Bethlem Myopathy and other diseases related to collagen Type VI

Number 100
Date 23 November 2001

The ENMC consortium on Bethlem myopathy and other diseases related to collagen type VI held its second meeting in Naarden on the 23rd-25th November, 2001. It was attended by seventeen participants from 6 countries: France, Italy, Japan, The Netherlands, Turkey and the United Kingdom.

This workshop was sponsored by the European Community as part of the Myocluster project BETHLEM.

Bethlem myopathy is an inherited disease that affects the skeletal muscles and the substance that surrounds the cells and represents the back bone of many organs (connective tissue) located between the skin and the muscle. The manifestations of the disorder are the following: weakness of the muscles of the limbs and trunk giving rise to difficulties in walking and shortening of muscles, known as contractures, which particularly affect the fingers, elbows and ankles. In 1996 changes in the three collagen 6 (COL6) genes.that carry the code for the three chains of collagen type VI (one of the connective tissue) were shown to cause Bethlem myopathy. The disease is transmitted as an autosomal dominant (one mutation in one of the two copies of the involved gene) disorder.
Recently, members of the ENMC consortium demonstrated that Ullrich scleroatonic muscular dystrophy, that belongs to  the group of congenital muscular dystrophies is due to autosomal recessive (two mutations, each one on one copy of one of  the COL6 genes) mutations in COL6 genes. Ullrich syndrome is an inherited disorder with the following typical manifestations: generalized slowly progressive muscle weakness, contractures of proximal joints (hips, knees, shoulders, elbows) and of the neck due to shortening of muscles (hyperflexibility and/or hyperextensibility of the hand, foot, finger) and breathing difficulties (respiratory failure) at an early age.


The workshop was subdivided according to three main aspects:

1. Bethlem myopathy: clinical aspects, description of new families or families in which  a mutation in COL6 genes was detected. Discussion on the correlation between the location and the nature of the mutation (genotype) and the clinical manifestations (phenotype).

2. Clinical description of families affected by Ullrich scleroatonic muscular dystrophies from all over the world showed that some families have patients with a very severe clinical phenotype and others with mild clinical features overlapping with Bethlem myopathy. At the moment COL6 gene mutations cause only a certain percentage of patients affected by Ullrich scleroatonic muscular dystrophy because some families show no linkage to COL6 genes.
Lessons from the animal model. Molecular (biochemical, molecular biology) and morphological studies on Ullrich syndrome were reported. Molecular diagnosis is now only possible in a research setting but will be available in the near future.

3. The meeting ended with the establishment of clinical criteria for the diagnosis of Ullrich scleroatonic muscular dystrophy.

An extended report of this meeting is published in Neuromuscular Disorders, Volume 12, No.10, December 2002

Prof. Guglielmina Pepe, Bethlem Consortium Chairperson, Rome, Italy

Visit the website of the Myocluster Project BETHLEM at: