Bethlem myopathy is caused by mutations (changes) in the COL6A1, COL6A2, or COL6A3 genes. These genes each provide instructions for making one component of a protein called type VI collagen. This protein plays an important role in the muscles, particularly skeletal muscles. Type VI collagen makes up part of the extracellular matrix, an intricate lattice that forms in the space between cells and provides structural support to the muscles.
Mutations in the type VI collagen genes result in the formation of abnormal type VI collagen or reduced amounts of type VI collagen. This decrease in amounts of normal type VI collagen disrupts the extracellular matrix surrounding muscle cells, which leads to the progressive muscle weakness and other signs and symptoms of Bethlem myopathy.
Bethlem myopathy is typically inherited in an autosomal dominant manner, meaning one copy of the altered gene in each cell is sufficient to cause the disease. We inherit one copy of each of our genes from our mother and the other from our father. Many cases of Bethlem myopathy result from new (de novo) mutations in the gene, meaning the mutations were not inherited from either parent. When people who have a new mutation in a gene causing Bethlem myopathy go on to have children, each of their children will have a 50% chance of inheriting the disease.
In some cases, a person who has Bethlem myopathy inherited the mutation from one affected parent. In these cases, future children of this parent will also have a 50% chance to inherit the disease. The parent who has the disease may be so mildly affected that they didn’t know they were showing symptoms of the disease at all.
In rare cases, Bethlem myopathy is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive disease each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the disease. These individuals are known as carriers. When two carriers of a gene mutation causing Bethlem myopathy have children, for each child there is a:
Rarely, severe muscle weakness may lead to respiratory difficulties in later life. Bethlem myopathy is caused by mutations (changes) in the COL6A1, COL6A2, or COL6A3 genes. Most cases are inherited in an autosomal dominant manner, but in rare cases the disease is autosomal recessive.
Bethlem myopathy mainly affects skeletal muscles, which are the muscles used for movement. People with this disease experience progressive muscle weakness and joint stiffness (contractures) in their fingers, wrists, elbows, and ankles. The features of Bethlem myopathy can appear at any age. In some cases, the symptoms start before birth with decreased fetal movements. In others, low muscle tone (hypotonia) and a stiff neck (torticollis) develop during infancy. During childhood, developmental delay may be noted. For example a baby with Bethlem myopahy may learn to sit by themselves or walk later than usual. In some, symptoms don’t occur until adulthood, when a person may notice muscle weakness. By the age of 50-years-old, approximately two-thirds (66%) of people with Bethlem myopathy will need to use a walker, cane, or wheelchair.
In addition to the muscle problems, some people with Bethlem myopathy have skin abnormalities. These abnormalities may include small bumps called follicular hyperkeratosis that develop around the elbows and knees or soft, velvety skin on the palms and soles. Some people may also have wounds that split open with little bleeding and widen over time to create shallow scars. Rarely, individuals with Bethlem myopathy may develop breathing problems as the disease progresses
The common symptoms of Bethlem myopathy are:
There may be some symptoms not listed above. If you have any concerns about a symptom, please consult your doctor.
Bethlem myopathy is typically diagnosed based on a clinical evaluation that identifies signs and symptoms typical of people with the disease. A healthcare provider may recommend additional laboratory test including:
Genetic testing of the COL6A1, COL6A2, and COL6A3 genes can confirm the diagnosis.
The treatment for Bethlem myopathy is symptomatic and supportive. This means that treatment is directed at the symptoms of each affected individual.
There is currently no cure for the disease, and there are no specific medications for Bethlem myopathy. In most cases, physical therapy, stretching exercises, braces, splints, and mobility aids such as a walker or wheelchair may be used to help people with Bethlem myopathy. In rare cases, surgery may be needed to help with joint contractures or scoliosis. Clinical trials are currently testing other possible treatments that could help slow the progression of symptoms of Bethlem myopathy.
The main aim of physiotherapy is to keep the muscles as active as possible and to prevent or slow the progression of joint contractures (tightness). Individuals with Bethlem myopathy are encouraged to remain as active as possible. Swimming is a particularly good form of exercise.