Muscular Dystrophy Duchenne and Becker-Kiener - DMD

Klinische Symptomatik

Duchenne muscular dystrophy is the most common genetic muscular disease in males. Between the end of the first and the fourth year of life, the affected boys show retardation in walking, insecure gait, stumbling, frequent falling and problems in running and climbing stairs. Muscular wasting is first evident at the lower extremities and is combined with pseudohypertrophy of the calves. Creatine kinase levels are regularly and extremely elevated from birth on. Myocardial involvement develops in an age-dependent manner and nearly all patients are affected at later disease stages. Around one third of the patients show psychomotor or mental retardation.

 

Becker-Kiener muscular dystrophy follows a similar, but considerably milder disease course with no mental retardation. Myocardial involvement in young age is observed only rarely, cardiomyopathy and heart failure are common in late stages.

Rarely, dilatative cardiomyopathy can represent the prevailing or only symptom caused by abnormalities in the dystrophin gene.

Genetik

The muscular dystrophies are X-linked recessive conditions and therefore affect predominantly males. The underlying molecular defect is an abnormality in the dystrophin gene, with deletions in approx. 60% of cases and duplications in approx. 6%. Around 34% of cases are caused by point mutations. Around one third of the boys is affected by de novo mutations, in the remaining cases the mother has a carrier status without symptoms. Due to the possibility of an unbalanced X-inactivation female carriers may show mild symptoms in around 8%.

The genetic abnormalities may have arisen in the mother�s germinal cells (gonadal mosaicism). This may account for the fact that the mutation cannot be confirmed from the mother�s peripheral blood cells; however, there is a risk for repeated conduction in about 20% of sporadic cases.

Clinic

male, affected	clinical manifestation	Serume CK concentration
DMD	100%	> 10 fold elevated
BMD	100%	> 5 fold elevated
DMD-dependend dilatative Cardiomyopathy	mostly	elevated
female carrier
DMD	app. 60%	2 - 10 fold elevated
BMD	app. 30%	2 - 10 fold elevated

Distribution of mutation frequencies

Mutation	DMD	BMD
Deletion	app. 65%	app. 85%
Duplication	app. 6 - 10%	app. 6 - 10%
Point mutation	app. 25 - 30%	app. 5 - 10%

Häufigkeit

DMD: in males 1: 3 500
BMD: in males 1: 20 000

 

Diagnostik