Bethlem myopathy

Bethlem myopathy, or Bethlem muscular dystrophy, is a rare, progressive form of muscular dystrophy that primarily affects skeletal muscles and connective tissues. While the condition has not been associated with reduced lifespan, progressive declines in strength and joint mobility mean that patients older than 50 often require mobility aids such as crutches or wheelchairs outdoors.

Bethlem myopathy has been classified as a form of limb-girdle muscular dystrophy.

What is Bethlem myopathy?

Bethlem myopathy is a rare type of muscular dystrophy that affects skeletal muscles (attached directly to bones), connective tissues (ligaments and tendons), and the skin.

A study from northern England estimates that this very rare form of muscular dystrophy affects approximately 1 in 130,000 people.

What are the symptoms of Bethlem myopathy?

Bethlem myopathy symptoms can emerge at any age and vary widely among individuals. Signs may appear before birth when a fetus exhibits decreased movement in the womb.

Contractures of the last four fingers distinguish Bethlem myopathy from other forms of muscular dystrophy. Research also indicates that elbow contractures develop in more than half of all affected individuals. The condition commonly affects the fingers, wrists, elbows, and ankles.

Signs and symptoms include:

• waddling gait: A wobbling walk typically driven by hip and thigh weakness
• spinal issues: Difficulty bending the neck or back due to stiffness or abnormal curvature of the spine
• protruding shoulder blades: Winged shoulder blades that stick out prominently
• abnormal muscle cells: Biopsies showing small, clear gaps or holes within muscle cells
• follicular keratosis: Rough, tiny bumps appearing on the upper arms and thighs
• hyperflexible joints: Joints moving beyond their normal range of motion
• hyperkeratosis: Thickening of the skin’s outer layer
• difficulty standing: Needing to push off legs with hands to stand up due to weak hip and thigh muscles
• general muscle wasting: Widespread loss of muscle tissue
• foot drop: Weakness lifting the front part of the foot, leading to difficulty walking
• stiff, bent elbows: Elbow joints stuck in a bent position that cannot fully straighten
• curved toe bones: Deformed or bent toe bones
• central muscle weakness: Reduced strength in the head, neck, and trunk
• tight Achilles tendon: Shortened or tight tendons connecting calves to heels
• respiratory system issues: Problems involving the airways, lungs, or breathing muscles can occur, but are not a consistent symptom

Children with Bethlem myopathy frequently exhibit hypotonia (low muscle tone) and torticollis (wryneck). These children usually experience delayed motor development, learning to sit or walk later than expected. Progressive muscle weakness and contractures may also appear later in adulthood.

Individuals or parents observing muscle weakness, unusual clumsiness, frequent falls, or developmental delays should consult a physician. Early evaluation helps distinguish Bethlem myopathy from other neuromuscular conditions.

Causes

Mutations in any of three collagen type VI-encoding genes cause the condition: COL6A1, COL6A2, or COL6A3. Each gene produces a component of collagen type VI, an essential structural protein within the extracellular matrix (ECM) of skeletal muscle and other tissues. This form of collagen helps provide structural support by forming a mesh-like structure between cells.

Gene mutations result in abnormal or insufficient collagen type VI. This deficiency weakens structural ECM support, leading to progressive muscle weakness and joint contractures. Over time, these cellular changes produce collagen-VI-related dystrophies such as Bethlem myopathy.

Bethlem myopathy inheritance

Bethlem myopathy inheritance typically follows an autosomal dominant pattern, meaning an individual needs to inherit only one altered COL6A1, COL6A2, or COL6A3 gene from one parent to develop the condition.

In rare cases, the condition follows an autosomal recessive pattern requiring two altered gene copies — one from each parent. Some individuals develop the condition spontaneously without any family history.

Diagnosis

Reaching a diagnosis of Bethlem myopathy often requires time, averaging more than six years. Because of its rarity, primary care physicians may be unfamiliar with the condition, necessitating referrals to specialists or second opinions.

Physicians suspect Bethlem myopathy based on clinical findings and medical history, and confirm the diagnosis with specialized testing. Patients are typically referred to a neurologist for a detailed evaluation. Diagnostic approaches include:

• muscle biopsy: Usually taken from the thigh, a biopsy evaluates structural changes and measures collagen type VI production levels.
• muscle MRI: Imaging helps identify structural collagen-VI changes within muscle tissue and connective tissue.
• electromyography: Measures electrical activity in muscles to assess muscle health and function.
• genetic testing: Analyzing the COL6A1, COL6A2, and COL6A3 genes. This can confirm the presence of mutations that cause Bethlem myopathy.

Genetic testing, often using a myopathy gene panel that includes COL6A analysis, is generally the preferred first test because it can provide the most specific diagnosis. Some panels are available at no cost, and results typically take a few weeks.

Treatments

No cure currently exists, but Bethlem myopathy treatment options can effectively manage symptoms and improve daily quality of life.

Physical therapy, occupational therapy, and structured exercise help maintain joint flexibility, range of motion, and physical independence. Therapists also provide guidance on mobility devices when required.

Surgical intervention may help release severe contractures, improving hand function, standing, and walking. Scoliosis may also require corrective spine surgery. Surgical candidates must discuss anesthesia, post-operative care, and rehabilitation thoroughly with their surgical team, as neuromuscular patients require specialized respiratory monitoring and cautious anesthesia management.

Patients 50 and older often rely on canes, crutches, or wheelchairs. Some individuals require nighttime ventilation support, making routine lung evaluations essential for tracking respiratory function.

How does Bethlem myopathy progress?

Disease onset varies considerably. Some individuals exhibit signs from birth — including detectable intrauterine changes on prebirth scans — while others develop symptoms in adulthood. Progression is typically slow across all age groups.

Individuals with early onset usually walk unassisted until early adulthood. By age 50, approximately two-thirds of patients require walking assistance outdoors. Respiratory surveillance remains important because breathing complications can develop in later stages.

Living with Bethlem myopathy

Bethlem myopathy presents challenges with daily routines. Tasks such as raising arms overhead, standing from a chair, climbing stairs, or brushing teeth may grow difficult as fine motor skills and physical strength diminish. Getting tired easily is also common.

Physical therapists recommend mild-to-moderate exercises, such as swimming, stretching, aquatherapy, and walking, to slow the progression of contractures. Annual flu vaccinations are recommended to prevent chest infections that exacerbate underlying lung vulnerabilities. Patients using nighttime ventilation should also discuss receiving the pneumococcal vaccine with their physician.

Under the Americans with Disabilities Act (ADA), qualifying employers (15 or more employees) must offer reasonable workplace accommodations. Helpful accommodations include:

• desk footrests
• accessible parking spaces
• scheduled rest breaks
• remote work options

Bethlem myopathy’s life expectancy appears to be normal. Patients should maintain open communication with healthcare providers to monitor disease progression and proactively manage potential respiratory complications.

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