Limb-girdle muscular dystrophy type 2B

Alternate names

LGMD2B; Muscular dystrophy, limb-girdle, type 3; LGMD3

Definition

Limb-girdle muscular dystrophy type 2B (LGMD2B) is one type of limb-girdle muscular dystrophy. These diseases affect the voluntary muscles, which are the muscles that are moved on purpose, such as the arms, legs, fingers, toes, and facial muscles.

Epidemiology

• Several studies throughout the world have estimated the frequency of LGMDs. Different populations often have different frequencies of the various LGMDs. The overall frequency of all LGMDs has been estimated to be 5-70 people per 1 million in several countries.
• This is approximately 1 in 14,286 to 1 in 200,000.
• Some have estimated a slightly smaller prevalence range, from 1 in 14,500 to 1 in 123,000 people.
• LGMD2B is thought to account for 3-19% of all LGMDs.
• In many studies, LGMD2A is the most common (accounting for 8-26% of all LGMDs).

Cause

• Limb-girdle muscular dystrophy type 2B (LGMD2B) is caused by changes to the DYSF gene.
• When a genetic change causes a disease, it is also known as a pathogenic variation.
• The DYSF gene provides instructions to make a protein called dysferlin.
• Dysferlin is found in the thin membrane (sarcolemma) that surrounds muscle fibers.
• Scientists believe dysferlin is involved in repairing muscle fibers damaged naturally through use and may also be involved in the control of muscle inflammation.

Gene mutations

• When there is a pathogenic mutation in the DYSF gene, the instructions to make dysferlin are not correct, which means the protein is either not made at all or the protein that is made cannot do its job properly.
• Without working dysferlin, the muscles are not able to repair themselves correctly and may become inflamed too easily leading to further damage to the muscle.
• Over time, this leads to the muscle weakness and wasting associated with LGMD2B.

Inheritance

Autosomal recessive inheritance, a 25% chance

Limb-girdle muscular dystrophy type 2B (LGMD2B), and all subtypes of LGMD type 2, are inherited in an autosomal recessive manner.

This means that people with LGMD2B have pathogenic variations (changes, formerly known as mutations) in both copies of the DYSF gene in each cell of the body. We inherit one copy of each gene from our mother and the other from our father. People who have only one changed copy of the DYSF gene are known as carriers of the disease. Carriers of LGMD2B typically do not have any signs or symptoms of the disease. When two carriers of LGMD2B have children, each child has a:

• 25% chance to have LGMD2B
• 50% chance to be a carrier of LGMD2B like each parent
• 25% chance to have inherited two working copies of the DYSF gene, so he or she is not a carrier and is not affected with the disease

Onset

The symptoms of LGMD2B typically begin in adolescence or young adulthood. The age of onset ranges from 15 to 35 years, and the legs are usually the first part of the body affected.

Signs and symptoms

• Limb-girdle muscular dystrophy type 2B (LGMD2B) causes muscle weakness and wasting (atrophy) of the muscles of the pelvis and shoulder girdle.
• The muscle weakness can cause an inability to tiptoe and difficulty walking and running.
• In some cases, people with the disease may have enlarged (hypertrophic) calf muscles.
• The disease is slowly progressive, meaning the muscle weakness typically worsens over many years.
• Symptoms that may be common in other types of limb-girdle muscular dystrophy, such as heart (cardiac) and breathing (respiratory) problems, are uncommon in people with LGMD2B.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Elevated serum creatine kinase(Elevated blood creatine phosphokinase)

30%-79% of people have these symptoms

• Lower limb muscle weakness(Lower extremity weakness)
• Proximal muscle weakness in lower limbs

5%-29% of people have these symptoms

• Abnormal EKG(Abnormal ECG)
• Calf muscle hypertrophy(Increased size of calf muscles)
• Cardiomegaly(Enlarged heart)
• Difficulty climbing stairs(Difficulty walking up stairs)
• Difficulty running
• Hyperlordosis(Prominent swayback)
• Muscular edema
• Neck flexor weakness(Neck flexion weakness)
• Pes cavus(High-arched foot)
• Proximal muscle weakness in upper limbs
• Reduced ejection fraction
• Reduced tendon reflexes
• Right bundle branch block
• Right ventricular hypertrophy
• Scapular winging(Winged shoulder blade)

1%-4% of people have these symptoms

• Brachial plexus neuropathy
• Chorea
• Distal upper limb muscle weakness
• Dysphagia(Poor swallowing)
• Inability to walk
• Limited elbow movement(Decreased elbow mobility)
• Limited hip movement
• Limited knee flexion/extension
• Pollakisuria(Frequent urination)
• Spinal rigidity(Reduced spine movement)
• Tip-toe gait(Walking on tiptoes)

Diagnosis

• Limb-girdle muscular dystrophy (LGMD) is typically suspected when a person develops muscle weakness and wasting in the legs and arms, usually in the areas closest to the hips and shoulders, but not elsewhere in the body.
• However, it is hard to diagnose which type of LGMD a person may have without further testing.
• The doctor may wish to take a thorough personal and family history and to run some laboratory tests.

These tests may include:

• Electromyography (EMG)
• Creatine-kinase levels
• Muscle biopsy
• Immunoblotting to determine if the dysferlin protein is present at typical levels
• Genetic testing of the DYSF gene may be ordered to confirm the diagnosis of LGMD2B and to help identify family members who are carriers of the disease.

Treatment

Unfortunately, there is no cure for limb-girdle muscular dystrophy type 2B (LGMD2B).

Treatment options that may be recommended for people with LGMD2B may include:

• Weight control to avoid obesity
• Physical therapy and stretching exercises
• Use of mechanical aids such as canes, walkers, and wheelchairs
• It is recommended that people with LGMD2B be provided with social and emotional support to cope with the diagnosis.
• Other specialists that may be recommended include a neurologist, occupational therapist, nutritionist, and genetic counselor.
• No currently available medications can relieve or reverse the symptoms associated with LGMD2B.
• However, research is ongoing to try to determine if treatments such as gene therapy may be helpful in the future.

Prognosis

• In general, limb-girdle muscular dystrophy type 2B (LGMD2B) is a slowly progressive disease, meaning the muscle weakness slowly continues to worsen. Eventually, most people with LGMD2B require a wheelchair, but this may be years after the diagnosis.
• Muscle weakness affecting the heart muscles or muscles necessary for breathing is uncommon in people with LGMD2B.
• In rare cases, the progression of the disease may be more rapid, with people requiring a wheelchair in one or two years after symptoms begin.

NIH genetic and rare disease info

• NIH info on Limb-girdle muscular dystrophy type 2B

Limb-girdle muscular dystrophy type 2B is a rare disease.

Limb-girdle muscular dystrophy type 2B Resources
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