A Systematic Review of the Association between the Age of Onset of Spinal-Bulbar Muscular Atrophy (Kennedy’s Disease) and the Length of CAG Repeats in the Androgen Receptor Gene

Background Spinal bulbar muscular atrophy (SBMA) is an X-linked recessive motor neuron disorder which is caused by the presence of ≥ 38 CAG repeats in the androgen receptor gene. Relatively little is known about SBMA, but existing literature indicates a relationship between CAG repeat number and the onset age of some motor symptoms of SBMA. This literature review explored the effect of larger CAG repeats on the age of weakness onset compared to shorter length CAG repeats in male SBMA patients. Methods Three databases were searched (MEDLINE, SCOPUS, and Web of Science; Oct 2021) along with targeted searches in Cambridge University Press and Annals of Neurology. 514 articles were initially identified, of which 13 were included for qualitative synthesis. Results Eleven of the thirteen articles identified a statistically significant inverse correlation between CAG repeat length and age of weakness onset in SBMA. Five studies indicated that SBMA patients with fewer CAG repeats ( e.g . 35-37) had an older age of weakness onset than patients with a greater number ( e.g . >40) of CAG repeats. The minimum number of CAG repeats associated with weakness was numbered in the mid-to-late thirties. Conclusion Identification of a relationship between CAG repeat number and weakness may enable earlier detection and intervention for SBMA. Limitations of this review include the restriction to English-only studies and differences in statistical methodology used in each study. We recommend that future studies use interviews, chart reviews, and standardized scoring methods to reduce effects of retrospective bias on reporting SBMA signs and symptoms.