This document summarizes several types of muscular dystrophies: - Muscular dystrophies are a group of hereditary progressive muscle diseases with unique genetic and phenotypic features. The main types are sex-linked, autosomal recessive, and autosomal dominant. - Duchenne muscular dystrophy is an X-linked recessive disorder caused by the absence of dystrophin. It begins in childhood and is characterized by progressive muscle weakness. - Becker muscular dystrophy is a milder form of X-linked recessive muscular dystrophy. It involves proximal leg muscles and may cause heart failure. - Myotonic dystrophy is an autosomal dominant disorder causing muscle wasting, weakness, and myotonia

1. MUSCULAR
DYSTROPHIES
By,
K.PRIYANGA
CRRI

2.  Muscular dystrophy refers to a group of
hereditary progressive diseases each
with unique phenotypic and genetic
features.

3. TYPES :

5. Classification
Sex-linked: DMD, BMD, EDMD
Autosomal recessive: LGMD, infantile FSHD
Autosomal dominant: FSHD, distalMD, ocular
MD, oculopharyngeal MD.

7. DUCHENNE MUSCULAR
DYSTROPHY
 Also called Pseudo Hypertrophic muscular dystrophy
 X LINKED RECESSIVE disorder
 INCIDENCE : 1 in 5200 live births
 MALES

8. PATHOGENESIS
single gene defect
Xp21.2 region
absent dystrophin(Kunkel
discovered dystrophin
gene)
Guillaume Benjamin Amand
Duchenne
(French neurologist, 1860s)

11. PATHOGENESIS

12. CLINICAL FEATURES
 Apparent by ages 3 and 5 years
 Frequent falls while playing,running, jumping and hopping
 By 5 years , muscle weakness is obvious- Gowers' maneuver, toe walking is
associated with a lordotic posture.
 Loss of muscle strength is progressive (proximal limb muscles and the neck flexors
and leg involvement more)
 By 8 and 10 years -walking may require the use of braces
 By 20 yrs -wheelchair dependent.
 Progressive scoliosis often develops associated with pain which impairs pulmonary
function.

13. Contd..
 By 1 6 一1 8 years , predisposed to fatal pulmonary infections. Other
causes of death include aspiration of food and acute gastric dilation.
 Cardiac cause of death is uncommon despite the presence of a
cardiomyopathy in almost all patients. CCF and arrhythmias are rare
 Intellectual impairment is common

15. GOWER’S MANEUVER :

16. LAB DIAGNOSIS :
 Serum CK levels : elevated between 20 and 100 times normal.
EMG : features typical of myopathy.
Muscle biopsy : muscle fIbers of varying size as well as small groups
of neιrotic and regenerating fIbers. Connective tissue and fat replace lost
muscle fIbers.
 Biopsy of muscle tissue or mutation analysis on peripheral blood leukocytes
by Western blot analysis
 Immunocytochemical Staining : dystrophin antibodies can be
used to demonstrate absence or defIciency of dystrophin localizing to the
sarcolemmal membrane.

18. TREATMENT :
 PREDNISOLONE – 0.75mg/kg given daily for a period of 3 yrs but often
reduced due to side effects
 Physical therapy
 Assisted devices
 Surgery

19. Peter Emil Becker
(German doctor, 1950s)

20. BECKER’S MUSCULAR
DYSTROPHY
 Less severe form of X-linked recessive muscu1ar dystrophy
 It is 10 times less frequent than Duchenne.
 Proxima1 muscles especially of the 1ower extremities are prominently
invo1ved then it becomes more generalized.
 Hypertrophy of muscles of ca1ves is an early and prominent finding
 Patients with Becker dystrophy wa1k beyond age 15
 Menta1 retardation may occur
 Cardiac invo1vement occurs in Becker dystrophy and may result in heart
failure
LAB DIAGNOSIS : Western blot ana1ysis of muscle biopsy shows
reduced amount or abnorma1 size of dystrophin
 Genetic testing revea1s de1etions or duplications of the dystrophin gene in
65% of patients

22. EMERY-DREIFUSS MUSCULAR
DYSTROPHY
 X-linked recessive
 Xq28
 Emerin protein

23. CLINICAL FEATURES : Prominent contractures in early childhood
and teenage years often preceding muscle weakness.
 Muscle weakness affects humeral and peroneal muscles at first and later
spreads to a limb-girdle distribution.
 Cardiomyopathy is potentially life threatening and may result in sudden
death.
LAB DIAGNOSIS : Serum CK may be elevated two- to tenfold.
o EMG is myopathic.
o Muscle biopsy usually shows nonspecific dystrophic features，
 Immunohistochemistry reveals absent Emerin
TREATMENT : Supportive care
Stretching of contractures
Manage cardiac complications

24. LIMB GRIDLE MUSCULAR
DYSTROPHY
 Autosomal
recessive at
chromosome 15q
 Autosomal dominant
at 5q

25. CLINICAL FEATURES :
 Age of onset: 3rd decade
 Initial: pelvic/shoulder muscles (proximal
to distal)
 Similar distribution as DMD
LAB DIAGNOSIS :
 Same as DMD/BMD carriers
 Moderately elevated CPK
 Normal dystrophin

29. FASCIOSCAPULOHUMERAL
MUSCULAR
DYSTROPHY/Landouzy Dejerine
MD
o Etiology : Autosomal dominant - Gene defect (FRG1)
Chromosome 4q35
 Epidemiology - Female > male
Clinical manifestation :
 Age of onset: late childhood/ early adult
 No cardiac, CNS involvement
 Winging scapula –ANGEL WING APPEARANCE
 Markedly decreased shoulder flexion & abduction
 Horizontal clavicles
 Rare scoliosis

30. “Popeye” appearance
 Lack of facial mobility
 Incomplete eye closure
 Pouting lips
 Transverse smile
 Absence of eye and forehead
wrinkles

31. OCULOPHARYNGEAL
MUSCULAR DYSTROPHY
 Autosomal dominant
 Age of onset: 3rd decade
 Characterized by progressive external ophthalmoplegia and Ptosis
 Pharyngeal involvement – Dysarthria,Dysphasia,Repetitive
regurgitation,Frequently choking
 The molecular defect is a subtle expansion of a modest polyalanine
repeat tract in a poly-RNA-binding protein (PABP2) in muscle.
TREATMENT : Cricopharyngeal myotomy may improve
swallowing, although it does not prevent aspiration.
 Eyelid crutches can improve vision when ptosis obstructs vision

32. MYOTONIC
DYSTROPHY/Dystrophia
myotonica
 Myotonic dystrophy type 1 (DM l )- classic disease originally described by Steinert
 Myotonic dystrophy type 2 (DM2) -proximal myotonic myopathy (PROMM).
CLINICAL FEATURES :
o Hatchet-faced Appearance - temporalis,masseter and facial muscle atrophy
o Neck muscles and sternocleidomastoids and distal limb muscles are involved early-
SWAN NECK APPEARANCE
o Weakness of wrist extensors ,finger extensors and intrinsic hand muscles
o Ankle dorsiflexor weakness may cause footdrop..
o Palatal pharyngeal and tongue involvement produce a dysarthric speech ,nasal voice
and swallowing problems.
o Diaphragm and intercostal muscle weakness resulting in respiratory insufficiency.

33. Contd…
o Myotonia which usually appears by age 5 years DEMONSTARTED by
percussion of the thenar eminence,the tongue and wrist extensor
muscles. It causes a slow relaxation of hand grip after a forced
voluntary closure.
o Cardiac disturbances occur commonly in patients with DMl . ECG may
show first-degree heart block .Complete heart block and sudden death can
occur. CCF occurs infrequendy but may result in cor pulmonale secondary to
respiratory failure. Mitral valve prolapse also occurs commonly
o TREATMENT : Phenytoin and Mexiletine
Cardiac pacemaker
Ankle foot prosthesis

34. CONGENITAL MUSCULAR
DYSTROPHY Etiology -Autosomal recessive

36. SUMMARY