Clinical characteristics: Spinal and bulbar muscular atrophy (SBMA) is a gradually progressive neuromuscular disorder in which degeneration of lower motor neurons results in muscle weakness, muscle atrophy, and fasciculations in affected males. Affected individuals often show gynecomastia, testicular atrophy, and reduced fertility as a result of mild androgen insensitivity.
Diagnosis/testing: The diagnosis of SBMA is established in a male proband by the identification of a hemizygous expansion of a CAG trinucleotide repeat (>35 CAGs) in AR by molecular genetic testing.
Management: Treatment of manifestations: Use of braces and walkers for ambulation as needed as the disease progresses; standard treatments for dysarthria and dysphagia; breast reduction surgery for gynecomastia as needed; standard treatment per cardiologist and/or endocrinologist for cardiac manifestations and metabolic syndrome; psychosocial support and education to decrease stress and burden on caregivers.
Surveillance: Annual assessment of strength, mobility, activities of daily living, speech, and feeding issues; annual assessment of pulmonary function in those with advanced disease; annual assessment of cholesterol and triglycerides, with hepatic function testing if elevated; annual assessment of cardiovascular health per cardiologist; assessment of need for family and caregiver support.
Other: Clinical trials of anti-androgen drugs (e.g., leuprorelin) did not consistently reveal significant efficacy, but leuprorelin was efficacious as a treatment for dysphagia in a follow-up clinical trial in Japan, leading to its approval in Japan but not elsewhere. Based on animal studies, administration of testosterone and its analogs may worsen motor neuron disease.
Genetic counseling: SBMA is inherited in an X-linked manner. Affected males who are fertile pass the expanded CAG repeat to each daughter. Carrier females have a 50% chance of transmitting the CAG trinucleotide expansion to each child; males who inherit it will be affected; females who inherit it will be carriers and will usually not be affected. Carrier testing for at-risk female relatives and prenatal testing for a pregnancy at increased risk are possible if the expanded CAG repeat has been identified in an affected family member.
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