What is Bethlem Myopathy?

Bethlem myopathy is a rare disease affecting the connective tissues and the skeletal muscles causing muscle weakness and joint stiffness. Bethlem myopathy is a muscle disorder condition. It is a hereditary condition and it is named after the Dutch doctors Bethlem and van Jijngaarden, who first described the condition in 1976. Bethlem myopathy is a type of congenital muscular dystrophy disease, though it is less severe and slow progressing as compared to other muscular dystrophy conditions.

The disease presents with mild clinical symptoms with proximal muscle weakness along with early contractures in the fingers. The absence of cardiomyopathy and pseudohypertrophic calves are the distinctive features of Bethlem myopathy. The onset of the disease can occur at any time in a person's life, including in vitro as well. The genes responsible for this condition are all associated with collagen type IV in the body. These include the COL6A1, COL6A2, or the COL6A3 genes.

Cause of Bethlem Myopathy

The main cause of Bethlem myopathy is mutations in one of the collagen type IV genes. These are called COL6A1, COL6A2, and COL6A3. Mutation results in production of either abnormal collagen type IV protein or it lowers the levels of collagen IV protein in the body. As collagen is the primary protein of connective tissues and it provides support for the muscle cells, Bethlem myopathy affects the muscles in the body.

The exact reason why these genetic mutations occur in the body and lead to the disease is not completely understood. However, the muscle cells of people suffering from Bethlem myopathy are more sensitive to cell death causing change in the mitochondria, which is the energy supplying part of the cells.

Inheritance of Bethlem Myopathy

Bethlem myopathy is generally an inherited disease. It is known to be 'autosomal dominant', meaning that one copy of the mutated gene, inherited from any parent, is enough to give rise to the disease. There is a 50 percent chance that the children of a person suffering from Bethlem myopathy will also inherit the condition. However, some people are diagnosed with Bethlem myopathy and neither of the parents seem to be having it. This means that the parents could be affected so mildly that they never realized that they have the condition. It could also mean that the gene mutation has occurred for the first time in the affected individual.

Symptoms of Bethlem Myopathy

People suffering from Bethlem myopathy experience slowly progressing muscle weakness and also develop joint stiffness in their wrists, elbows, fingers, and ankles. This type of stiffness can restrict movement. The severity of symptoms varies from individual to individual and as with the disease, can appear at any age.

Initial symptoms of Bethlem myopathy can present at any time from birth to adulthood to even in vitro. The symptoms are very variable. For most patients with weakness and contractures, the symptoms of Bethlem myopathy that accompany the disease are known to become worse with age. However, this happens very slowly and varies from person to person. Many adults go through their life being unaware of any muscle weakness or experience only slight contractures. While some need to use equipment to remain mobile such as a cane, wheelchair, or crutches.

Symptoms of Bethlem myopathy during childhood, symptoms can present as hypotonia (floppiness of muscles), joint laxity, delayed motor milestones in a baby, muscle weakness, club foot or taipes, stiffness in the neck known as torticollis, etc. Contractures (tightness) can also occur in the hips, knees, ankles, and elbows. The contractures vary from patient to patient and can also come and go over a period of time. Stiffness of the spine is also known to develop over the years.

If symptoms of Bethlem myopathy present during adulthood then patients can have tight tendons at the back of their ankles along with muscle tightness of other joints such as knees, elbows, and the joints in the back. Muscles in the hands are also particularly affected. Contractures of the finger muscles is a typical symptom of Bethlem myopathy.

Other symptoms of Bethlem myopathy can include:

  • Poor stamina
  • Low tolerance for exercising
  • Difficulty in walking upstairs or doing tasks that require lifting of the arms above the head
  • Cachexia
  • EMG abnormality
  • Abnormality of the cardiovascular system
  • Ankle contracture
  • Joint stiffness
  • Myopathy

Muscles used for breathing are not affected much by this disease and thus, breathing problems are very rare. The heart muscle is also not generally affected.

As collagen type IV is found in the skin, symptoms of Bethlem myopathy are also seen on the skin. The outer surfaces of the arms and legs can feel dry or rough to touch. This is known as keratosis pilaris. Some may discover that they scar in an unusual manner. They may find that the scars either form keloids, which are raised and rather angry looking scars, or they may also have thin, silvery 'cigarette-like' paper scars.

Other symptoms of Bethlem myopathy mild weakness in the proximal and extensor muscles can give rise to limited functional impairment. Serum creatine kinase activity has been found to remain normal or slightly elevated. Muscle biopsy has shown non-specific myopathic changes in patients suffering from Bethlem myopathy. In children presenting with Bethlem myopathy, creatine kinase activity has been found to be highly elevated, sometimes even up to 15 times the upper limit of the normal value.

Diagnosis of Bethlem Myopathy

Diagnosis of Bethlem myopathy is generally suspected from medical history and a physical examination. The actual diagnosis is carried out by looking at a particular muscle set or skin through muscle and skin biopsy.

A muscle biopsy involves taking a small piece of muscle, generally from the thigh. Before going ahead with a muscle biopsy, some other tests may also be carried out that help in diagnosis of Bethlem myopathy. These include a blood test that measures the level of the protein creatine kinase (CK). In individuals suffering from Bethlem myopathy, the level of creatine kinase is only slightly elevated.

Muscle ultrasound can also detect changes in the muscle and provide an indication of the overall muscle condition. An ultrasound can provide further evidence of the extent of muscle involvement.

Muscle biopsy is a way of reaching a precise diagnosis. This can be done in the following ways:

Signs and symptoms that may indicate a muscle condition can be observed under a microscope. Muscle fibers of people suffering from muscular dystrophy will not be evenly sized and some of these fibers may also be replaced by fibrous tissue and/or fat.

A biopsy makes it possible to assess the amount of collagen type IV protein that is present in the muscle. This can be seen under the microscope using specific stains to highlight the presence of this protein.

Skin biopsy may also help in the diagnosis of Bethlem myopathy as collagen type IV is usually present in both muscle and skin. In many cases, it becomes easier to detect a reduction of the collagen IV protein by looking at skin cells rather than muscle cells. However, a skin biopsy cannot provide some of the information that a muscle biopsy can and therefore, most doctors prefer to conduct both muscle and skin biopsies to obtain the correct information required for diagnosis.

Genetic tests that look for abnormalities in one of the three genes in which mutation leads to Bethlem myopathy are also available now and can also provide a clear diagnosis.

Other tests that aid in the diagnosis of Bethlem myopathy include:

  1. Electromyography (EMG)
  2. Nerve conduction velocity (NCV)

Treatment of Bethlem Myopathy

There is specific treatment of Bethlem myopathy. There are only ways to alleviate the effects of the condition and prevent any further complications. Medications based on the severity, may be given as treatment of Bethlem myopathy.

If you are going to a muscle clinic, then they will a close check on your joints and mobility. Together with your physiotherapy team, you can work to stretch tight joints and maintain the flexibility and suppleness of your muscles. Some people may also need surgery to release the Achilles tendon. This can help a person to stand and walk more easily.

Both children and adults suffering from Bethlem myopathy are advised to remain active and manage their weights as an important part of treatment of Bethlem myopathy. Being overweight will further increase the strain on the muscles. Therapeutic exercises, physical therapy, proper nutrition and adequate sleep can aid in muscle repair, which can help relieve some symptoms of Bethlem myopathy.

Written, Edited or Reviewed By:

, MD, FFARCSI

Last Modified On: November 29, 2017

Pain Assist Inc.

Pramod Kerkar
  Note: Information provided is not a substitute for physician, hospital or any form of medical care. Examination and Investigation is necessary for correct diagnosis.

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