Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Spinobulbar Muscular Atrophy (SBMA, Kennedy’s Disease) [M62.59]

OMIM numbers: 313200, 313700 (AR)

Dr. rer. biol. hum. Soheyla Chahrokh-Zadeh

Scientific Background

Spinobulbar muscular atrophy is an X chromosomal recessive neurodegenerative disease. Clinical signs include proximal muscle weakness and atrophy as well as fasciculations mainly affecting the perioral muscles. Other frequent characteristics are intention tremor, muscle spasm, swallowing difficulty, peripheral androgen resistance with restricted fertility and gynecomastia. Usually, signs and symptoms first occur between the 30th and 40th year of life and progress slowly. Due to the X chromosomal inheritance pattern, only men are affected by the disease. Heterozygous women show no signs or symptoms; however, they may pass on the disease.

The disease is caused by degeneration of spinal and bulbar α-motor neurons. The degeneration is caused by a CAG triplet expansion in the translated region of the androgen receptor (AR) gene. While normal persons have 12-35 triplets, affected patients carry 38-53 CAG copies. The result is the integration of a too long sequence of glutamine residues into the androgen receptor protein. As a result, the original structure of the protein changes, and therefore its original function in the spinal and bulbar motor neurons is lost.