ARTICLE IN PRESS

Current Orthopaedics (2007) 21, 298–300

Available at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/cuor

SYNDROMES

Duchenne muscular dystrophy

Benedict J.A. Lankestera, Michael R. Whitehouseb, Martin F. Garganc,!

a
Specialist Registrar in Trauma and Orthopaedics, Avon Orthopaedic Centre, Southmead Hospital,
Westbury-on-Trym, Bristol BS10 5NB, UK
b
SHO in Trauma and Orthopaedics, Bristol Royal Infirmary, Bristol BS2 8HW, UK
c
Consultant in Trauma and Orthopaedics, Bristol Royal Infirmary and Bristol Hospital for Sick Children, Bristol BS2 8HW, UK

Introduction Clinical presentation and diagnosis

In 1868, Guillaume Duchenne (1806–1875), working in Paris,
described a ‘‘pseudohypertrophic paralysis y which de-
ceives and deludes by giving the limbs the appearance of
great muscularity’’.1 Duchenne muscular dystrophy (DMD) is
the most common childhood neuromuscular disorder, was
the first muscular dystrophy described, is incurable at
present and is invariably fatal. The disease involves a
progressive degeneration of skeletal muscle without asso-
ciated abnormality in the central or peripheral nervous
system.2
Epidemiology and genetics
DMD has an incidence of 2–3 per 100,000, or 1 in 3500 boys.
It is an X-linked recessive disorder, and can therefore
present in XO females (Turner’s syndrome). The incidence is
reducing due to genetic counselling, but 30% of cases involve
spontaneous mutations. The gene involved was first mapped
in 1987 and is located on the short arm of the X chromosome
(Xp21). It codes for dystrophin, a 400 kDa membrane protein
involved in membrane stability. Many different mutations
and deletions have been described, causing varying pheno-
typic severity.
!Corresponding author. Tel.: +44 0117 923 2121;
fax: +44 0117 928 2659.
E-mail addresses: jblankester@aol.com (B.J.A. Lankester),
mike_whitehouse@yahoo.com (M.R. Whitehouse),
martin.gargan@ubht.swest.nhs.uk (M.F. Gargan).
Affected boys are normal at birth and early motor mile-
stones may be appropriate (head control, sitting, etc.).
Independent ambulation is usually delayed, with tiptoe
walking and delayed speech. Steady progression results in a
waddling gait with frequent stumbling and tripping, diffi-
culty standing up and problems with stair climbing.
Proximal muscle weakness precedes distal. Early involve-
ment of the gluteal musculature results in Gower’s sign
(when rising from the floor, the child ‘‘walks’’ his hands up
his thighs due to weakness of hip extension, although widely
described as pathognomonic for DMD, this sign can also be
present in the early stages of discitis).3 Relative sparing of
tibialis posterior function causes tiptoe walking and equi-
novarus deformity (Fig. 1). Another classic feature is calf
pseudohypertrophy due to fibro-fatty infiltration, giving a
firm rubbery feel on palpation.
By the age of 7, walking becomes increasingly difficult.
The knee is hyperextended and the torso tilted back in an
attempt to lock out the hip and knee joints. The ability to
walk is lost on average at 9 years of age (range 6–12), after
which the patient becomes wheelchair bound and may
develop severe flexion contractures. Scoliosis affects 90%,
with progressive collapse into a C shape, and severe pelvic
obliquity leading to loss of sitting balance. Painful hip
dislocation may occur. Most die in their early 20s from
cardio-respiratory failure.
The lack of dystrophin in the cell membrane leads to the
release of creatine kinase (CK) from myocytes, allowing the
diagnosis to be made by markedly increased serum CK levels
(100 ! normal) before symptoms and signs develop. Carrier

0268-0890/$ - see front matter & 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.cuor.2007.07.001
 ARTICLE IN PRESS
Duchenne muscular dystrophy
females, although asymptomatic, will also have CK levels
75% greater than normal. Electromyography will demon-
strate myopathic signs (short duration action potentials and
polyphasic units) and muscle biopsy shows absence of
Figure 1 Equino-varus foot deformity.
Figure 2 Scoliosis pre and post operatively.
299
dystrophin on staining. Genetic testing is available for
confirmation in the affected boy, carrier mother or foetus.
The pattern of physical findings should allow a clinical
diagnosis to be made from the age of 3 years onwards, but it
is often missed at first presentation, leading to the potential
for further affected pregnancies in uninformed families.
A serum CK estimation should be carried out on any boy with
a clumsy or abnormal gait or with an unexplained equinus
deformity.4 The only way reliably to reduce the age of
diagnosis would be to introduce a newborn screening
programme,5 but there are no plans for this in the UK.
The less common but milder Becker muscular dystrophy,
which involves a different type of mutation in the same gene,
causes structurally abnormal dystrophin to be produced.
There is a later age of onset and slower progression.
Treatment
General
Currently, no curative treatment is available for DMD.
Affected boys should be kept ambulatory or standing for as
 ARTICLE IN PRESS
300
long as possible. Regular stretching and strengthening
exercises, night-time splinting, ground-reaction AFOs and a
standing frame may all be useful. Corticosteroids (predni-
solone and deflazacort) have been shown to delay the loss of
muscle strength and function by up to 3 years2 and delay or
prevent the onset of scoliosis,6 but have serious potential
side effects including weight gain and Cushing’s syndrome.
Lower limbs
Serial hip radiographs are used to screen for subluxation.7
Flexion and abduction contractures of the hip may re-
quire percutaneous release. Equinovarus foot deformity is
treated with tendo achillis lengthening and tibialis post-
erior transfer which prolongs the ability to walk.8 Surgical
release of soft tissue knee contractures is less effective.
Aggressive post-operative rehabilitation is needed to pre-
serve overall function, with an avoidance of prolonged
immobilisation.
Spine
The spinal deformity is not amenable to non-surgical
control.2 Early fusion with segmental instrumentation
improves the Cobb angle, delays the deterioration in lung
function and improves survival (Fig. 2).9,10 Timing is crucial,
with a narrow window of opportunity after the curve starts
to develop, but before respiratory and cardiac function are
compromised to the point that the risk of surgery is too
great.2 An FVC less than 30% of the predicted value does not
necessarily preclude surgery.11
A long thoraco-lumbar fusion is performed. In boys with
significant shoulder weakness, any kyphosis should be only
partially corrected to avoid the loss of ability to raise the
hand to the mouth. Blood loss12 and overall complications13
are higher than for idiopathic scoliosis correction. The vital
capacity at the age of 10 is a good predictor of the speed of
progression14 and is useful in identifying those that require
early surgical intervention.
Gene therapy
Although the gene defect responsible for DMD was identified
nearly 20 years ago, the development of effective therapy
has been slow. The large size of the dystrophin gene makes
transfer difficult by the standard vector systems, necessi-
tating the development of novel approaches. A minigene has
been successfully transferred in a mouse model of DMD, with
restoration of normal muscle function.15 Other attempts are
being made to target the downstream effects of DMD, such
as the implantation of myoblasts into dystrophic muscle to
repair a proportion of damaged myofibrils.16 Together these
advances in molecular biology suggest a cure for DMD may
be available in the near future.
B.J.A. Lankester et al.
Acknowledgements
The authors would like to thank Simon Gatehouse and Mike
Gibson, Newcastle General Hospital, for providing the
figures.
References
1. Wenger DR, Rang M. The art and practice of children’s
orthopaedics. Philadelphia, PA: Lippincott; Baltimore: Williams
and Wilkins; 1993.
2. Sussman M. Duchenne muscular dystrophy. J Am Acad Orthop
Surg 2002;10:138–51.
3. Miroysky A, Copeliovich L, Halperin N. Gowers’ sign in children
with discitis of the lumbar spine. J Paediatr Orthop B 2005;
14:68–70.
4. Read L, Galasko CSB. Delay in diagnosing Duchenne muscular
dystrophy in orthopaedic clinics. JBJS [B] 1986;68B:481–2.
5. Parsons EP, Clarke AJ, Bradley DM. Developmental progress in
Duchenne muscular dystrophy: lessons for earlier detection. Eur
J Paediatr Neurol 2004;8:145–53.
6. Alman BA, Raza SN, Biggar WD. Steroid treatment and the
development of scoliosis in males with Duchenne muscular
dystrophy. JBJS [A] 2004;86A:519–24.
7. Chan KG, Galasko CSB, Delaney C. Hip subluxation and
dislocation in Duchenne muscular dystrophy. J Paediatr Orthop
B 2001;10:219–25.
8. Scher DM, Mubarak SJ. Surgical prevention of foot deformity in
patients with Duchenne muscular dystrophy. J Paediatr Orthop
2002;22:384–91.
9. Galasko CSB, Delaney C, Morris P. Spinal stabilization in
Duchenne muscular dystrophy. JBJS [B] 1992;74B:210–4.
10. Bentley G, Haddad FS, Bull TM, Seingry D. The treatment of
scoliosis in muscular dystrophy using modified Luque and
Harrington–Luque instrumentation. J Bone Joint Surg Br 2001;
83:22–8.
11. Marsh A, Edge G, Lehovsky J. Spinal fusion in patients with
Duchenne’s muscular dystrophy and a low forced vital capacity.
Eur Spine J 2003;12:507–12.
12. Fox HJ, Thomas CH, Thompson AG. Spinal instrumentation for
Duchenne’s muscular dystrophy: experience of hypotensive
anaesthesia to minimise blood loss. J Paediatr Orthop 1997;17:
750–3.
13. Ramirez N, Richards BS, Warren PD, Williams GR. Complications
after posterior spinal fusion in Duchenne’s muscular dystrophy.
J Paediatr Orthop 1997;17:109–14.
14. Yamashita T, Kanaya K, Kawaguchi S, Murakami T, Yokogushi K.
Prediction of the progression of spinal deformity in Duchenne
muscular dystrophy: a preliminary report. Spine 2001;26:
223–6.
15. Biggar WD, Klamut HJ, Demacio PC, Stevens DJ, Ray PN.
Duchenne muscular dystrophy: current knowledge, treatment,
and future prospects. Clin Orthop 2002;401:88–106.
16. Sohn RL, Gussoni E. Stem cell therapy for muscular dystrophy.
Expert Opin Biol Ther 2004;4:1–9.