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Disease Profile

Limb-girdle muscular dystrophy type 2B

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Adolescent

ICD-10

G71.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

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

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases; Nervous System Diseases

Summary

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. Specifically, LGMD2B is a slowly progressive disease that causes muscle weakness and wasting (atrophy) of the pelvic muscles and muscles of the shoulder girdle.[1] People who are Jewish, and specifically those of Libyan Jewish descent, are more likely to have LGMD2B.[2]

LGMD2B is caused by variations (also known mutations) in the DYSF gene. The disease is inherited in an autosomal recessive manner. Diagnosis of LGMD2B is suspected in people who have signs and symptoms of the disease, and the diagnosis can be confirmed by a muscle biopsy and genetic testing. While there are no treatments that can reverse the muscle weakness associated with the disease, supportive treatment can decrease complications.[1]

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.[2] The disease is slowly progressive, meaning the muscle weakness typically worsens over many years.[1]

The symptoms of LGMD2B typically begin in adolescence or young adulthood.[1] The age of onset ranges from 15 to 35 years, and the legs are usually the first part of the body affected.[3] 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.[2][4] The signs and symptoms of people with LGMD2B can vary, even among members of the same family.[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Elevated serum creatine kinase
Elevated blood creatine phosphokinase
Elevated circulating creatine phosphokinase
Elevated creatine kinase
Elevated serum CPK
Elevated serum creatine phosphokinase
High serum creatine kinase
Increased CPK
Increased creatine kinase
Increased creatine phosphokinase
Increased serum CK
Increased serum creatine kinase
Increased serum creatine phosphokinase

[ more ]

0003236
30%-79% of people have these symptoms
Lower limb muscle weakness
Lower extremity weakness
Lower limb weakness
Muscle weakness in lower limbs

[ more ]

0007340
Proximal muscle weakness in lower limbs
0008994
5%-29% of people have these symptoms
Abnormal EKG
Abnormal ECG
0003115
Calf muscle hypertrophy
Increased size of calf muscles
0008981
Cardiomegaly
Enlarged heart
Increased heart size

[ more ]

0001640
Difficulty climbing stairs
Difficulty walking up stairs
0003551
Difficulty running
0009046
Hyperlordosis
Prominent swayback
0003307
Muscular edema
0100748
Neck flexor weakness
Neck flexion weakness
0003722
Pes cavus
High-arched foot
0001761
Proximal muscle weakness in upper limbs
0008997
Reduced ejection fraction
0012664
Reduced tendon reflexes
0001315
Right bundle branch block
0011712
Right ventricular hypertrophy
0001667
Scapular winging
Winged shoulder blade
0003691
1%-4% of people have these symptoms
Brachial plexus neuropathy
0045054
Chorea
0002072
Distal upper limb muscle weakness
0008959
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Inability to walk
0002540
Limited elbow movement
Decreased elbow mobility
Limited elbow mobility
Restricted elbow motion

[ more ]

0002996
Limited hip movement
0008800
Limited knee flexion/extension
0005085
Pollakisuria
Frequent urination
0100515
Spinal rigidity
Reduced spine movement
0003306
Tip-toe gait
Walking on tiptoes
0030051
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
EMG: myopathic abnormalities
0003458
Fatigue
Tired
Tiredness

[ more ]

0012378
Increased connective tissue
0009025
Increased variability in muscle fiber diameter
0003557
Muscle fiber splitting
0003555
Muscular dystrophy
0003560
Proximal muscle weakness
Weakness in muscles of upper arms and upper legs
0003701
Slow progression
Signs and symptoms worsen slowly with time
0003677

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. 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.[1][2]

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:[1]

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.[1]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
  • The Jain Foundation sponsors genetic testing to confirm the diagnosis of dysferlinopathy.

    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:[1]

    • 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.[5]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
        • Genetics Home Reference (GHR) contains information on Limb-girdle muscular dystrophy type 2B. This website is maintained by the National Library of Medicine.
        • Muscular Dystrophy Association has information and resources about Limb-girdle muscular dystrophy type 2B. Please click on the link to access this resource.
        • The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Limb-girdle muscular dystrophy type 2B. Click on the link to view a sample search on this topic.

            References

            1. Aoki M. Dysferlinopathy. GeneReviews. March 5, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1303/.
            2. Pegoraro E and Hoffman EP. Limb-Girdle Muscular Dystrophy Overview. GeneReviews. August 30, 2012; https://www.ncbi.nlm.nih.gov/books/NBK1408/.
            3. Basil T Darras. Limb-girdle muscular dystrophy. UpToDate. Waltham, MA: UpToDate; February, 2016;
            4. Autosomal recessive limb-girdle muscular dystrophy type 2B. Orphanet. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=268. Accessed 12/17/2017.
            5. Limb-Girdle Muscular Dystrophy (LGMD). Muscular Dystrophy Association (MDA). https://www.mda.org/disease/limb-girdle-muscular-dystrophy. Accessed 12/17/2017.
            6. Glenn Lopate. Limb-Girdle Muscular Dystrophy. Medscape Reference. October 28, 2014; https://emedicine.medscape.com/article/1170911-overview.

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