Duchenne muscular dystrophy Flashcards
DMD
rare and severe genetic condition that causes muscle weakness and progressive disability from childhood to adulthood.
caused by a mutation in the gene that codes for dystrophin, a structural protein important for muscle cells.
forms part of a complex that anchors actin to the cell membrane, and is important in stabilising the muscle cell membrane. Loss of dystrophin expression results in myofiber loss, resulting in contraction induced muscle damage and degeneration..
boys affected by DMD
Boys experience severe, progressive and relentless muscle weakness secondary to muscle inflammation, degeneration, fatty infiltration and fibrosis of muscle fibres.
As the condition advances, there is progressive muscle weakness and atrophy, as well as pseudohypertrophy of muscle (due to fatty fibrous replacement of muscle), most often noticed in the calves as seen in the picture above.
clinical features of DMD- 0-2 years old
Below two years of age, there may be delay in attainment of motor milestones.
Boys not walking by 18 months of age should be referred for further assessment
clinical features- 2-3 years old
Enlarged calf muscles (i.e. calf hypertrophy)
Frequent falls
Tiredness/fatigability
Delayed motor milestones: poor head control persists, abnormal run, struggling with steps, unable to jump.
Learning difficulties, speech delaysand behavioural problems are common.
clinical features of DMD- 3-4 years old
Difficulties in running and climbing stairs
Struggling to getting up from the floor (Gower’s manoeuvre)
Frequent falls
Struggling to jump
Persistent tip-toe walking
genetics of DMD
DMD is caused by mutations in the dystrophin gene with 79 exons.
Which is the largest known human gene
and encodes a structural protein that link cytoskeletal actin molecule and extracellular matrix through forming a network with dystrophin-associated glycoprotein complex [DAGC].
Without functional dystrophin scaffolding, muscle is subjected to progressive contraction induced muscle damage.
Any mutations that disrupt the reading frame or point mutations that generate a premature stop codon disrupts the dystrophin protein translation, leading to DMD
different mutations in dystrophin gene
The majority of patients have a deletion (~68%)
or duplication (~11%) of one or more exons,
while ~21% have a small mutation, either involving a point mutation that induces a premature stop codon (nonsense mutations, 10% of all mutations)
Or involving a small deletion or insertion that disrupts the reading frame (7%).
or disrupting a splice site (3%)
