Patient professional reference
The muscular dystrophies are a group of inherited disorders characterised by progressive muscle wasting and weakness, of which Duchenne muscular dystrophy (DMD) is the most common.
DMD is an X-linked recessive condition which presents in early childhood and inevitably progresses. Some carriers also have symptoms. New mutations are common in DMD; this means that female relatives of a child with DMD are not necessarily carriers of the gene.
DMD affects about 1 in 3,500 newborn males.
DMD occurs as a result of mutations (mainly deletions) in the dystrophin gene (locus Xp21.2). Mutations lead to an absence of or defect in the protein dystrophin, which results in progressive muscle degeneration. The dystrophin gene is large and many different mutations can affect it.In DMD, no dystrophin is produced (in Becker's muscular dystrophy, there is abnormal dystrophin).
There is progressive proximal muscular dystrophy with characteristic pseudohypertrophy of the calves. All patients have symptoms by age 3 years but diagnosis is often delayed. Presenting features are:
- Motor milestones delayed.
- Inability to run - waddling gait when attempting to do so.
- Other gait signs - no spring in the step, cannot hop or jump; toe walking; falls.
- Gower's sign - 'climbing up legs' using the hands when rising from the floor.
- Hypertrophy of calf muscles (and possibly other muscles too, including the deltoid, quadriceps, tongue and masseters).
Non-locomotor presenting symptoms:
- Speech delay or global developmental delay.
- Failure to thrive.
- Abnormal LFTs (raised AST or ALT).
- Anaesthetic complications - eg, myoglobinuria, rhabdomyolysis or malignant hyperthermia after certain anaesthetics.
- Fatigue - this is common.
Assessment and diagnosis - general points
- Awareness: consider DMD in any boy who is not walking by 18 months, who has delayed motor milestones or global developmental delay.
- Aim to make the diagnosis early, to allow genetic counselling for the family - important if parents are considering another pregnancy.
- NB: it is important to watch the child running and rising from the floor. Look for a waddling gait and Gowers' sign. This is more useful than formal examination in a young child.
- Remember that DMD is a devastating diagnosis - follow good practice for disclosing bad news.
Patients with suspected DMD
- The initial investigation is serum creatine kinase (CK):
- In DMD the CK level is very high (10-100 x normal from birth).
- A normal CK at presentation excludes DMD. However, later on CK levels fall due to muscle wasting; therefore, it is not reliable as a screening test in those who are already wheelchair users.
- The precise diagnosis is best achieved by a combination of:
- Genetic analysis - can identify most (but not all) of the DMD mutations.
- Muscle biopsy - with assay for dystrophin protein.
- Clinical observation of muscle strength and function.
Possible carriers of the gene
- Carrier status can usually be identified by genetic analysis. Also, serum CK is usually high in carriers.
- For a subsequent pregnancy, prenatal diagnosis is often (but not always) possible using genetic analysis.
- Other types of muscular dystrophy - particularly Becker's muscular dystrophy, which is similar but progresses more slowly.
- Other myopathies.
- Neurological causes of muscle weakness - eg, spinal cord lesions, spinal muscular atrophy, motor neurone disease, multiple sclerosis. These conditions are likely to have additional features, such as sensory loss, upper motor neurone signs or muscle fasciculation.
- Increased transaminases (aspartate aminotransferase and alanine aminotransferase, which are produced by muscle as well as liver cells). The diagnosis of DMD should thus be considered before liver biopsy in any male child with increased transaminases.
Multidisciplinary care is essential, including psychosocial management. No specific aspect of care can be taken in isolation.
Initial management - after diagnosis
- Information and support for the family.
- Genetic diagnosis and counselling.
- Referral to a specialist and multidisciplinary team.
- Immunisations - influenza and pneumococcal.
Early-stage management - while the child is walking, up to age 11 years
- Physiotherapy for advice on stretching, to prevent contractures.
- Later, knee-foot-ankle orthoses may help prolong walking.
- Serial casting of the ankles may be helpful (may prevent the need for surgical release of the Achilles tendon).
- Optimise bone health:
- Vitamin D and calcium dietary advice or supplements.
- Bisphosphonates if vertebral fracture occurs.
Management after walking ability is lost
Boys with DMD lose independent mobility around age 8-11 years. Once this occurs, management involves:
- Help with mobility - usually an electric wheelchair.
- Orthopaedic care - orthotics or surgery for contractures and scoliosis. Scoliosis is usually progressive and treated with surgery.
- Cardiac and respiratory surveillance is important (see 'Management of respiratory and cardiac complications', below).
- Support and adaptations for school.
- Counselling and support with adolescence.
Management in later stages
This may be from the boy's late teens, and may involve:
- Support for increasing weakness and fatigue; wheelchair and other living adaptations are needed.
- Optimise respiratory and cardiac treatments (see 'Management of respiratory and cardiac complications', below).
- Nutritional advice.
- Respite care for the family.
- Palliative care.
- Planning ahead and end-of-life directives; be aware that deterioration can occur suddenly in the later stages of DMD.
- Patients with DMD may experience a variety of life-threatening complications during and after general anaesthesia, including malignant hyperthermia and disease-related cardiac complications.
- Anaesthetic procedures require careful pre-operative assessment and close monitoring.
- Avoid certain anaesthetic drugs (risk of complications - see 'Presentation', above).
Potential future developments include gene therapy and exon skipping.Exon skipping is used to cause cells to skip over faulty sections of the genetic code.[14, 15] There have been encouraging results obtained with adult stem cells to treat muscular dystrophies.
- Joint contractures.
- Respiratory complications:
- Respiratory muscle failure is progressive, leading to hypoventilation, loss of coughing, and respiratory infections.
- Early symptoms may be nonspecific, so awareness and monitoring are needed.
- Respiratory failure is the usual cause of death.
- Cardiac complications:
- The severity of cardiomyopathy and congestive heart failure may not parallel the severity of skeletal muscle disease. Atrial and ventricular arrhythmias may be life-threatening. The degree of hypoventilation and pulmonary dysfunction also affects cardiac function in muscular dystrophy.
- Dilated cardiomyopathy is common, because cardiac muscle is also affected by the disease. Symptoms are less likely and usually occur later in the course of DMD. Only a minority of patients die from cardiac complications.
- Smooth muscle can also be affected, causing gastrointestinal symptoms such as gastric dilation or pseudo-obstruction.
- Educational: about 20% of DMD patients have learning difficulty. This is nonprogressive and may affect verbal ability more than other performance.
- Complications of immobility and/or steroids - eg, constipation, osteoporosis, obesity, hypertension.
- Weight loss can occur in the late stage of DMD.
- Anaesthetic complications (see 'Presentation' and 'Management', above).
Management of respiratory and cardiac complications
Respiratory function tends to decline after the child needs a wheelchair. The problems are:
- Reduced ventilation - initially during sleep.
- Loss of effective cough - leading to infections and atelectasis.
- Early symptoms are often nonspecific - eg, morning drowsiness, headaches, nausea, fatigue, poor concentration.
Good care improves symptoms and survival. Recommendations are:
- Monitoring - eg, by forced vital capacity (FVC), cough peak flows and pulse oximetry.
- Regular review by a respiratory physician if using a wheelchair/reduced FVC/age 12 onwards.
- Treat chest infections promptly.
- Non-invasive ventilation (NIV) relieves symptoms and prolongs survival. There are various types and options.
- Assist coughing and airway clearance - eg, by manual techniques, cough assist devices or tracheostomy.
- Symptoms of cardiac failure may go unrecognised.
- Early screening should be in place to identify cardiomyopathy before it becomes symptomatic - eg, six-monthly cardiology review from early childhood.
- Standard tests such as electrocardiogram (ECG) and echocardiogram (echo) may be difficult to interpret due to scoliosis.
- Cardiac impairment and arrhythmias are treated in the standard way using angiotensin-converting enzyme (ACE) inhibitors, diuretics and beta-blockers.
- Treat nocturnal hypoventilation (which exacerbates cardiac problems).
- If glucocorticoids are given, increased cardiac monitoring is needed, and watch weight gain and blood pressure.
- Patients are at increased risk of thromboembolism; consider anticoagulation if there is severe cardiac impairment.
- There is progressive muscle weakness.The hand muscles are often spared until late on, and extraocular muscle function is preserved.
- Affected boys are normally confined to a wheelchair by 12 years of age and die from respiratory or cardiac complications in their 20s or 30s.
- Severity and progression vary between individuals.
Female carriers of Duchenne muscular dystrophy
- Female carriers of the DMD 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.
- One review suggests that there is a 10% lifetime risk of cardiomyopathy for DMD carriers.
- An international workshop in 2002 recommended regular cardiac screening for all DMD carriers.However, this recommendation has been questioned.
Most carriers are asymptomatic, but a small percentage (2-5%) may have skeletal muscle symptoms; they are known as manifesting carriers of DMD:
- The reason why the gene manifests in some women but not in others may be through the mechanism of 'X-inactivation', where the normal X chromosome is inactive and the X chromosome carrying the DMD mutation is the active one.
- As with DMD boys, there may be no family history of the disease.
- Some cases of DMD-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 DMD.
- 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.
- 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.
Further reading and references
Muscular Dystrophy, Duchenne Type, DMD; Online Mendelian Inheritance in Man (OMIM)
Ataluren for treating Duchenne muscular dystrophy with a nonsense mutation in the dystrophin gene; NICE Highly Specialised Technologies Guidance, July 2016
Manzur AY, Kinali M, Muntoni F; Update on the management of Duchenne muscular dystrophy. Arch Dis Child. 2008 Nov93(11):986-90. Epub 2008 Jul 30.
Beytia Mde L, Vry J, Kirschner J; Drug treatment of Duchenne muscular dystrophy: available evidence and perspectives. Acta Myol. 2012 May31(1):4-8.
Bushby K, Finkel R, Birnkrant DJ, et al; Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010 Jan9(1):77-93. doi: 10.1016/S1474-4422(09)70271-6. Epub 2009 Nov 27.
Leung DG, Wagner KR; Therapeutic advances in muscular dystrophy. Ann Neurol. 2013 Sep74(3):404-11. doi: 10.1002/ana.23989.
Angelini C, Tasca E; Fatigue in muscular dystrophies. Neuromuscul Disord. 2012 Dec22 Suppl 3:S214-20. doi: 10.1016/j.nmd.2012.10.010.
Bushby K, Finkel R, Birnkrant DJ, et al; Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol. 2010 Feb9(2):177-89. doi: 10.1016/S1474-4422(09)70272-8. Epub 2009 Nov 27.
Manzur A, Kuntzer T, Pike M, et al; Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2008 Jan 23(1):CD003725.
Cheuk DK, Wong V, Wraige E, et al; Surgery for scoliosis in Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2015 Oct 110:CD005375. doi: 10.1002/14651858.CD005375.pub4.
Respiratory Care of the Patient with Duchenne Muscular Dystrophy - ATS Consensus Statement 2004; American Thoracic Society
Birnkrant DJ, Panitch HB, Benditt JO, et al; American College of Chest Physicians consensus statement on the respiratory and related management of patients with Duchenne muscular dystrophy undergoing anesthesia or sedation. Chest. 2007 Dec132(6):1977-86.
Gurnaney H, Brown A, Litman RS; Malignant hyperthermia and muscular dystrophies. Anesth Analg. 2009 Oct109(4):1043-8. doi: 10.1213/ane.0b013e3181aa5cf6.
Sienkiewicz D, Kulak W, Okurowska-Zawada B, et al; Duchenne muscular dystrophy: current cell therapies. Ther Adv Neurol Disord. 2015 Jul8(4):166-77. doi: 10.1177/1756285615586123.
Strehle EM, Straub V; Recent advances in the management of Duchenne muscular dystrophy. Arch Dis Child. 2015 Dec100(12):1173-7. doi: 10.1136/archdischild-2014-307962. Epub 2015 Jul 7.
Goyenvalle A, Seto JT, Davies KE, et al; Therapeutic approaches to muscular dystrophy. Hum Mol Genet. 2011 Apr 1520(R1):R69-78. doi: 10.1093/hmg/ddr105. Epub 2011 Mar 24.
Konieczny P, Swiderski K, Chamberlain JS; Gene and cell-mediated therapies for muscular dystrophy. Muscle Nerve. 2013 May47(5):649-63. doi: 10.1002/mus.23738. Epub 2013 Mar 29.
Meregalli M, Farini A, Colleoni F, et al; The role of stem cells in muscular dystrophies. Curr Gene Ther. 2012 Jun12(3):192-205.
Romfh A, McNally EM; Cardiac assessment in duchenne and becker muscular dystrophies. Curr Heart Fail Rep. 2010 Dec7(4):212-8. doi: 10.1007/s11897-010-0028-2.
Guidelines for the respiratory management of children with neuromuscular weakness; British Thoracic Society (2012)
No authors listed; Cardiovascular health supervision for individuals affected by Duchenne or Becker muscular dystrophy. Pediatrics. 2005 Dec116(6):1569-73.
Mavrogeni S, Markousis-Mavrogenis G, Papavasiliou A, et al; Cardiac involvement in Duchenne and Becker muscular dystrophy. World J Cardiol. 2015 Jul 267(7):410-4. doi: 10.4330/wjc.v7.i7.410.
Fairclough RJ, Bareja A, Davies KE; Progress in therapy for Duchenne muscular dystrophy. Exp Physiol. 2011 Nov96(11):1101-13. doi: 10.1113/expphysiol.2010.053025. Epub 2011 Jul 31.
Desguerre I, Christov C, Mayer M, et al; Clinical heterogeneity of duchenne muscular dystrophy (DMD): definition of sub-phenotypes and predictive criteria by long-term follow-up. PLoS One. 20094(2):e4347. doi: 10.1371/journal.pone.0004347. Epub 2009 Feb 5.
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
Manzur AY, Muntoni F; Diagnosis and new treatments in muscular dystrophies. J Neurol Neurosurg Psychiatry. 2009 Jul80(7):706-14.
This particular problem started about 5 years ago, however it was much more mild and not as worrying. The muscle twitches originally started in my feet and legs, and was more of an annoyance than...rsarah21
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