Limb-Girdle Muscular Dystrophy (LGMD)

What is Limb-Girdle Muscular Dystrophy (LGMD)?

 
An illustration of two muscle cells are side by side. One shows a healthy muscle cell, which larger and fuller, next to an atrophied muscle cell, which looks narrow and smaller. Beside those is an illustration of the muscles of the human body.

Limb-Girdle Muscular Dystrophy (LGMD) is a rare, genetic neuromuscular disorder with over 33 different sub-types, including many forms without an identified genetic cause (1, 2, 3). Between all of the different subtypes, it is estimated that about 2 out of every 100,000 people in the United States is born with LGMD (1, 2).

The condition causes muscle weakness and muscle loss in different parts of the body, predominantly those in the limb-girdle regions, which are the areas of the body around the bones of the shoulders and pelvis (1). Muscle loss in these regions can cause weakness surrounding the shoulders, upper arms, upper legs, and hips.  The severity varies depending on which type of LGMD an individual has. LGMD often creates complications with the heart muscles, muscles used for breathing, and muscles used for swallowing that affect their functioning. Weakness in other areas of the body is also a common symptom.

Progression of LGMD can vary between types. Some forms of LGMD begin to show symptoms from as early as infancy, others as late as adulthood. The first outward signs may be difficulty with walking that appears as a waddling gait. This is caused by early muscle changes in the hips and legs (3, 4).

All forms of LGMD are caused by an identified or unknown genetic change. These specific genetic changes are generally how subtypes of the condition are classified. Knowing which genetic change causes a person’s LGMD is important to predicting the condition's progression, identifying additional complications, and finding appropriate treatments and clinical trials (1, 2, 4).

 
 

What are some of the different forms of LGMD?

LGMD subtypes are first classified by their observed inheritance pattern. Due to the rapidly growing identification of new subtypes of LGMD, the naming of each disorder was updated in 2017. Dominant forms of LGMD are now specified as “LGMD D#” and the recessive forms are designated as “LGMD R#,” where the “#” represents when the genetic cause for each disorder was identified in relation to the others in chronological order. For example, “LGMD R1” would mean it was the first recessive form identified, and R24  would be one of the newest ones identified. However, it often takes time for clinicians and patients to adjust to new classifications and names. Some of the older names are still used widely today (10).

Autosomal dominant forms of LGMD are caused by a single copy of a genetic change that is either inherited from one parent or caused by a new genetic change during conception. Those diagnosed with an autosomal dominant form of LGMD have a 50% chance of passing the genetic change on to their naturally conceived children (2). Autosomal dominant forms of LGMD were originally classified as LGMD Type 1 and are currently classified as LGMD D Group (1, 4).

Autosomal dominant disorders formerly classified as LGMD before the 2018 reclassification:

  • Two forms of Myofibrillar Myopathy were formerly classified as LGMD1A and LGMD1E (9, 11, 13)

  • Emery-Dreifuss Muscular Dystrophy was formerly classified as LGMD1B, also called nuclear envelopathy (9, 13)

  • Rippling Muscle Disease was formerly classified as LGMD1C, also called caveolae-associated muscular dystrophy (9, 13)

Some examples of LGMD Type 1 or LGMD D Group include:

  • LGMDD1 also called LGMD D1 DNAJB6-related

    • Formerly LGMD1D (1, 9, 13)

  • LGMDD2 also called LGMD D2 TNP03-related, and nuclear envelopathy

    • Formerly LGMD1F (1, 9, 11, 13)

  • LGMDD3 also called LGMD D3 HNRNPDL-related

    • Formerly LGMD1G (1, 9, 13)

  • LGMDD4 also called LGMD D4 calpain3-related

    • Formerly LGMD1H (3, 9, 12, 13)

  • LGMDD5 also called LGMD D5 collagen 6-related

    • Formerly called Bethlem Myopathy Dominant (13)


Autosomal recessive forms of LGMD occur when each parent carries a genetic change that causes the disease only when a person has two copies of the change. The most common forms of LGMD are those with an autosomal recessive inheritance pattern. For these cases, the individual inherits an altered gene copy from each of their parents. In these instances, two parents who are carriers of autosomal recessive LGMD have a 25% chance of having an affected child, a 25% chance of having an unaffected child that does not carry the genes, and a 50% chance of having an unaffected child that carries a single copy of the genetic change themselves (1). They were originally classified as LGMD Type 2 and are currently classified by LGMD R Group (1, 4).

Autosomal recessive disorders formerly classified as LGMD before the 2018 reclassification:

  • Pompe Disease

    • Formerly LGMD2V (3, 9, 13)

  • Myofibrillar Myopathy or z-disk proteinopathy

    • Formerly LGMD2R (3, 9, 13)

  • PINCH-2-related Myopathy

    • Formerly LGMD2W (3, 9, 13)

  • BVES-related myopathy or nuclear envelopathy

    • Formerly LGMD2X (3, 9, 13)

  • TOR1AIP1-related Myopathy or nuclear envelopathy

    • Formerly LGMD2Y(3, 9, 13)

Some examples of LGMD Type 2 or LGMD R Group include:

  • LGMDR1 also called LGMD R1 calpain3-related, and calpain-deficient LGMD

    • Formerly LGMD2A (1, 2, 3, 13)

  • LGMDR2 also called LGMD R2 dysferlin-related

    • Formerly LGMD2B(1, 2, 3, 13)

  • LGMDR3 also called LGMD R3 alpha-sarcoglycan-related

    • Formerly LGMD2D (1, 2, 3, 13)

  • LGMDR4 also called LGMD R4 beta-sarcoglycan-related

    • Formerly LGMD2E (1, 2, 3, 13)

  • LGMDR5 also called LGMD R5 gamma-sarcoglycan related 

    • Formerly LGMD2C (1, 2, 3, 13)

  • LGMDR6 also called LGMD R6 delta-sarcoglycan-related

    • Formerly LGMD2F (1, 2, 3, 13)

  • LGMDR7 also called LGMD R7 telethonin-related

    • Formerly LGMD2G (1, 2, 3, 13)

  • LGMDR8 also called LGMD R8 TRIM32-related

    • Formerly LGMD2H (1, 2, 3, 13)

  • LGMDR9 also called LGMD R9 FKRP-related, or Fukutin-related proteinopathy

    • Formerly LGMD2I (1, 2, 3, 5, 13)

  • LGMDR10 also called LGMD R10 titin-related

    • Formerly LGMD2J (1, 2, 3, 13)

  • LGMDR11 also called LGMD R11 POMT1-related

    • Formerly LGMD2K (1, 2, 3, 5, 13)

  • LGMDR12 also called LGMD R12 anoctamin5-related

    • Formerly LGMD2L (1, 2, 3, 13)

  • LGMDR13 also called LGMD R13 Fukutin-related

    • Formerly LGMD2M (1, 2, 3, 5, 13)

  • LGMDR14 also called LGMD R14 POMT2-related

    • Formerly LGMD2N (1, 2, 3, 5, 13)

  • LGMDR15 also called LGMD R15 POMGnT1-related

    • Formerly LGMD2O (1, 2, 3, 5, 13)

  • LGMDR16 also called LGMD R16 a-dystroglycan-related

    • Formerly LGMD2P (1, 2, 3, 5, 13)

  • LGMDR17 also called LGMD R17 plectin-related or z-disk proteinopathy

    • Formerly LGMD2Q (3, 9, 13)

  • LGMDR18 also called LGMD R18 TRAPPC11-related or alpha-dystroglycanopathy (6, 7, 9, 13)

    • Formerly LGMD2S

  • LGMDR19 also called LGMD R19 GMPPB-related

    • Formerly LGMD2T (1, 2, 3, 5, 13)

  • LGMDR20 also called LGMD R20 ISPD-related

    • Formerly LGMD2U (1, 2, 3, 5, 13)

  • LGMD21 also called LGMD R21 POGLUT1-related

    • Formerly LGMD2Z (8, 9, 13)

  • LGMDR22 also called LGMD R22 collagen 6-related

    • Formerly Bethlemm Myopathy Recessive (13)

  • LGMDR23 also called LGMD R23 Laminin alpha-2-related

    • Formerly Laminin alpha-2-related Muscular Dystrophy (13)

  • LGMDR24 also called LGMD R24 POMGNT2-related

    • Formerly POMGNT2-related Muscular Dystrophy (13)

 

How is it Diagnosed?

A provider can diagnose LGMD in several ways. The first step is generally a physical examination. A provider would aim to identify the specific presenting symptoms to consider if they could be part of a syndrome. During or after the physical examination, the provider will likely order a creatine kinase (CK) blood test to determine if there is active muscle damage. CK is often elevated in the presence of muscle damage. The provider may also order a muscle biopsy and an electromyography (EMG) exam. Additional testing may be ordered to see if the potential syndrome is affecting other parts of the body. There are also specific genetic tests that are usually selected based on the presenting symptoms and can be ordered to determine if there is an identifiable genetic cause responsible for the syndrome. This can help with a definitive diagnosis and with understanding the likelihood of disease progression (1).

 

What Treatments
Are Available?

While there are currently no approved treatments or cures for LGMD, there are medical management guidelines, therapies, and recommendations that can improve the quality of life of those living with LGMD. Additionally, many clinical trials and studies are investigating different treatment approaches with varying success that patients may be interested in pursuing. There are also hundreds of different organizations that are working to provide support and services for those with LGMD that can help patients and families get the care they need (1, 2, 3, 14).

 
 

How Can Genetic Counseling Help?

A wheelchair user is sitting at a desk facing away from the camera looking at her open laptop

Genetic counseling can help people suspected of having LGMD and people who are already diagnosed with LGMD. Patients and their families can meet with a genetic counselor to review their family history, and personal medical history, and to learn their risk of having or passing on particular forms of LGMD. For family members of those with LGMD, genetic counseling can help them to understand their risk for the condition or their risk for passing on the gene to their children. After initial genetic counseling, genetic counselors can facilitate specific types of genetic testing that can identify the exact genetic cause of the disorder. Knowing the type of LGMD can also help guide patients and their families to specific organizations and resources working toward bettering the lives of those with their form of LGMD. This can even help patients enter specific clinical trials and better understand their prognosis and progression. Genetic testing can also be performed for family members who want to identify if they are carriers of the condition. Many genetic testing programs offer discounted or free genetic testing to those who consent to sharing their anonymized genetic data for pharmaceutical research aimed at finding treatments and cures for the condition.

 

Citations

  1. Cleveland Clinic. Accessed 4/1/25. Last Reviewed 12/12/23. https://my.clevelandclinic.org/health/diseases/limb-girdle-muscular-dystrophy-lgmd 

  2. National Organization for Rare Disorders (NORD). Accessed 4/1/25, Last updated 10/01/2019. https://rarediseases.org/rare-diseases/limb-girdle-muscular-dystrophies/ 

  3. Muscular Dystrophy Association (MDA). Accessed 4/01/2025. https://www.mda.org/disease/limb-girdle-muscular-dystrophy 

  4. Medline Plus. Accessed 4/1/25, Last updated 9/01/2019. https://medlineplus.gov/genetics/condition/limb-girdle-muscular-dystrophy/#resources 

  5. Cure CMD. Dystroglycanopathy. Accessed 4/01/25. https://www.curecmd.org/dystroglycanopathy 

  6. Munot P, McCrea N, Torelli S, et al. TRAPPC11-related muscular dystrophy with hypoglycosylation of alpha-dystroglycan in skeletal muscle and brain. Neuropathol Appl Neurobiol. 2022; 48(2):e12771. https://doi.org/10.1111/nan.12771 

  7. OMIM #615356. Hilary J. Vernon, Cassandra L. Kniffin. Accessed 4/01/25. Updated 07/02/2024. https://www.omim.org/entry/615356?search=lgmdr18&highlight=lgmdr18 

  8. OMIM #617232. Hilary J. Vernon, Cassandra L. Kniffin. Accessed 4/01/25. Updated 10/04/22. https://www.omim.org/entry/617232?search=lgmd2z&highlight=lgmd2z 

  9. LimbGirdle.com. Accessed 4/01/2025. https://www.limbgirdle.com/lgmd-subtypes

  10. Angelini C. LGMD. Identification, description and classification. Acta Myol 2020;39:207-17. https://doi.org/10.36185/2532-1900-024 

  11. OMIM #603511. Sonja A. Rasmussen, Victor A. McKusick. Accessed 4/02/25. Updated 8/09/22. https://omim.org/entry/603511?search=603511&highlight=603511 

  12. Bisceglia, L., Zoccolella, S., Torraco, A. et al. A new locus on 3p23–p25 for an autosomal-dominant limb-girdle muscular dystrophy, LGMD1H. Eur J Hum Genet 18, 636–641 (2010). https://doi.org/10.1038/ejhg.2009.235

  13. Straub V, Murphy A, Udd B; LGMD workshop study group. 229th ENMC international workshop: Limb girdle muscular dystrophies - Nomenclature and reformed classification Naarden, the Netherlands, 17-19 March 2017. Neuromuscul Disord. 2018 Aug;28(8):702-710. doi: 10.1016/j.nmd.2018.05.007. Epub 2018 May 24. PMID: 30055862. https://www.nmd-journal.com/action/showPdf?pii=S0960-8966%2818%2930214-1

  14. LimbGirdle.com. Accessed 4/01/25. https://www.limbgirdle.com/disease-management