Spinal and bulbar muscular atrophy

Spinal and bulbar muscular atrophy is a disorder of specialized nerve cells that control muscle movement (motor neurons). This condition, which mainly affects males, is characterized by muscle weakness and wasting (atrophy) that usually begins in adulthood and worsens slowly over time. Muscle wasting in the arms and legs results in cramping, difficulty walking, and a tendency to fall. Certain muscles in the face and throat (bulbar muscles) are also affected, which causes progressive problems with swallowing and speech. Additionally, muscle twitches (fasciculations) are common. Some men with the disorder experience unusual breast development (gynecomastia) and may be unable to father a child (infertile).

This condition affects fewer than 1 in 50,000 males and is very rare in females.

Mutations in the AR gene cause spinal and bulbar muscular atrophy.

This disorder is caused by a mutation in which a DNA segment, known as a CAG triplet repeat, is abnormally expanded within the androgen receptor (AR) gene. Normally, this DNA segment is repeated up to about 36 times. In people with spinal and bulbar muscular atrophy, the CAG segment is repeated at least 38 times, and may be two or three times its usual length. The abnormally expanded CAG triplet repeat changes the structure of the protein made by the AR gene, disrupting the normal function of motor neurons in the brain and spinal cord. These nerve cells gradually die, leading to the muscle weakness and wasting seen in this condition. People with a higher number of CAG repeats tend to develop signs and symptoms of spinal and bulbar muscular atrophy at an earlier age.

Read more about the AR gene.

This condition is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Some females with one altered copy of the AR gene have mild signs and symptoms related to the condition, including muscle cramps and occasional tremors.