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Evidence of left ventricular dysfunction in children with merosin-deficient congenital muscular dystrophy
1MRC Clinical Sciences and the Department of Paediatrics and Neonatal Medicine, Hammersmith Hospital, London, United Kingdom.
Insights
Children with congenital muscular dystrophy and merosin deficiency may develop dilated cardiomyopathy. This condition affects cardiac function, indicated by reduced ejection fraction in affected children.
Area of Science:
- Cardiology
- Neuromuscular Disorders
- Genetics
Background:
- Dystrophin deficiency is linked to dilated cardiomyopathy.
- Congenital muscular dystrophy can involve laminin alpha2 (merosin) deficiency.
- Defects in proteins linking laminin alpha2 to dystrophin are implicated in muscular dystrophy and cardiomyopathy.
Purpose of the Study:
- To investigate cardiac function in children with congenital muscular dystrophy.
- To assess the relationship between laminin alpha2 deficiency and cardiomyopathy in this cohort.
Main Methods:
- Cardiac function assessed using 2-dimensional echocardiography in 16 children.
- Laminin alpha2 expression determined via skin or muscle biopsy.
- Comparison of ejection fraction between merosin-deficient and merosin-positive children.
Main Results:
- Two of six merosin-deficient children had an ejection fraction below 40%.
- Merosin-deficient children showed a significantly lower average ejection fraction (43%+/-11%) compared to merosin-positive children (53%+/-5%, P=.03).
Conclusions:
- Laminin alpha2 deficiency is associated with dilated cardiomyopathy.
- This supports the hypothesis that defects in dystrophin or associated proteins can cause both muscular dystrophy and dilated cardiomyopathy.
Background:
Deficiency of the sarcolemmal protein dystrophin has been linked to dilated cardiomyopathy. Some children with congenital muscular dystrophy have a deficiency of the laminin alpha2 chain of merosin, an extracellular matrix protein linked to dystrophin through a group of glycoproteins. It has been shown that deficiency in one of these glycoproteins is responsible for muscular dystrophy and dilated cardiomyopathy. Children with laminin alpha2 deficiency may be at risk for development of cardiomyopathy.
Methods And Results:
We studied the cardiac function of a cohort of 16 children with congenital muscular dystrophy by using 2-dimensional echocardiography. The expression of the laminin alpha2 of merosin in the patients was determined on a skin or muscle biopsy. Two of 6 merosin-deficient children had an ejection fraction <40%. The average ejection fraction of the merosin-deficient children was 43%+/-11%, which was significantly lower than the merosin-positive children (53%+/-5%, P=.03).
Conclusions:
This study suggests that a deficiency of laminin alpha2 can give rise to dilated cardiomyopathy, supporting the idea that defects of dystrophin, or of associated proteins, can cause dilated cardiomyopathy in addition to muscular dystrophy.