The limb-girdle muscular dystrophies are a group of diseases that cause muscle weakness (myopathy) and wasting (atrophy). The muscles that are most affected are those closest to the center of the body (proximal muscles), specifically the muscles of the shoulders, upper arms, hips, and thighs. Signs and symptoms may appear as early as childhood and typically worsen over time.

The severity, age of onset, and specific features of limb-girdle muscle dystrophy vary among affected individuals, even among members of the same family. 

In the early stages of limb-girdle muscular dystrophy, affected individuals may have an unusual walking gait, such as waddling or walking on the balls of their feet. Walking this way for an extended period of time can cause overgrowth (hypertrophy) of the calf muscles. Affected individuals may also have difficulty running. They may need to use their arms to push themselves up from a squatting position because of their weak thigh muscles. Over time, as myopathy and atrophy worsen, people with limb-girdle muscular dystrophy may require wheelchair assistance.

Muscle atrophy may cause changes in posture or in the appearance of the shoulders, back, and arms. In particular, weak shoulder muscles tend to make the shoulder blades (scapulae) "stick out" from the back, a sign known as scapular winging. Weak back muscles may also cause an affected individual to have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Some affected individuals develop joint stiffness (contractures) that can restrict movement in their hips, knees, ankles, or elbows.

A weakening of the heart muscle (cardiomyopathy) occurs in some people with limb-girdle muscular dystrophy. If the weakness affects the muscles needed for breathing, affected individuals may have mild to severe breathing problems. In some cases, affected individuals need a machine to help them breathe (mechanical ventilation).

Intelligence is generally not affected in people with limb-girdle muscular dystrophy. However, developmental delays and intellectual disabilities have been reported in some affected individuals who have signs and symptoms that are more severe or that appear earlier in life.

It is estimated that between 1 in 14,500 and 1 in 123,000 individuals have limb-girdle muscular dystrophy. It is difficult to determine the exact number of people with this condition because the features vary and may overlap with those of other muscle disorders.

Variants (also called mutations) in over 32 genes cause limb-girdle muscular dystrophy. These genes provide instructions for making proteins that are involved in muscle maintenance and repair.

Some of the proteins produced from these genes help maintain the organization and structure of muscle tissue, which allows the muscles to contract. Other proteins participate in cell signaling, cell membrane repair, or the removal of toxic waste from muscle cells.

Researchers have described several types of limb-girdle muscular dystrophy. The names for the different types include the abbreviation LGMD followed by the pattern of inheritance, a number, and the cause. Within this classification, the letter "D" is used for the forms of the disorder that have an inheritance pattern called autosomal dominant. The letter "R" is used for the forms of the disorder that have an inheritance pattern called autosomal recessive. The name also includes a number that indicates the order in which the disease was discovered, and it may include the name of the specific protein that is affected. As an example, “LGMD R1 calpain-3-related” refers to the first autosomal recessive limb-girdle muscular dystrophy to be discovered, which is caused by changes in the calpain-3 enzyme. 

Variants in the CAPN3 gene are the most common cause of limb-girdle muscular dystrophy. This gene provides instructions for making an enzyme called calpain-3. The calpain-3 enzyme cuts (cleaves) damaged proteins into shorter segments so that they can be easily removed from the muscle cell. CAPN3 gene variants lead to the production of an enzyme that does not function properly. As a result, damaged proteins are not removed from muscle cells and muscle function is impaired. CAPN3 gene variants cause the LGMD R1 calpain-3-related type and the LGMD D4 calpain-3-related type of limb-girdle muscular dystrophy.

Variants in the DYSF gene are another common cause of limb-girdle muscular dystrophy. The DYSF gene provides instructions for making a protein called dysferlin, which is found in the thin membrane that surrounds muscle fibers. Dysferlin is thought to help repair this membrane when it becomes damaged due to muscle strain. DYSF gene variants cause cells to produce an altered version of the protein that cannot help with muscle repair. DYSF gene variants cause the LGMD R2 dysferlin-related type of limb-girdle muscular dystrophy.

Variants in the other genes that are associated with limb-girdle muscular dystrophy each account for a small percentage of cases.

In some people with limb-girdle muscular dystrophy, the genetic cause of the disorder is unknown.

Genetic Testing Information

• Genetic Testing Registry: Limb-girdle muscular dystrophy

Genetic and Rare Diseases Information Center

• Limb-girdle muscular dystrophy

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 7; LGMDR7
• MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 6; LGMDR6
• MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1; LGMDR1
• MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 2; LGMDR2
• MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 5; LGMDR5
• MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 8; LGMDR8
• MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL DOMINANT 1; LGMDD1
• MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 4; LGMDR4
• MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 10; LGMDR10
• MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 5; MDDGC5
• MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 3; LGMDR3
• MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL DOMINANT 2; LGMDD2
• MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 12; LGMDR12
• MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL DOMINANT 3; LGMDD3
• MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 1; MDDGC1
• MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 4; MDDGC4
• MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 14; MDDGC14
• MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 18; LGMDR18
• MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 3; MDDGC3
• MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 2; MDDGC2
• MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 1H; LGMD1H
• MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 17; LGMDR17
• MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 12; MDDGC12
• MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL DOMINANT 4; LGMDD4
• MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 8; MDDGC8
• MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 7; MDDGC7
• MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 21; LGMDR21
• MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 9; MDDGC9

Scientific Articles on PubMed

• PubMed

• Angelini C, Giaretta L, Marozzo R. An update on diagnostic options and considerations in limb-girdle dystrophies. Expert Rev Neurother. 2018 Sep;18(9):693-703. doi: 10.1080/14737175.2018.1508997. Epub 2018 Aug 21. Citation on PubMed
• Angelini C. Calpainopathy. 2005 May 10 [updated 2025 May 1]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1313/ Citation on PubMed
• Aoki M, Takahashi T. Dysferlinopathy. 2004 Feb 5 [updated 2021 May 27]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1303/ Citation on PubMed
• Bouchard C, Tremblay JP. Limb-Girdle Muscular Dystrophies Classification and Therapies. J Clin Med. 2023 Jul 19;12(14):4769. doi: 10.3390/jcm12144769. Citation on PubMed
• Chu ML, Moran E. The Limb-Girdle Muscular Dystrophies: Is Treatment on the Horizon? Neurotherapeutics. 2018 Oct;15(4):849-862. doi: 10.1007/s13311-018-0648-x. Citation on PubMed or Free article on PubMed Central
• Khadilkar SV, Patel BA, Lalkaka JA. Making sense of the clinical spectrum of limb girdle muscular dystrophies. Pract Neurol. 2018 Jun;18(3):201-210. doi: 10.1136/practneurol-2017-001799. Epub 2018 Feb 22. Citation on PubMed
• Liewluck T, Milone M. Untangling the complexity of limb-girdle muscular dystrophies. Muscle Nerve. 2018 Aug;58(2):167-177. doi: 10.1002/mus.26077. Epub 2018 Feb 7. Citation on PubMed
• Liu W, Pajusalu S, Lake NJ, Zhou G, Ioannidis N, Mittal P, Johnson NE, Weihl CC, Williams BA, Albrecht DE, Rufibach LE, Lek M. Estimating prevalence for limb-girdle muscular dystrophy based on public sequencing databases. Genet Med. 2019 Nov;21(11):2512-2520. doi: 10.1038/s41436-019-0544-8. Epub 2019 May 20. Citation on PubMed
• Mah JK, Korngut L, Fiest KM, Dykeman J, Day LJ, Pringsheim T, Jette N. A Systematic Review and Meta-analysis on the Epidemiology of the Muscular Dystrophies. Can J Neurol Sci. 2016 Jan;43(1):163-77. doi: 10.1017/cjn.2015.311. Citation on PubMed
• Mitsuhashi S, Kang PB. Update on the genetics of limb girdle muscular dystrophy. Semin Pediatr Neurol. 2012 Dec;19(4):211-8. doi: 10.1016/j.spen.2012.09.008. Citation on PubMed
• Mohan S, McNulty S, Thaxton C, Elnagheeb M, Owens E, Flowers M, Nunnery T, Self A, Palus B, Gorokhova S, Kennedy A, Niu Z, Johari M, Maiga AB, Macalalad K, Clause AR, Beckmann JS, Bronicki L, Cooper ST, Ganesh VS, Kang PB, Kesari A, Lek M, Levy J, Rufibach L, Savarese M, Spencer MJ, Straub V, Tasca G, Weihl CC. Expert panel curation of 31 genes in relation to limb girdle muscular dystrophy. Ann Clin Transl Neurol. 2024 Sep;11(9):2268-2276. doi: 10.1002/acn3.52127. Epub 2024 Aug 30. Citation on PubMed
• Nallamilli BRR, Chakravorty S, Kesari A, Tanner A, Ankala A, Schneider T, da Silva C, Beadling R, Alexander JJ, Askree SH, Whitt Z, Bean L, Collins C, Khadilkar S, Gaitonde P, Dastur R, Wicklund M, Mozaffar T, Harms M, Rufibach L, Mittal P, Hegde M. Genetic landscape and novel disease mechanisms from a large LGMD cohort of 4656 patients. Ann Clin Transl Neurol. 2018 Dec 1;5(12):1574-1587. doi: 10.1002/acn3.649. eCollection 2018 Dec. Citation on PubMed
• Poudel BH, Fletcher S, Wilton SD, Aung-Htut M. Limb Girdle Muscular Dystrophy Type 2B (LGMD2B): Diagnosis and Therapeutic Possibilities. Int J Mol Sci. 2024 May 21;25(11):5572. doi: 10.3390/ijms25115572. Citation on PubMed
• 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. No abstract available. Citation on PubMed
• Thompson R, Straub V. Limb-girdle muscular dystrophies - international collaborations for translational research. Nat Rev Neurol. 2016 May;12(5):294-309. doi: 10.1038/nrneurol.2016.35. Epub 2016 Apr 1. Citation on PubMed
• Wicklund MP, Kissel JT. The limb-girdle muscular dystrophies. Neurol Clin. 2014 Aug;32(3):729-49, ix. doi: 10.1016/j.ncl.2014.04.005. Citation on PubMed