LB: Kennedy’s Disease/SBMA: Clinical Review



Poster Number: T440


Anastasia Gromova, PhD, UC Irvine

Kennedy’s Disease (KD), also known as Spinal and Bulbar Muscular Atrophy (SBMA), is a rare, X-linked neuromuscular disease caused by a polyglutamine expansion mutation in the Androgen Receptor (AR) gene. Patients with KD present with a progressive muscle weakness accompanied by fasciculations and cramping, typically in the third or fourth decade of life. KD classically starts at the lower proximal limbs and progresses to involve bulbar muscles leading to dysarthria and dysphagia. Due to the requirement of circulating androgens to illicit mutant AR’s pathogenic functions, the disease solely affects men. Currently, there is no approved treatment and clinical interventions are focused on managing symptoms and maintaining mobility. Because standard neuromuscular disease genetic panels do not typically screen for repeat expansions in AR, patients affected by KD are commonly misdiagnosed as Amyotrophic Lateral Sclerosis (ALS). Unlike ALS, KD is generally slowly progressing and not considered fatal, although involvement of the bulbar muscles confers a high risk of choking and aspiration pneumonia. Moreover, due to the pleiotropic functions of AR, KD patients often exhibit a variety of non-neuromuscular symptoms, including metabolic dysfunction, cardiac arrhythmia (Brugada syndrome), sensory neuropathy, and features of androgen insensitivity. Here we present practical diagnostic and treatment information for clinicians about this rare neuromuscular disorder and outline available resources for physicians to improve KD patient quality of life. These efforts are largely driven by the Kennedy’s Disease Association (KDA), a highly involved patient advocacy group that connects patients, caregivers, clinicians, and researchers.