Muscular Dystrophies

Dr. Kavita Karmacharya

MD Pathology
 Muscular dystrophies
• Muscular dystrophies are several inherited disorders
of skeletal muscles

• Often beginning in childhood

• Progressive muscle weakness and wasting

 Types
1. X-linked muscular dystrophy
– Duchenne muscular dystrophy (DMD)
– Becker muscular dystrophy (BMD)

2. Autosomal muscular dystrophy

3. Myotonic dystrophy
 X-linked muscular dystrophy
• Most common X-linked muscular dystrophy
(Dystrophinopathies)
- Duchenne muscular dystrophy (DMD)
- Becker muscular dystrophy (BMD)

• Mutations that disrupt the function of larger structural

protein called dystrophin
• DMD : Most severe and most common

• Incidence: 1 per 3500 live male birth

• Clinically manifest by the age of 5 yrs

• With weakness leading to wheel chair dependency by

10 – 12 yrs of age.

• BMD: less common and less severe than DMD

 Pathogenesis
• Loss of function mutations in dystrophin gene on X
chromosome
• Dystrophin
– Largest human genes – 2.3 million base pairs/ 79
exons
– Key component of dystrophin glycoprotein complex
(DGC)
– Located adjacent to plasma membrane in myocytes
– Forms a strong mechanical link between cytoskeleton
inside the myofiber and basement membrane outside
of the cell
• The amino terminus of
dystrophin binds actin
filaments

• The carboxy terminus binds β-

dystroglycan, one of the
transmembrane proteins of
the DGC

• Dystrophin - provide
mechanical stability to the
myofiber and its cell
membrane during muscle
contraction
• Duchenne muscular dystrophy  deletions or frame
shift mutations  total absence of dystrophin

• Becker muscular dystrophy  mutation in dystrophin

gene synthesis of a truncated version of dystrophin
 retains some function

Defects in the complex may lead to small membrane tears

↓
Influx of calcium
↓
Myofiber degeneration
muscular dystrophy.mp4
 Morphology
• The changes in Duchenne and Becker muscular
dystrophy are similar, but differ in degree.
• Muscle biopsy in young boy :
– Segmental myofiber degeneration and regeneration with
atrophic myofibers
– No inflammation
– Myophagocytosis
– Advanced stage
• The muscles are replaced by fat and collagen (fatty
replacement or fatty infiltration)
• Prominent variation in size – small atrophic fibers to
large hypertrophied fibers
• Immunohistochemical
studies for dystrophin

– Absence of the normal

sarcolemmal staining
pattern in Duchenne
muscular dystrophin

– Reduced staining in Becker

muscular dystrophy
 Clinical Features
DMD
• Boys – normal at birth
• Early motor milestones are met/ Walking delayed
• First indication of muscle weakness – clumsiness and
inability to keep up with peers
• Weakness – Pelvic girdle muscles – extending to
shoulder girdle
• Enlargement of muscles of lower legs associated with
weakness - pseudohypertrophy
• Wheel chair dependence – 9.5 years
• Dilated cardiomyopathies/ arrythmias – dystrophin
deficiency in cardiac muscles
• Mental retardation due to cognitive impairment–
functional defect of dystrophin in brain
• Mean age of death – 25 to 30 years – due to respiratory
insufficiency, pulmonary infection / heart failure
• BMD :
– Later childhood, adolescence or adult life

– Course – slowly progressive

– Often with near normal life expectancy

 Diagnosis
• History
• Physical examination
• Laboratory studies :
– Serum creatine kinase
• markedly elevated during first decade of life – due to
ongoing muscle damage
• Falls as the disease progresses and muscle mass is lost
– Genetic studies
• Presence of dystrophin mutation
 Treatment
• Primarily – Supportive care

• Definative therapy – restoration of dystrophin

levels in skeletal and cardiac muscle fibers.
 Autosomal muscular dystrophy
• Pathological features same as DMD and BMD

• Distinct clinical features

Eg Limb girdle muscular dystrophies,
facioscapulohumeral muscular dystrophies.
 Myotonic dystrophy
• Myotonia: sustained involuntary contraction of group
of muscles

• Presents with stiffness and have difficulty in releasing

their grip (for instance after hand shake)
Thank you