August 27, 2015: Spinobulbar muscular atrophy
August 27, 2015
Spinobulbar muscular atrophy
Spinobulbar muscular atrophy (SBMA), also known as Kennedy disease, is a rare motor neuron disease characterized by progressive limb and bulbar weakness. SBMA is caused by a CAG trinucleotide repeat expansion on the X chromosome for the gene encoding the polyglutamine tract in androgen receptors. An accumulation of misfolded polyglutamine proteins in the nuclei of motor neurons has been implicated in the disease pathophysiology.
Weakness typically starts in the legs, then advances to the arms, and contraction fasculations are a common clinical finding. Furthermore, patients experience signs and symptoms of androgen insensitivity, such as gynecomastia and testicular failure. The age of presentation for SBMA is anytime from 14 to 75 years with an average age of onset in the mid-40s; however, age of onset is inversely related to number of CAG repeats. Prognosis is dependent on number of CAG repeats. The disease typically affects men with asymptomatic female carriers. There are currently no disease-modifying therapies available, and treatment is based on symptomatic management.
- Fratta P, Nirmalananthan N, Masset L, et al. Correlation of clinical and molecular features in spinal bulbar muscular atrophy. Neurology 2014; 82: 2077-2084.
- Banno H, Katsuno M, Suzuki K, Tanaka F, Sobue G. Neuropathology and Therapeutic Intervention in Spinal and Bulbar Muscular Atrophy. Int J Mol Sci 2009; 10: 1000–1012.
- Atsuta N, Watanabe H, Ito M, et al. Natural history of spinal and bulbar muscular atrophy (SBMA): a study of 223 Japanese patients. Brain 2006; 129: 1446–1455.
Submitted by Sarah Wesley MD, Department of Neurology, Mount Sinai Beth Israel Medical Center.
Disclosures: Dr. Wesley is a member of the Residents & Fellows Section of Neurology