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Spinal and bulbar muscular atrophy (SBMA) is an X-linked genetic condition in which degeneration of lower motor neurones results in a slowly progressive neuromuscular disease in affected males. Affected individuals often show signs of androgen insensitivity.

Clinical features

  • Clinical features of SBMA include post-adolescent (typically between the ages of 30 and 50) onset of:
    • lower motor neurone limb weakness, often predominantly proximal and often asymmetric, with symptoms such as:
      • weakness, falls and muscle cramps; and
      • reduced power, fasciculations and depressed deep tendon reflexes;
    • lower motor neurone bulbar dysfunction (though this is rarely the presenting feature of SBMA), with symptoms such as:
      • speech and swallowing difficulty;
      • tongue wasting (especially midline) and fasciculations;
      • fasciculations-myokymia of the perioral region (‘quivering chin’); and
      • dysarthria;
    • absence of upper motor neurone signs (spasticity or hyperreflexia); and
    • adolescent- or adult-onset signs of androgen insensitivity (such as gynaecomastia, testicular atrophy, reduced fertility and erectile dysfunction).
  • Additional supportive features may include:
    • postural or action limb tremor (most commonly in the upper limbs);
    • sensory neuropathy (this tends to present late in the course of the disease);
    • sleep conditions (especially obstructive sleep apnoea);
    • metabolic syndrome (such as raised cholesterol and triglycerides, type 2 diabetes mellitus and fatty liver disease); and
    • elevated creatine kinase (CK).
  • Heterozygous females:
    • are normally asymptomatic due to low levels of circulating androgens;
    • may experience muscle cramps and occasional tremors, but usually do not have significant lower motor neurone disease;
    • may have atypical electromyography (EMG) if they are symptomatic; and
    • are at risk of having affected children.


SBMA is caused by a hemizygous CAG trinucleotide repeat expansion in the androgen receptor (AR) gene located on the X chromosome. CAG expansion length (by number of repeats) should be clinically interpreted in the following ways.

  • 34 CAG repeats or fewer: this result is normal.
  • 35 CAG repeats: this result is of questionable significance. Interpretation requires consideration of clinical features, as well as repeat sizes in other family members.
  • 36 to 37 CAG repeats: this result indicates possible reduced penetrance, and should be interpreted in the context of clinical features and family history.
  • 38 CAG repeats and over: this result can be interpreted as fully penetrant and disease causing. In general, the greater the number of repeats, the earlier the age of disease onset.

Note that there is variable expression in the clinical phenotype of SGMA patients with the same expansion length, even within the same family. It is not possible to predict disease severity or progression in an individual patient based on CAG expansion length.

Inheritance and genomic counselling

SBMA is an X-linked condition. Mothers of affected individuals are likely to be heterozygous carriers for the trinucleotide repeat expansion, especially if there is more than one affected family member. As such, genomic testing of the mother of an affected individual is recommended.

All children of a female carrier of SBMA will have a one-in-two (50%) chance of inheriting the AR repeat expansion. Female carriers may develop symptoms, as outlined above. All males who inherit the variant will be expected to develop symptoms. Fertility issues reduce the chance of affected men passing on the repeat expansion. If an affected male is fertile, all of his female children will be carriers and all of his male children will be unaffected.

The number of CAG repeats is typically stable between generations, with only small changes to repeat length typically seen. For this reason, anticipation (symptoms becoming more severe or appearing at a younger age as the condition is passed down the generations) is relatively rare – though when it does occur, it is more common with male transmission.


Management of those with SBMA is best delivered via a multidisciplinary team, including (though not limited to) neurology, endocrinology, speech and language therapy and physiotherapy. In the UK, there are currently no licensed medications for SBMA.

While gene-directed therapies have shown some promise in animal models of SBMA, at the time of writing there are no active clinical trials of such therapies in humans.

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  • Last reviewed: 31/08/2023
  • Next review due: 31/08/2025
  • Authors: Dr Philip Campbell
  • Reviewers: Dr Emma Matthews, Dr Mary O’Driscoll