Manifesting Carriers of Duchenne Muscular Dystrophy

Although it is a commonly held belief that carriers merely pass on the disease and are unaffected, female carriers can have similar muscular weakness as affected males and for this reason are termed Manifesting Carriers. This condition can occur with no known family history of DMD so all females who are suspected of having any form of muscular dystrophy should be tested to determine if they could be Manifesting Carriers because of the genetic implications

GENETIC ASPECTS

All females inherit two copies of the X chromosome – one from each parent. Each body cell needs only one functional X chromosome. This is randomly determined, so that all females have a mixture of cells in which the active X is either the maternal or the paternal.

All carriers of DMD have some cells in which the active X carries the defect and problems arising from them will obviously depend on the proportion of such cells and their distribution. There is a theory that a compensatory mechanism could cause the ‘normal’ cells to produce enough dystrophin to make up the deficiency – this has yet to be demonstrated. In very rare cases, when the active X carrying the DMD gene is in the cast majority of muscles cells the female carrier will have DMD as severely as affected males. At the other end of the scale the carrier can be unaffected. It is estimated that at least 10% of carriers may have problems, which can vary from a mild generalized weakness to an inability to walk, depending on how many muscles are affected. The weakness can be asymmetric. There is also growing evidence that the heart muscle can be affected in isolation which may not become apparent until later in life.

CLINICAL FEATURES

There appears to be a very wide variety of symptoms in women. Some of these symptoms appear to be bizarre to the practitioner and may lead to mistakes in diagnosis and many unnecessary investigations.

Although most Manifesting Carriers can function normally when well, any mild illness or set back will appear much exaggerated as they are no longer able to make the effort needed.

There may be:

  • A history of weakness and clumsiness in childhood, (e.g. poor performance at all sports, growing pains, cramp etc.)
  • Proximal weakness in muscles leading to:
    • Exhaustion (TATT)
    • Difficulty getting up and down stairs
    • Difficulty getting up from sitting to standing position
    • Awkward gait
  • Myalgia
  • Unexplained abdominal or chest pain
  • Tachycardia of unknown origin
  • Calf muscles look well developed (e.g. footballers legs) because of so-called pseudohypertrophy

DIAGNOSIS

The condition is under-diagnosed. Because of its rarity, few practitioners have enough experience of Duchenne Muscular Dystrophy and there is no easy screening test for Manifesting Carriers, although Creatine Kinase (CK) is usually raised. Many of the symptoms will tend to be blamed on anxiety and exhaustion in caring for a severely disabled child. Also, by comparison, a mother’s complaints will appear trivial to her, so will no be voluntarily reported.

Ideally all known carriers should be assessed at the time of their child’s diagnosis, which is usually carried out in a muscle clinic, but this is seldom done in the United Kingdom. Investigations should include an ECG and a cardiac assessment and possibly a muscle biopsy.

Others suspected of being Manifesting Carriers are also best assessed at a muscle clinic, where there is expertise to deal with such conditions.

MANAGEMENT

Should be aimed at maintaining optimum health:

  • Help with care of affected child(ren)
  • Physiotherapy – gentle stretching exercises
  • Hydrotherapy
  • Use of heat to relieve aching muscles
  • Analgesia to relieve aching muscles
  • HRT may help the older woman
  • ECG and Cardiac assessment should be repeated at appropriate intervals. Problems should initially be referred back to the muscle clinic

Anaesthetics should be avoided if possible, especially succinylcholine. Anaesthetist should be made aware of patient’s genetic status.

PROGNOSIS

There is no known cure. Degeneration is generally much slower than in affected males and most women remain ambulant. Setbacks can cause a short period of rapid degeneration, which many be followed by partial recovery, as opposed to the more gradual inevitable loss of strength experienced by affected males.