What are the other Names for this Condition? (Also known as/Synonyms)

• Benign Congenital Muscular Dystrophy
• Benign Congenital Myopathy with Contractures

What is Bethlem Myopathy? (Definition/Background Information)

• Bethlem Myopathy is a rare disorder affecting the skeletal muscles and connective tissue. The disorder is characterized by progressive muscle weakness and joint stiffness (contractures) in the fingers, wrists, elbows, and ankles
• 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 disorder may be inherited in an autosomal recessive manner
• Diagnosis is based on clinical examination and laboratory tests. Genetic testing may be used to confirm the diagnosis
• Treatment depends on individual symptoms but routinely involves physical therapy. Surgery to correct joint contractures may be undertaken as needed

(Source: Bethlem Myopathy; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Bethlem Myopathy? (Age and Sex Distribution)

• Bethlem Myopathy is a rare congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Bethlem Myopathy? (Predisposing Factors)

• A positive family history may be an important risk factor, since Bethlem Myopathy is an inherited condition
• Currently, no other risk factors have been clearly identified for the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Bethlem Myopathy? (Etiology)

• 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

(Source: Bethlem Myopathy; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Bethlem Myopathy?

The signs and symptoms of Bethlem Myopathy may include:

• Abnormality of the cardiovascular system
• Ankle contracture
• Congenital muscular torticollis
• Decreased fetal movement
• Distal muscle weakness
• Elbow flexion contracture
• Elevated serum creatine phosphokinase
• Limb-girdle muscle weakness   
• Motor delay
• Neonatal hypotonia
• Proximal muscle weakness
• Respiratory insufficiency due to muscle weakness
• Skeletal muscle atrophy
• Torticollis

Based on the frequency of symptoms observed, the following information may be noted: (Very frequently present symptoms in 80-99% of the cases)

• Cachexia
• Camptodactyly of finger
• EMG abnormality
• Joint stiffness
• Myopathy

(Source: Bethlem Myopathy; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Bethlem Myopathy Diagnosed?

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:

• Blood test measuring creatine kinase (CK) levels: These levels will typically be normal or only slightly elevated
• Skin biopsy
• Muscle MRI
• Electromyography (EMG)

Genetic testing of the COL6A1, COL6A2, and COL6A3 genes can confirm the diagnosis.

(Source: Bethlem Myopathy; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Bethlem Myopathy?

The complications of Bethlem Myopathy may include:

• Severe malnourishment
• Respiratory distress

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Bethlem Myopathy Treated?

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 disorder, 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

(Source: Bethlem Myopathy; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Bethlem Myopathy be Prevented?

• Currently, Bethlem Myopathy may not be preventable, since it is a genetic disorder
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Bethlem Myopathy? (Outcomes/Resolutions)

• The prognosis of Bethlem Myopathy is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Bethlem Myopathy:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/