Download - Myopathy 03
Kuliah April 2008.FKK-UMJ
*Neurologist, Dipl.Forensic Medicine
Myopathy(Muscle Disease)
•Anwar Wardy W*
Kuliah April 2008.FKK-UMJ
*Neurologist, Dipl.Forensic Medicine
Etiology of muscle diseases
• hereditary
• autoimmune
• systemic disease
• toxic
• infectious
Kuliah April 2008.FKK-UMJ
*Neurologist, Dipl.Forensic Medicine
Muscular dystrophies
• childhood disorders with
progressive muscle
weakness
• recessive inheritance,
many de novo mutations
Gower’s sign
Kuliah April 2008.FKK-UMJ
*Neurologist, Dipl.Forensic Medicine
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 5q myotilin
LGMD1B 1q lamin
LGMD2A 15q calpain
LGMD2B 2p dysferlin
LGMD2C 13q -sarcoglycan
LGMD2D 17q -sarcoglycan
LGMD2E 4q -sarcoglycan
LGMD2F 5q -sarcoglycan
Kuliah April 2008.FKK-UMJ
*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
Normal Duchenne -SGpathy
Dystrophin
-dystroglycan
-sarcoglycan
-sarcoglycan
-sarcoglycan
-sarcoglycan
utrophin
Immunfluorescence staining
Kuliah April 2008.FKK-UMJ
*Neurologist, Dipl.Forensic Medicine
Myotonic dystrophiesDM1• 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 Myotonia congenita
Sodium Periodic paralysis
Paramyotonia congenita
Calcium Periodic paralysis
Malignant hyperthermia
Potassium Periodic paralysis
Kuliah April 2008.FKK-UMJ
*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 2008.FKK-UMJ
*Neurologist, Dipl.Forensic Medicine
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
Conversion to SMN2
Kuliah April 2008.FKK-UMJ
*Neurologist, Dipl.Forensic Medicine
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 UWassalam, Wr, Wbr