Bethlem muscular dystrophy is an uncommon, inherited disorder that affects the body’s connective tissues and muscles, leading to gradual muscle weakening. It is a type of congenital muscular dystrophy.
Understanding Bethlem Muscular Dystrophy
Bethlem muscular dystrophy is categorized as a collagen VI-related dystrophy, a group of conditions stemming from issues with collagen type VI protein. This protein acts as a scaffold, providing structural support to muscle cells and their surrounding extracellular matrix. When the genes responsible for producing collagen VI are mutated, the protein may be faulty or insufficient, leading to destabilization of the extracellular matrix and subsequent muscle weakness and damage.
The genetic basis involves mutations in one of three genes: COL6A1, COL6A2, or COL6A3. These genes provide instructions for creating the alpha chains that form collagen VI. The disease follows an autosomal dominant inheritance pattern, meaning one mutated copy of the gene is sufficient to cause the condition. This results in a 50% chance for each child of an affected individual to inherit the pathogenic variant.
In rarer instances, Bethlem muscular dystrophy can exhibit an autosomal recessive inheritance pattern. This occurs when an individual inherits two mutated copies of a collagen VI-encoding gene, one from each parent. The parents usually carry one mutated copy but do not show symptoms.
Clinical features of Bethlem muscular dystrophy often become apparent in early childhood, though symptoms can emerge from birth through adulthood. Individuals experience progressive muscle weakness, affecting both proximal muscles (hips and shoulders) and distal muscles. This weakness can result in difficulties with actions such as lifting arms overhead, standing from a seated position, or climbing stairs.
A prominent characteristic of the condition is the development of joint contractures, which are areas of stiffness that limit the range of motion. These commonly affect the elbows, Achilles tendons, and long finger flexors, making fine motor skills challenging. Affected individuals may also exhibit characteristic skin changes, including follicular hyperkeratosis and atrophic scarring. Easy fatigue and poor stamina are also reported.
Diagnosis and Disease Course
The diagnostic process for Bethlem muscular dystrophy typically begins with a thorough clinical evaluation. Professionals assess a patient’s medical history, conduct a physical examination to identify muscle weakness patterns, and examine joint contractures. Muscle MRI can also suggest the diagnosis by showing specific muscle involvement patterns.
Muscle biopsy is another diagnostic tool. A small sample of muscle tissue is analyzed under a microscope, revealing characteristic dystrophic changes like degeneration, regeneration, and replacement of muscle with fat and fibrous tissue. Immunostaining can also assess collagen VI presence and localization, which may be absent or mislocalized in affected individuals.
Definitive diagnosis is achieved through molecular genetic testing, analyzing blood samples to identify variants in the COL6A1, COL6A2, or COL6A3 genes. This genetic confirmation is considered the gold standard. Genetic testing can also be used for prenatal diagnosis and preimplantation genetic testing if variants have been identified in an affected family member.
The disease course is generally slow and progressive. While symptoms can manifest in early childhood, individuals often maintain the ability to walk into adulthood. As the disease advances, mobility aid needs gradually increase. Over two-thirds of individuals over 50 years of age may require assistive devices for outdoor mobility, such as crutches, canes, or wheelchairs.
Respiratory involvement can occur in some patients, though it is often less severe or consistent compared to other muscular dystrophies. In adulthood, respiratory muscle weakness, particularly affecting the diaphragm, can lead to respiratory insufficiency, sometimes necessitating nocturnal non-invasive ventilation. The severity of muscle weakness and joint stiffness can vary significantly between individuals, even within the same family.
Managing Bethlem Muscular Dystrophy
As there is no cure, management strategies focus on supportive care aimed at alleviating symptoms and improving an individual’s quality of life. A multidisciplinary team approach involves various healthcare professionals to address diverse aspects of the condition. This team may include neurologists, physical therapists, occupational therapists, orthopedists, and pulmonologists.
Physical therapy plays a significant role in maintaining muscle strength and flexibility, and in preventing or minimizing joint contractures. Therapists design personalized exercise routines, including stretching and low-impact aerobic activities like swimming or walking. These interventions help preserve range of motion and can slow the progression of joint stiffness.
Occupational therapy assists individuals in adapting to changes in their physical abilities and performing daily living activities. Occupational therapists teach strategies and recommend adaptive devices to help with tasks like feeding, grooming, dressing, and workplace activities. They also provide guidance on the use of assistive devices for mobility and independence.
Pain management addresses discomfort from muscle weakness or joint issues. Orthopedic management may be necessary to address contractures, potentially involving splints or, in some cases, tendon release surgery for conditions like Achilles tendon contractures. Assistive devices, such as canes, walkers, wheelchairs, and orthotic devices like ankle-foot orthoses or wrist splints, are recommended to support mobility and joint stability.
For those with respiratory involvement, interventions like mechanical insufflator-exsufflators can promote airway clearance. Regular monitoring by a pulmonologist helps manage any breathing difficulties. Ongoing collaboration among healthcare professionals ensures care plans are adjusted as the disease progresses, providing comprehensive support tailored to the individual’s evolving needs.