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Limb-girdle muscular dystrophy type 2B (Miyoshi)
LGMD2B primarily affects muscles around the hips and shoulders, but can also involve muscles in the lower legs. It is a progressive condition, meaning symptoms tend to worsen over time, and typically appears in late adolescence or early adulthood.
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Overview
Limb-girdle muscular dystrophy type 2B (LGMD2B), also known as Miyoshi myopathy, is a form of muscular dystrophy that causes gradual weakening and wasting of muscles. This condition is part of a larger group of disorders called limb-girdle muscular dystrophies, which are categorised by the primary muscles affected - those around the shoulders and hips (the 'limb girdles'). LGMD2B specifically impacts how muscle cells repair themselves after everyday strain.
This condition typically begins in late adolescence or early adulthood, though the age of onset can vary [PMID:19363098]. Over time, the muscle weakness can affect mobility, making activities like climbing stairs or lifting objects challenging. The progression and severity of LGMD2B can differ significantly between individuals, even within the same family.
Symptoms & clinical features
The main symptom of LGMD2B is progressive muscle weakness. This weakness often starts in muscles closer to the body's centre, such as those in the hips, thighs, and buttocks. This can lead to difficulty with activities like running, climbing stairs, or rising from a seated position. Over time, the weakness may spread to muscles in the shoulders and upper arms, making it harder to lift objects or reach overhead.
In some individuals, the initial symptoms of LGMD2B may appear in the muscles of the lower legs, particularly the calves, a presentation sometimes referred to as Miyoshi myopathy. This can lead to difficulty walking on heels or toes. Muscle pain and cramps can also be experienced by some individuals. As the condition advances, mobility may become increasingly challenging, and some people may eventually require mobility aids.
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Affected organs
LGMD2B primarily affects the skeletal muscles, which are the voluntary muscles responsible for movement. The muscles most commonly involved are those of the pelvic girdle (hips, upper thighs, buttocks) and the shoulder girdle (shoulders, upper arms). In some cases, muscles in the lower legs are affected early in the disease course.
While LGMD2B is predominantly a skeletal muscle disorder, there is some research suggesting potential, though less common, involvement of other systems. However, significant cardiac or respiratory muscle involvement, which can be a feature of some other muscular dystrophies, is generally not a prominent characteristic of LGMD2B [PMID:19363098].
Risks & severity
The severity of LGMD2B can vary widely among affected individuals. Symptoms typically begin in late adolescence or early adulthood, but onset can range from early childhood to later adulthood. The rate at which muscle weakness progresses also differs; some individuals experience a slow decline over decades, while others may have a more rapid progression [PMID:24263073].
While LGMD2B generally progresses to affect mobility, the degree of impact on daily life varies. Many individuals maintain the ability to walk for several decades after symptom onset. However, some may eventually require the use of walking aids or a wheelchair. Life expectancy is generally not significantly affected by LGMD2B itself, as severe cardiac or respiratory complications are uncommon.
Genetic causes
Limb-girdle muscular dystrophy type 2B is caused by pathogenic variants in the DYSF gene. This gene provides instructions for making a protein called dysferlin. Dysferlin is primarily found in the sarcolemma, which is the membrane that surrounds muscle fibres.
The dysferlin protein plays a crucial role in repairing muscle damage that occurs during normal muscle activity. It helps to mend tiny tears in the sarcolemma, preventing further damage to the muscle cell. Pathogenic variants in DYSF lead to the production of a non-functional or absent dysferlin protein. Without proper dysferlin, muscle cells are less efficient at repairing themselves, leading to a build-up of damage and eventual muscle weakness and wasting [PMID:24263073].
- DYSF dysferlinThe DYSF gene provides instructions for producing the dysferlin protein, which is critical for muscle fibre repair and maintaining muscle integrity.
Inheritance pattern
LGMD2B is inherited in an autosomal recessive pattern. This means that an individual must inherit two altered copies of the DYSF gene (one from each parent) to develop the condition. If a person inherits only one altered copy of the DYSF gene, they are considered a 'carrier' and typically do not show symptoms of LGMD2B.
When both parents are carriers of a pathogenic variant in the DYSF gene, there is a 25% chance with each pregnancy that their child will inherit two altered copies and be affected by LGMD2B. There is a 50% chance the child will be a carrier, and a 25% chance the child will inherit two unaffected copies of the gene and not be a carrier or affected. Genetic counselling can provide detailed information about inheritance patterns and risks for family members.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
The diagnosis of LGMD2B often begins with a clinical examination by a neurologist, who will assess muscle weakness patterns. Blood tests may show elevated levels of creatine kinase (CK), an enzyme released when muscles are damaged. Muscle biopsy, where a small sample of muscle tissue is taken, can reveal characteristic changes and a lack of dysferlin protein, which can help support a diagnosis.
A definitive diagnosis of LGMD2B is confirmed through genetic testing, which looks for pathogenic variants in the DYSF gene. In the UK, genetic testing for muscular dystrophies like LGMD2B is available through the NHS Genomic Medicine Service. A clinical geneticist or neurologist would typically refer individuals for such testing. The relevant NHS Genomic Medicine Service R-code for limb-girdle muscular dystrophies, including LGMD2B, is R83.
Management & lifestyle
While there is currently no cure for LGMD2B, management focuses on alleviating symptoms, maintaining muscle function, and improving quality of life. Physiotherapy can be very beneficial, involving exercises to maintain muscle strength, flexibility, and mobility. Occupational therapy can help individuals adapt to daily tasks and suggest assistive devices as needed.
The NHS provides comprehensive care pathways for individuals with neuromuscular conditions. This typically involves regular follow-up with a neurologist, physiotherapist, and other specialists as required. Lifestyle adjustments, such as maintaining a healthy weight and avoiding excessive muscle strain, may also be recommended. Research into potential therapies for LGMD2B is ongoing, providing hope for future treatments.
UK care pathway
In the UK, individuals suspected of having genetic conditions like LGMD2B are typically referred to a clinical genetics service or a specialist neuromuscular centre. These services can arrange for genetic testing through the NHS Genomic Medicine Service, often using specific R-codes like R83 for limb-girdle muscular dystrophies. A genetic counsellor will provide support and information regarding the genetic diagnosis, inheritance patterns, and implications for family members. Multidisciplinary teams, including neurologists, physiotherapists, and occupational therapists, work together to provide ongoing care and management.
Frequently asked questions
What is the typical age that LGMD2B symptoms start?
Symptoms of LGMD2B most commonly begin in late adolescence or early adulthood, generally between the ages of 15 and 30. However, there can be variation, with some individuals experiencing symptoms earlier or later in life.
Does LGMD2B affect the heart or breathing?
Unlike some other forms of muscular dystrophy, significant heart or breathing problems are generally not a common feature of LGMD2B. The condition primarily affects the skeletal muscles responsible for movement.
Can LGMD2B be passed down to children?
Yes, LGMD2B is inherited in an autosomal recessive pattern. This means that if both parents are carriers of a pathogenic DYSF gene variant, there is a 25% chance with each pregnancy that their child will inherit two altered copies and be affected by the condition.
Is there a cure for LGMD2B?
Currently, there is no cure for LGMD2B. Management focuses on supportive care, such as physiotherapy and occupational therapy, to help manage symptoms and maintain muscle function. Research into potential new treatments is ongoing.
Will I eventually need a wheelchair if I have LGMD2B?
The progression of LGMD2B varies greatly among individuals. While some people may eventually require mobility aids or a wheelchair, many maintain the ability to walk for several decades after their symptoms begin. Your care team can provide more personalised information.