Clinical Information

X-linked spinal and bulbar muscular atrophy (spinobulbar muscular atrophy: SBMA; or Kennedy disease) is characterized by onset of progressive muscle weakness, atrophy, and fasciculations typically in the fourth or fifth decade of life. Affected patients also have signs of androgen insensitivity such as gynecomastia, reduced fertility, and testicular atrophy. The clinical severity and age at onset can be quite variable, even within families. Because this is an X-linked disease, males manifest this disorder and females are generally asymptomatic carriers. However, there have been reports of female carriers who exhibit symptoms such as muscle weakness and cramping.

SBMA is caused by an expansion of the CAG trinucleotide repeat in exon 1 of the human androgen receptor (AR) gene. This trinucleotide repeat is polymorphic in the general population, with the number of repeats ranging from 11 to 34. The number of repeats found in affected individuals can range from 38 to 62. There is no consensus as to the clinical significance of alleles of 35 CAG repeats and literature suggests that alleles of 36 to 37 CAG repeats may be associated with reduced penetrance. As with other trinucleotide repeat disorders, anticipation is frequently observed and larger CAG expansions are associated with earlier onset and a more rapid clinical progression.