testing of the SCA2 gene to assess the size of the CAG trinucleotide repeat as part of the genetic counseling and testing of asymptomatic family members at risk. Offspring of affected individuals have a 50% chance of inheriting the gene mutation. Prenatal testing by direct DNA testing is possible for fetuses at 50% risk, but few requests have been made for prenatal testing.