Myopathy

(Muscle Disease)
*Anwar Wardy W

Kuliah April
2008.FKK-UMJ

Neurologist, Dipl.Forensic Medicine*

Etiology of muscle diseases

Kuliah April
2008.FKK-UMJ

hereditary
autoimmune
systemic disease
toxic
infectious

Neurologist, Dipl.Forensic Medicine*

Muscular dystrophies
childhood disorders with
progressive muscle
weakness
recessive inheritance,
many de novo mutations

Kuliah April
2008.FKK-UMJ

Neurologist, Dipl.Forensic Medicine*

Gowers
sign

X-linked muscular dystrophies

Duchenne (DMD) - small children, Becker

(BMD) - young adults

frequent new mutations
frequent disease: 1:3000 male childbirths
same molecular defect
dystrophin is a major protein of the normal
muscle membrane (sarcolemma)
dystrophin is absent in Duchenne,
underdeveloped in Becker

Kuliah April
2008.FKK-UMJ

Neurologist, Dipl.Forensic Medicine*

Sarcoglycanopathies

(Limb girdle muscular dystrophies)

LGMD1A
LGMD1B
LGMD2A
LGMD2B
LGMD2C
LGMD2D
LGMD2E
LGMD2F
Kuliah April
2008.FKK-UMJ

5q
myotilin
1q
lamin
15q
calpain
2p
dysferlin
13q
-sarcoglycan
17q
-sarcoglycan
4q
-sarcoglycan
5q
-sarcoglycan
Neurologist, Dipl.Forensic Medicine*

Similar phenotype in
sarcoglycanopathies

Kuliah April
2008.FKK-UMJ

Neurologist, Dipl.Forensic Medicine*

Dystrophin-sarcoglycan complex

Kuliah April
2008.FKK-UMJ

Neurologist, Dipl.Forensic Medicine*

Immunfluorescence staining

Normal Duchenne -SGpathy

Dystrophin
-dystroglycan
-sarcoglycan
-sarcoglycan
-sarcoglycan
-sarcoglycan

Kuliah April
2008.FKK-UMJ

utrophin

Neurologist, Dipl.Forensic Medicine*

Myotonic dystrophies
DM1

autosomal dominant
expansion of trinucleotide repeat on
chromosome 19q
normal individuals have 5-35 repeats,
patients have 50-2000 repeats
correlation between number of repeats
severity of disease
associated with systemic abnormalities
Kuliah April
2008.FKK-UMJ

Neurologist, Dipl.Forensic Medicine*

Myotonic dystrophies
PROMM (DM2)

autosomal dominant
chromosome 3q
gene not yet identified

Kuliah April
2008.FKK-UMJ

Neurologist, Dipl.Forensic Medicine*

Muscle channelopathies
Chloride
Sodium
Calcium
Potassium
Kuliah April
2008.FKK-UMJ

Myotonia congenita
Periodic paralysis
Paramyotonia congenita
Periodic paralysis
Malignant hyperthermia
Periodic paralysis
Neurologist, Dipl.Forensic Medicine*

Inflammatory myopathies
Polymyositis / dermatomyositis
characterized by subacute progressive
muscular weakness
dermatomyositis: humorally mediated
polymyositis: cell-mediated immune
process
antigen not known
Kuliah April
2008.FKK-UMJ

Neurologist, Dipl.Forensic Medicine*

Spinal muscular atrophy

autosomal recessive disorder
Incidence: 1 in 6000 births (second most frequent

autosomal recessive disease of childhood)

progressive muscle weakness due to
degeneration of motor neurons in the spinal cord
Gene: SMN (survival motor neuron) mutations or
deletions in 95% of patients
SMN protein promotes axon growth and
maturation
Kuliah April
Neurologist, Dipl.Forensic Medicine*
2008.FKK-UMJ

Normal SMN gene

Large inverted duplication
Telomeric and centromeric copies

Kuliah April
2008.FKK-UMJ

Neurologist, Dipl.Forensic Medicine*

SMN defects
SMA I 2-3 copies of SMN2

Werdnig-Hoffman
SMA II 3 copies of SMN2
SMA III 4-8 copies of SMN2
Kugelberg-Welander

Deletion of SMN1

Kuliah April
Conversion
to SMN2Neurologist, Dipl.Forensic Medicine*
2008.FKK-UMJ

Amyotrophic lateral sclerosis

adult degenerative motor neuron disease
affecting upper and lower motor neurons
with rapid progression

Kuliah April
2008.FKK-UMJ

Neurologist, Dipl.Forensic Medicine*

Amyotrophic lateral sclerosis

10% are familial (autosomal dominant
20% of familial cases have mutations in
the SOD 1 (superoxide dismutase) gene
on chromosome 21q
the mutation causes a toxic gain of
function of the protein
excess of glutamate
Kuliah April
2008.FKK-UMJ

Neurologist, Dipl.Forensic Medicine*

Be a good doctor!

Kuliah April
2008.FKK-UMJ

Neurologist, Dipl.Forensic Medicine*

Thank U
Wassalam, Wr, Wbr

Kuliah April
2008.FKK-UMJ

Neurologist, Dipl.Forensic Medicine*