Becker's Muscular Dystrophy

The muscular dystrophies (MDs) are a group of inherited disorders characterised by progressive muscle wasting and weakness.¹

Becker's muscular dystrophy (BMD) is similar to the more common muscular dystrophy, known as Duchenne's muscular dystrophy (DMD), but the clinical course is milder. As with DMD, there is muscle wasting and weakness which is mainly proximal. Generally, walking difficulties begin after age 16.²

Female carriers of BMD may be affected, either by some degree of muscle weakness and/or by cardiomyopathy.

The incidence is about 1 in 17,000 live births (about one fifth of DMD incidence).³
BMD is caused by abnormalities of the dystrophin gene, which is responsible for the muscle protein dystrophin. In BMD, abnormal but partly functional dystrophin is produced (cf. DMD, where dystrophin is lacking).¹

• It is inherited in an X-linked recessive pattern. There are various gene defects which give rise to BMD, affecting different parts of the dystrophin gene. The clinical severity of BMD varies, and this is probably due to:
  • Variation in the individual genetic defects, and hence in the dystrophins thus produced.
  • Factors other than the dystrophin gene, which determine the severity of BMD in an individual. In one reported family, two brothers with an identical gene defect had very different clinical manifestations of BMD.²
• BMD can occur as a new mutation. Therefore, not all mothers of BMD patients will be carriers of the gene. BMD can also occur through mosaicism (where only some cell lines are affected).

Symptoms

Symptoms usually begin in childhood. The average age at diagnosis is 11 years, but there is a wide age range. The clinical severity varies.

Early symptoms:

• Delayed walking (sometimes).
• Muscle cramps on exercise.
• Most BMD children are not 'athletic' and may struggle with school sports.

Later symptoms:

• Muscle weakness:
  • Affects proximal muscles of the limbs mainly.
  • May begin in teenage years or twenties, causing difficulty in climbing stairs, fast walking and lifting heavy objects.
• BMD patients can walk independently until age 16 or later (cf. DMD, where patients cannot walk beyond age 12). Walking ability is lost usually at age 40-60, but sometimes earlier, around age 20-30.

Signs:

• Wasting of proximal muscles; hypertrophy of others, particularly the calf muscles.

Other presentations:

• Myoglobinuria.
• Anaesthetic complications - a dangerous, malignant hyperthermia-like reaction with some anaesthetic agents.
• Cardiomyopathy may be the first presentation, if muscle weakness is subclinical.
• There is a higher incidence of learning difficulties, behavioural problems and autistic spectrum disorders, compared with the general population.

Investigations⁵

Initial investigations:

• Serum creatine kinase (CK) - shows moderate-severe increase in BMD (5-50 x normal levels³).
• Raised CK levels in this scenario merit specialist referral for further investigation.

Further investigations:

• Genetic analysis.
• Muscle biopsy - for dystrophin staining.
• Genetic tests and counselling for the family.
• Monitoring for cardiomyopathy (see Cardiac complications below).

• Other muscular dystrophies: differentiation is by the clinical features such as age of onset and pattern of muscle weakness, by muscle biopsy features,¹ and by DNA analysis.
• Other myopathies, e.g. thyrotoxicosis, Cushing's syndrome.
• Neurological causes of muscle weakness: spinal cord lesions, spinal muscular atrophy, motor neurone disease, multiple sclerosis: these conditions may have additional features such as sensory loss, upper motor neurone signs or muscle fasciculation.

Treatment is supportive and includes:

• Exercise programmes and physiotherapy. Recent evidence suggests that exercise training is beneficial.⁶
• Muscle cramps may be helped by night splints, massage or compression treatment using air-filled boots.
• Optimise nutrition:
  • Vitamin D and calcium for bone health
  • Avoid obesity
• After walking ability is lost - wheelchairs and other aids.
• Psychological support and employment advice.
• Monitoring/treatment of complications (see below).

Musculoskeletal complications

• Weakness can lead to joint contractures and scoliosis, which may require orthotic or orthopaedic treatment.
• Complications of immobility, e.g. constipation and osteoporosis.

Cardiac complications⁷

These are:

• Dilated cardiomyopathy:
  • Occurs in most BMD patients^3,8 and is the main factor influencing survival.
  • May be the presenting feature, if muscle weakness is mild. The severity of cardiac involvement does not correlate with the severity of skeletal muscle weakness.⁹
  • Asymptomatic (subclinical) cardiomyopathy is common.¹⁰
  • Symptoms may be non-specific, e.g. fatigue, poor sleep, weight loss, vomiting.
• Arrythmias.

Monitoring and treatment:

• Regular cardiac monitoring from diagnosis/from age 10 years, including:
  • Clinical evaluation.
  • Electrocardiogram (ECG) and echocardiogram - these may be difficult to interpret due to scoliosis.
  • Other possible tests - cardiac MRI, multigated acquisition study (MUGA) and tissue Doppler echocardiography may be more helpful than standard echocardiography.¹¹
• Treatment is with standard regimens, e.g. ACE inhibitors, beta blockers and diuretics for cardiac failure.
• Consider anticoagulation, as thromboembolism risk is increased.
• Nutrition and respiratory function should be optimised.
• Some patients require cardiac transplantation.⁸

Anaesthetic complications⁷

• Life-threatening rhabdomyolysis (malignant hyperthermia-type reaction) to some anaesthetic agents.
• Hyperkalaemia in response to succinylcholine.
• Higher risk of complications due to cardiac disease.
• Careful assessment and monitoring are required with any anaesthetic procedure or surgery.

Other complications

• Respiratory muscle weakness:
  • Depending on the clinical severity of muscle weakness, this is a possible complication. Management would be similar to that for DMD respiratory complications (see separate article Duchenne's Muscular Dystrophy).
• Pain in lower back, spine and legs.¹²

• Life expectancy is reduced; typically BMD patients survive to age 40-50. However, there is a wide variation in the severity of BMD and hence in the prognosis.
• Cardiomyopathy is the cause of death in about half of BMD patients.¹³

Cardiomyopathy risk

• Female carriers of the BMD gene may have an increased risk of cardiomyopathy.
• The extent of the risk is debatable; evidence is conflicting regarding rates of cardiomyopathy in carriers and regarding whether life expectancy is affected.¹⁴
• An international workshop in 2002 recommend regular cardiac screening for BMD carriers,⁷ although this recommendation has been questioned.¹⁴

Manifesting carriers^3,15,16

Most carriers are asymptomatic, but a small percentage (2-5%) may have skeletal muscle symptoms; they are known as manifesting carriers of BMD:

• The reason why the gene manifests in some women but not others, may be through the mechanism of 'X-inactivation', where the normal X chromosome is inactive, and the X chromosome carrying the BMD mutation is the active one.
• As with BMD boys, there may be no family history of the disease.
• Some cases of BMD manifesting carriers were previously diagnosed as having another type of muscular dystrophy but, with new techniques such as dystrophin staining, have been identified as having BMD.

Clinical features:

• There is wide individual variation in the severity of symptoms - from mild muscle weakness, aches or calf muscle enlargement, to a disease as severe as that in boys.
• Onset of symptoms can be in adulthood.
• There is usually some gradual progression of symptoms with time.
• Cardiac involvement can occur.¹⁶

Diagnosis:

• Muscle biopsy looking at dystrophin is usually helpful.
• Genetic tests, including X-inactivation patterns.

Management, follow-up and prognosis: this varies depending on individual severity of symptoms.

1. Emery AE; The muscular dystrophies. BMJ. 1998 Oct 10;317(7164):991-5.
2. McKusick VA, Kniffin CL and O'Neill MJF. Muscular Dystrophy, Becker type; Online Mendelian Inheritance in Man (OMIM), updated 2006
3. Manzur AY, Muntoni F; Diagnosis and new treatments in muscular dystrophies. J Neurol Neurosurg Psychiatry. 2009 Jul;80(7):706-14. [abstract]
4. Factsheet, Becker muscular dystrophy. Muscular Dystrophy Campaign, April 2008.
5. Bandac BR. Becker muscular dystrophy. emedicine, April 2008.
6. Sveen ML, Jeppesen TD, Hauerslev S, et al; Endurance training improves fitness and strength in patients with Becker muscular dystrophy. Brain. 2008 Nov;131(Pt 11):2824-31. Epub 2008 Sep 6. [abstract]
7. No authors listed; Cardiovascular health supervision for individuals affected by Duchenne or Becker muscular dystrophy. Pediatrics. 2005 Dec;116(6):1569-73. [abstract]
8. Connuck DM, Sleeper LA, Colan SD, et al; Characteristics and outcomes of cardiomyopathy in children with Duchenne or Becker muscular dystrophy: a comparative study from the Pediatric Cardiomyopathy Registry. Am Heart J. 2008 Jun;155(6):998-1005. Epub 2008 Mar 19. [abstract]
9. Finsterer J, Stollberger C; Cardiac involvement in Becker muscular dystrophy. Can J Cardiol. 2008 Oct;24(10):786-92. [abstract]
10. Sultan A, Fayaz M; Prevalence of cardiomyopathy in Duchenne and Becker's muscular dystrophy. J Ayub Med Coll Abbottabad. 2008 Apr-Jun;20(2):7-13. [abstract]
11. Meune C, Pascal O, Becane HM, et al; Reliable detection of early myocardial dysfunction by tissue Doppler echocardiography in Becker muscular dystrophy. Heart. 2004 Aug;90(8):947-8.
12. Zebracki K, Drotar D; Pain and activity limitations in children with Duchenne or Becker muscular dystrophy. Dev Med Child Neurol. 2008 Jul;50(7):546-52. [abstract]
13. Finsterer J, Stollberger C; The heart in human dystrophinopathies. Cardiology. 2003;99(1):1-19. [abstract]
14. Holloway SM, Wilcox DE, Wilcox A, et al; Life expectancy and death from cardiomyopathy amongst carriers of Duchenne and Becker muscular dystrophy in Scotland. Heart. 2007 Oct 11;. [abstract]
15. Muscular dystrophy campaign factsheet. Manifesting carriers of Duchenne MD. Updated April 2008.
16. Grain L, Cortina-Borja M, Forfar C, et al; Cardiac abnormalities and skeletal muscle weakness in carriers of Duchenne and Becker muscular dystrophies and controls. Neuromuscul Disord. 2001 Mar;11(2):186-91. [abstract]

• Muscular Dystrophy Campaign: a UK charity giving information and links for all types of muscular dystrophy and related conditions.