Spinal and bulbar muscular atrophy

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This article is about a type of spinal muscular atrophy linked to a genetic defect in the AR gene. For a list of other conditions with similar names, see Spinal muscular atrophies.
Spinal and bulbar muscular atrophy
Classification and external resources
Specialty neurology
ICD-10 G12.1
ICD-9-CM 335.1
OMIM 313200
DiseasesDB 7144
eMedicine article/1172604
MeSH D055534
Orphanet 481

Spinal and bulbar muscular atrophy (SBMA), also known as spinobulbar muscular atrophy, bulbo-spinal atrophy, X-linked bulbospinal neuropathy (XBSN), X-linked spinal muscular atrophy type 1 (SMAX1), Kennedy's disease (KD), and many other names[1] — is a debilitating neurodegenerative disorder resulting in muscle cramps and progressive weakness due to degeneration of motor neurons in the brain stem and spinal cord.

The condition is associated with mutation of the androgen receptor (AR) gene[2][3][4] and is inherited in an X-linked recessive manner. As with many genetic disorders, no cure is known, although research continues.

Because of its endocrine manifestations related to the impairment of the AR gene, SBMA can be viewed as a variation of the disorders of the androgen insensitivity syndrome (AIS). It is also related to other neurodegenerative diseases caused by similar mutations, such as Huntington's disease and the spinocerebellar ataxias.


SBMA is inherited in an X-linked recessive pattern.

The androgen receptor gene that is mutated in SBMA is located on the X chromosome, and the effects of the mutation may be androgen-dependent, thus only males are fully affected. Females are rarely affected; female carriers tend to have a relatively mild expression of the disease if they show symptoms at all.

Please note that the diagrams will be different if 1) the father is affected AND the mother is unaffected OR 2) if the father is affected and the mother is a carrier.


As reported in 1991, SBMA is caused by expansion of a CAG repeat in the first exon of the androgen receptor gene (trinucleotide repeats).[5] The CAG repeat encodes a polyglutamine tract in the androgen receptor protein. The greater the expansion of the CAG repeat, the earlier the disease onset and more severe the disease manifestations. The repeat expansion likely causes a toxic gain of function in the receptor protein, since loss of receptor function in androgen insensitivity syndrome does not cause motor neuron degeneration. Spinal and bulbar muscular atrophy may share mechanistic features with other disorders that are caused by polyglutamine expansion, such as Huntington's disease. There is currently no treatment or cure for SBMA.

It is a lower motor neuron disease.[6]

Signs and symptoms[edit]

SBMA patients have muscle cramps and progressive weakness due to degeneration of motor neurons in the brain stem and spinal cord.

Ages of onset and severity of manifestations in affected males vary from adolescence to old age, but most commonly develop in middle adult life. The latest onset was described in a male of 84 years of age. KD does not usually compromise longevity. The syndrome has neuromuscular and endocrine manifestations.


Early signs often include weakness of tongue and mouth muscles, fasciculations, and gradually increasing weakness of limb muscles with muscle wasting. In some cases, premature muscle fatigue begins in adolescence. Neuromuscular management is supportive, and the disease progresses very slowly but can eventually lead to extreme disability.


  • Bulbar signs: The bulbar muscles are those supplied by the motor nerves from the brain stem, which control swallowing, breathing, speech, and other functions of the throat. Bulbar signs are problems with these muscles.
  • Lower motor neuron signs: The lower motor neurons are those in the brainstem and spinal cord that directly supply the muscles. Loss of lower motor neurons leads to weakness and wasting of the muscle.
  • Primary sensory neuropathy: Loss of sensation and numbness, usually not noticeable.
  • Intention tremor: Hand tremor with volitional effort.
  • Babinski (plantar) response: When the bottom of the foot is scraped, the toes bend down. An abnormal response would be an upward movement of the toes indicating a problem with higher level (upper) motor neurons.
  • Decreased or absent deep tendon reflexes: When a doctor taps the knee, for example, with a tendon hammer, there is less than normal movement or none at all.


  • Fasciculations: Twitching of muscles when at rest.
  • Cramps: Large muscle spasms.
  • Muscular atrophy: Loss of muscle bulk that occurs when the lower motor neurons do not stimulate the muscle adequately.


  • Gynecomastia: breast enlargement.
  • Impotence
  • Erectile dysfunction
  • Reduced fertility
  • Low sperm count
  • Testicular atrophy: Testicles become smaller and less functional.

Miscellaneous Characteristics:

  • Late onset: Patients usually develop symptoms in the late 30's or afterwards.
  • Symmetry of clinical signs: Muscles are usually affected symmetrically.

Homozygous females[edit]

Homozygous females, both of whose X chromosomes have a mutation leading to CAG expansion of the AR gene, have been reported to show only mild symptoms of muscle cramps and twitching. No endocrinopathy has been described.


This disorder was first described by William R. Kennedy in 1968.[7] In 1991 it was recognized that the AR gene is involved in the disease process. The disease is probably more common than originally thought. A study in Scandinavia suggested a prevalence of 1.3/8,500 making KD the most common form of motor neuron disease in the specific area studied[citation needed]; nobody had been diagnosed before 1995. It has been suggested that some men with SBMA may be misdiagnosed to have amyotrophic lateral sclerosis (ALS).

See also[edit]


  1. ^ Arvin, Shelley (2013-04-01). "Analysis of inconsistencies in terminology of spinal and bulbar muscular atrophy and its effect on retrieval of research". Journal of the Medical Library Association : JMLA 101 (2): 147–150. doi:10.3163/1536-5050.101.2.010. ISSN 1536-5050. PMC 3634378. PMID 23646030. 
  2. ^ Krivickas, L. S. (2003). "Amyotrophic lateral sclerosis and other motor neuron diseases". Physical Medicine and Rehabilitation Clinics of North America 14 (2): 327–345. doi:10.1016/S1047-9651(02)00119-5. PMID 12795519. 
  3. ^ Fischbeck, K. H.; Lieberman, A.; Bailey, C. K.; Abel, A.; Merry, D. E. (1999). "Androgen receptor mutation in Kennedy'sdisease". Philosophical Transactions of the Royal Society B: Biological Sciences 354 (1386): 1075. doi:10.1098/rstb.1999.0461. 
  4. ^ Chen CJ, Fischbeck KH (2006). "Ch. 13: Clinical aspects and the genetic and molecular biology of Kennedy's disease". In Tetsuo Ashizawa; Wells, Robert V. Genetic Instabilities and Neurological Diseases (2nd ed.). Boston: Academic Press. pp. 211–222. ISBN 0-12-369462-0. 
  5. ^ Spada, A. R. L.; Wilson, E. M.; Lubahn, D. B.; Harding, A. E.; Fischbeck, K. H. (1991). "Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy". Nature 352 (6330): 77–79. doi:10.1038/352077a0. PMID 2062380. 
  6. ^ Merry, D. E. (2005). "Animal Models of Kennedy Disease". NeuroRX 2 (3): 471–479. doi:10.1602/neurorx.2.3.471. PMC 1144490. PMID 16389310. 
  7. ^ Kennedy, W. R.; Alter, M.; Sung, J. H. (1968). "Progressive proximal spinal and bulbar muscular atrophy of late onset. A sex-linked recessive trait". Neurology 18 (7): 671–680. doi:10.1212/WNL.18.7.671. PMID 4233749.