Test Catalog

Test ID: FSCA3    
SCA3 (MJC/ATXN3) Repeat Expansion

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Hereditary ataxias are a group of heterogeneous neurological disorders predominantly characterized by balance issues, progressive incoordination of gait and limbs, speech and eye movements (2, 3). Additional neurologic and systemic symptoms may be present based on the particular subtype (3). The overall prevalence of hereditary ataxias varies depending on the population but is estimated to be 1-9:100,000 (3).


Hereditary ataxias may be broken down into subtypes based on the mode in inheritance. Autosomal dominant ataxias are a clinically diverse group of disorders that consist of spinocerebellar ataxias (SCAs), episodic ataxias (EA), and some complex forms of ataxia (3). Autosomal recessive ataxias are also clinically heterogeneous but typically characterized by areflexia, peripheral sensorimotor neuropathy (often with loss of the sense of proprioception and vibration) and non-neurologic symptoms (2, 3).


Repeat expansions of CAG in the ATXN3 gene have been associated with spinocerebellar ataxia-3 (SCA3), also known as Machado Joseph disease (MJD). This disorder is characterized by eye lid retraction and infrequent blinking leading to a “staring eyes” phenotype, ophthalmoparesis, and impaired speech and swallowing (4).  Other associated features including peripheral neuropathy, dystonia, and distal amyotrophy with areflexia may be present to varying degrees depending on the size of the repeat length (larger repeats being associated with more severe phenotypes) (4, 5). Age of onset follows an inverse relationship with the number of CAG repeats in the abnormal allele (4). Cases of SCA3 may exhibit anticipation from one generation to the next (4).

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

SCA3 CAG Repeat Ranges:

Normal: < = 44

Borderline 45 - 59

Positive > = 60

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Durr, A. (2010) Lancet Neurol 9: 885-94. (PMID: 20723845)

2. Fogel, BL, et al. (2007) Lancet Neurol 6: 245-57. (PMID: 17303531)

3. Sandford, E, et al. (2014) Genes (Basel) 5: 586-603. (PMID: 25055202)

4. Paulson, HL. (2009) J Neuroophthalmol 29: 227-37. (PMID: 19726947)

5. Franca, MC, et al. (2008) Arch Neurol 65: 525-9. (PMID: 18413477)