DUCHENNE

MUSCULAR
DYSTROPHY
By Grainne OKeeffe

OVERVIEW

Intro
Aetiology
Pathogenisis
Incidence
Diagnosis
Family support
Clients case
MDT Management

INTRODUCTION

An X linked neuromuscular disease characterised by rapidly progressing

muscle weakness and wasting, (WHO, 2013).
Four phases

Early phase (<6 yrs): clumsy, fall frequently, difficulty jumping or running,
enlarged muscles, contractures.

Transitional Phase (ages 6-9): Trunk weakness (Gowers manouvre), muscle

weakness, heart problems, fatigue.

Loss of ambulation (ages 10-14): by 12 yrs most boys use a powered

wheelchair. Scoliosis due to constant sitting and back weakness, UL
weakness make ADLs difficult (retain use of fingers).

Late stage (15+): life threatening heart and respiratory problems more
prevalent, dyspnea, oedema of the LLs. Average age of death is 19 yrs in
untreated DMD but due to improvements in clinical care in many centres the
average age of death is the late twenties or beyond, (Bushby et al, 2005).

AETIOLOGY

Sex linked: X-linked genetic recessive disorder

Inherited by the carrier mother/sporadic mutation in the

mothers egg cell (1/3 of cases).

Results in an abnormality in the genetic code for the

protein dystrophin resulting in lack of dystrophin.
(Nowak and Davies, 2004)

AETIOLOGY

The dystrophin gene is the largest in the human genome and is

prone to mutation.

60% of dystrophin mutations are large insertions or deletions that

lead to frame shift errors downstream, whereas approximately
40% are point mutations/duplications or small frame shifts/
rearrangements (Hoffman, 2001).

PATHOGENISIS

Dystrophin links the muscle cells to the

extracellular matrix stabilising the
membrane and protecting the
sarcolemma from the stresses that
develop during muscle contraction.

Mechanically induced damage through

eccentric contractions puts a high stress
on fragile membranes and provokes
micro-lesions that could eventually lead
to loss of calcium homeostasis, and cell
death.

Imbalance between necrotic and

regenerative processes: early phase of
disease.

Later phases the regenerative capacity

of muscle fibers are exhausted and
fibers are gradually replaced by
connective tissue and adipose tissue.
(Deconinck and Dan, 2007)

INCIDENCE

Incidence: 1 in 3600-6000 (Emery, 1991), (Bushby et al, 2010), Bradley &

Parsons, 1998)

Between 1 February 1993 to 30 June 1994 DMD incidence was 1 in

12,200 in Northern Ireland (Hughes et al, 1996).

1 in 4200 The Netherlands (Essen et al, 1992).

1 in 5,600 to 1 in 7,700 DBMD males through 5-24 years in four states in

the U.S.A. 1982-2002. (Ciafoloni et al, 2009)

First symptoms noticed on average at 3.6 years (MDSTARnet, 2007)

DIAGNOSIS

Mean age of diagnosis in cases without family hx is >4 years (bushby et al, 2005).

Delay in diagnosis of 2 yrs (Bushby et al, 2005), (Parsons et al, 2004)

(Bushby et al, 2010)

FAMILY SUPPORT

Family support is NB at this time: provide contact with a named

member of staff and provide details of parental support groups .

http://www.parentprojectmd.org

www.dfsg.org.uk

http://www.mdi.ie/index.html

http://www.informingfamilies.ie/

CLIENTS DETAILS

Age: 5 years.

PC: rare Xp21 mutation with Point mutation of exon 7 of the

dystrophin gene resulting in complete absence of dystrophin.

Presentation: (Early ambulatory stage ) - Ambulant, weight 50 th

%, hypertrophy of the calves, +ve Gower's sign, mild lordosis.

Problem List: Poor attention, Speech delay (uses pecs), ?

hyperactivity(reported by mother), proximal weakness of lower
and upper limbs and neck flexors, epistaxis, poor balance, gaitwaddle/flat footed, muscle spasm of calves.

PMHX: Initially presented with developmental delays before he

was diagnosed.

CURRENT PLAN

Corticosteroids: prednisolone 20 mg daily.

Splinting for prevention of contractures at night time.

Check ups with neurologist every 6 months.

Physiotherapy
LTGs

Improve upper limb strength

Improve lower limb strength

Improve balance

Improve participation in play

STGs

Increase throwing distance of bean bag from 1 meter to 1 meters in 3 weeks.

Increase kicking distance of soccer ball while on gym matt from 1 meter to 1 meter in 3 weeks.

Improve one legged stance to 2 seconds in 3 weeks.

Other

Family Support and services

SLT
Psychology
OT

(Bushby et al, 2010)

MDT MANAGEMENT

(Bushby et al, 2010)

REHABILITATION

Management of muscle extensibility and joint contractures:

stretching and positioning, assistive devices for MSK MGT
(orthoses, standing devices), surgical mgt for LL contractures
(Triple arthrodesis).

Improvement, maintenance and support of muscle strength and

function: Recommendations for physical activity - regular
submaximum (gentle) functional strengthening/activity,
including a combination of swimming-pool exercises and
recreation-based exercises in the community.

Steroid prescription and management

(Fowler et al 2002), (Fowler, 1982), (Bushby et al 2010)

CORTIOCOSTERIODS

Currently best treatment available

Improve Muscle Strength and function
Significantly slow the progression of muscle weakness
Prolong ambulation
Delsy the onset of respiratory and/or cardiac dysfunction
Use with caution as side effects include weight gain,
reduced bone density, hyperactivity, failure to gain height.
Prednisone/prednisolone 0.75 mg/kg/day
Deazacort 0.9 mg/kg/day

ORTHOPAEDIC MGT

90 % of boys with DMD are likely to develop a clinically signicant

scoliosis.

Surgery has shown to be effective in correcting scoliosis and Success

rates are likely to be highest and complication rates lowest if surgery
is performed when the spine is still mobile at a Cobb angle of 2040%
(Cervellati et al, 2004) .

Spinal bracing for those unable for surgery.

Triple arthrodesis may be required

Bone health: Fractures (long bone and vertebral)Osteopenia,

Osteoporosis Kyphoscoliosis, Bone pain, Reduced QOL DEXA scans,
serum/urine tests, spine readiograph Vit D, Calcium,
Biphosphonates.

SCOLIOSIS MGT

(Eagle et al, 2007) KaplanMeier survival plot to show the impact of spinal surgery and
ventilation on survival. Survival curves are significantly different p=0.0001.

CARDIAC DYSFUNCTION + MGT

Death is due to cardiac dysfunction in 10% of cases (Gulatie et al,

2005).

Dilated cardiomyopathy: A condition in which the heart becomes

weakened and enlarged. As a result, the heart cannot pump enough
blood to the rest of the body.

Death due to cardiomyopathy is expected to rise now that life

expectancy increases, (Bushby et al, 2003).

It is estimated that 2030% of DMD boys have left ventricular

impairment on echocardiography by age 10 years (Bushby et al,
2005).

Cardiac mgt should be implemented at diagnosis as clinical

symptoms appear later than initial cardiac dysfunction,
echocardiogram & electrocardioram at 6 yrs, every 2 yrs up to age
10 and annually after 10 yrs +.

ACE and beta blockers

(American academy of Paediatrics, 2005)

Respiratory MGT

Panel 1: Respiratory interventions indicated in patients

with Duchenne
muscular dystrophy
Step 1: volume recruitment/deep lung in ation
technique
Volume recruitment/deep lung in ation technique (by
self-in ating manual ventilation bag
or mechanical insu ationexsu ation) when FVC
<40% predicted
Step 2: manual and mechanically assisted cough tech
Respiratory infection present and baseline peak
cough ow <270 L/min*
Baseline peak cough ow <160 L/min or maximum
expiratory pressure <40 cm water
Baseline FVC <40% predicted or <125 L in older
teenager/adult
Step 4: daytime ventilation
In patients already using nocturnally assisted
ventilation, daytime ventilation is
indicated for:
Self extension of nocturnal ventilation into waking
hours
Abnormal deglutition due to dyspnoea, which is
relieved by ventilatory assistance
Inability to speak a full sentence without
breathlessness, and/or
Symptoms of hypoventilation with baseline SpO2
<95% and/or blood or end-tidal CO2
>45 mm Hg while awake
Continuous non-invasive assisted ventilation (with
mechanically assisted cough) can
facilitate endotracheal extubation for patients who
were intubated during acute
illness or during anaesthesia, followed by weaning to
nocturnal non-invasive assisted
ventilation, if applicable

Step 3: nocturnal ventilation

Nocturnal ventilation is indicated in patients
who have any of the following:
Signs or symptoms of hypoventilation
(patients with FVC <30% predicted are at
especially high risk)
A baseline SpO2
<95% and/or blood or end-tidal CO2
>45 mm Hg while awake
An apnoeahypopnoea index >10 per hour on
polysomnography or four or more
episodes of SpO2
<92% or drops in SpO2
of at least 4% per hour of sleep
Optimally, use of lung volume recruitment and
assisted cough techniques should always
precede initiation of non-invasive ventilation
Step 5: tracheostomy
Indications for tracheostomy include:
Patient and clinician preference
Patient cannot successfully use non-invasive
ventilation
Inability of the local medical infrastructure to
support non-invasive ventilation
Three failures to achieve extubation during
critical illness despite optimum use of
non-invasive ventilation and mechanically
assisted cough
The failure of non-invasive methods of cough
assistance to prevent aspiration of
secretions into the lung and drops in oxygen
saturation below 95% or the patients
baseline, necessitating frequent direct tracheal
suctioning via tracheostomy

PSYCHOSOCIAL MGT
Psychosocial AX
Emotional adjustment/coping
Neurocognitive
Autism spectrum disorders
Social work
Psychosocial Interventions
Psychotherapy
Pharmacological interventions
Educational interventions
Social interaction interventions
Care/support interventions

OTHER MDT ROLES

Nutritionist/dietician: to guide the patient to maintain good

nutritional status to prevent both under nutrition/malnutrition
and being overweight/obese, and to provide a well-balanced,
nutrient-complete diet.

SLT: To monitor and treat swallowing problems, to prevent

aspiration and weight loss, and to assess and treat delayed
speech and language problems.

Clinical Nurse specialist: Family Support and Services

OT: Continue previous measures Provision of appropriate

wheelchair and seating, and aids and adaptations to allow
maximum independence in ADL, function, and participation.

REFERENCES

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/Becker muscular dystrophy among males aged 5-24 years - four states, 2007. MMWR Morb Mortal
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Hoffman EP, Dressman D (2001) Molecular pathophysiology and targeted therapeutics for muscular
dystrophy. Trends Pharmacol Sci 22: 465470

Nowak, K. J., & Davies, K. E. (2004). Duchenne muscular dystrophy and dystrophin: pathogenesis
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Ouyang L, Grosse SD, Kenneson A. Health Care Utilization and Expenditures for Children and Young
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Hughes, M. I., Hicks, E. M., Nevin, N. C., & Patterson, V. H. (1996). The prevalence of inherited
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DEVELOPMENTAL PROGRESS
(Parsons et al, 2004)

Milestone

Late/never
achieved
(%) case
numbers

Median age
(range
achieved)
(months)

Walking alone

(89%) 16/18

16 (1327)

Sitting alone

(67%) 12/18

8 (516)

Meaningful
sentences

(53%) 9/17

29 (2043)

Single words

(47%) 8/17

13 (924)