From the Guidelines
Spinal and Bulbar Muscular Atrophy (SBMA) or Kennedy's disease is a genetic disorder characterized by an expansion of CAG repeats.
Key Characteristics
- It is one of the "CAG-repeat disorders" for which direct gene analysis is possible 1
- Also known as Kennedy disease, it is related to other CAG-repeat disorders such as Huntington disease, spinocerebellar ataxia types 1, 2, 3, and 6, and dentatorubropallidoluysian atrophy
- The disorder is caused by an expansion of CAG repeats within a specific gene, leading to neurodegenerative symptoms ### Diagnosis and Testing
- Genetic testing for SBMA/Kennedy disease involves direct analysis of the CAG repeat expansion, similar to testing for other CAG-repeat disorders like Huntington disease 1
- This testing has been available for clinical purposes since the early 1990s, with ongoing advancements in genetic testing technology ### Clinical Context
- SBMA/Kennedy disease is a rare genetic disorder with a distinct clinical presentation, including spinal and bulbar muscular atrophy
- Accurate diagnosis through genetic testing is essential for providing appropriate clinical care and counseling for affected individuals and their families 1
From the Research
Definition and Cause of Spinal and Bulbar Muscular Atrophy (SBMA)
- Spinal and Bulbar Muscular Atrophy (SBMA), also known as Kennedy's disease, is a rare, adult-onset, X-linked recessive neuromuscular disease caused by expansion of a CAG repeat sequence in exon 1 of the androgen receptor gene (AR) encoding a polyglutamine (polyQ) tract 2, 3, 4, 5.
- The polyQ-expanded AR accumulates in nuclei, and initiates degeneration and loss of motor neurons and dorsal root ganglia 2.
Clinical Characteristics
- The disease is characterized by muscle weakness and atrophy localized proximally in the limbs, and bulbar involvement 2, 3, 6.
- Sensory disturbances are associated with the motor phenotype, but may be subclinical 2.
- The most frequent systemic symptom is gynecomastia related to androgen insensitivity, but other abnormalities, such as heart rhythm and urinary disturbances, have also been reported 2.
Diagnosis and Treatment
- The diagnosis of SBMA is based on genetic testing, with 38 CAG repeats taken as pathogenic 2.
- Despite several therapeutic attempts made in mouse models, no effective disease-modifying therapy is yet available, although symptomatic therapy is beneficial for the management of the weakness, fatigue and bulbar symptoms 2, 5.
- Pharmacological inhibition of the toxic accumulation of mutant AR is a potential therapy for SBMA, with leuprorelin showing promise in clinical trials 5.