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Page 1: Myopathy 03

Kuliah April 2008.FKK-UMJ

*Neurologist, Dipl.Forensic Medicine

Myopathy(Muscle Disease)

•Anwar Wardy W*

Page 2: Myopathy 03

Kuliah April 2008.FKK-UMJ

*Neurologist, Dipl.Forensic Medicine

Etiology of muscle diseases

• hereditary

• autoimmune

• systemic disease

• toxic

• infectious

Page 3: Myopathy 03

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

Page 4: Myopathy 03

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

Page 5: Myopathy 03

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

Page 6: Myopathy 03

Kuliah April 2008.FKK-UMJ

*Neurologist, Dipl.Forensic Medicine

Similar phenotype in sarcoglycanopathies

Page 7: Myopathy 03

Kuliah April 2008.FKK-UMJ

*Neurologist, Dipl.Forensic Medicine

Dystrophin-sarcoglycan complex

Page 8: Myopathy 03

Kuliah April 2008.FKK-UMJ

*Neurologist, Dipl.Forensic Medicine

Normal Duchenne -SGpathy

Dystrophin

-dystroglycan

-sarcoglycan

-sarcoglycan

-sarcoglycan

-sarcoglycan

utrophin

Immunfluorescence staining

Page 9: Myopathy 03

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

Page 10: Myopathy 03

Kuliah April 2008.FKK-UMJ

*Neurologist, Dipl.Forensic Medicine

Myotonic dystrophies

PROMM (DM2)• autosomal dominant

• chromosome 3q

• gene not yet identified

Page 11: Myopathy 03

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

Page 12: Myopathy 03

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

Page 13: Myopathy 03

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

Page 14: Myopathy 03

Kuliah April 2008.FKK-UMJ

*Neurologist, Dipl.Forensic Medicine

Normal SMN gene

• Large inverted duplication

• Telomeric and centromeric copies

Page 15: Myopathy 03

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

Page 16: Myopathy 03

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

Page 17: Myopathy 03

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

Page 18: Myopathy 03

Kuliah April 2008.FKK-UMJ

*Neurologist, Dipl.Forensic Medicine

Be a good doctor!

Page 19: Myopathy 03

Kuliah April 2008.FKK-UMJ

*Neurologist, Dipl.Forensic Medicine

Thank UWassalam, Wr, Wbr