Limb–girdle muscular dystrophy

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Limb–girdle muscular dystrophy
Other names: Myopathic limb-girdle syndrome,[1] Erb's muscular dystrophy[2]
Schematic of the etiology of subgroups of LGMDs.[3]
TypesLGMD1 and LGMD2[4]
Diagnostic methodImmunohistochemical dystrophin tests[5]
TreatmentOccupational, speech and physical therapy[6]

Limb–girdle muscular dystrophy or (LGMD) is a genetically and clinically heterogeneous group of rare muscular dystrophies.[7]

It is characterised by progressive muscle wasting which affects predominantly hip and shoulder muscles. LGMD has an autosomal pattern of inheritance and currently has no known cure or treatment.[8][9]

In terms of research there is a gene therapy approach. Atamyo Therapeutics received approval from regulators in the European countries of France and Italy to start clinical trial testing ATA-200.[10]


The "LGMD1" family is autosomal dominant, and the "LGMD2" family is autosomal recessive.[9]

Limb–girdle muscular dystrophy is explained in terms of gene, locus, OMIM and type as follows:

Family Inheritance Type OMIM Gene Locus Notes
LGMD1 autosomal dominant
LGMD1A 159000 TTID
LGMD1B 159001 LMNA
LGMD1C 607801 CAV3
LGMD1D 603511 DNAJB6
LGMD1E 601419 DES
LGMD1F 608423 TNPO3 7q32.1–q32.2
LGMD1G 609115 HNRPDL 4q21
LGMD1H 613530 3p25.1–p23
LGMD2 autosomal recessive
LGMD2A 253600 CAPN3 Often referred to as "calpainopathy."[11]
LGMD2B 253601 DYSF LGMD with a mutation in this gene, along with Miyoshi Myopathy type 1 (MMD1 - 254130) are sometimes called dysferlinopathies.[12]
LGMD2C 253700 SGCG
LGMD2D 608099 SGCA
LGMD2E 604286 SGCB
LGMD2F 601287 SGCD
LGMD2G 601954 TCAP
LGMD2H 254110 TRIM32
LGMD2I 607155 FKRP
LGMD2J 608807 TTN
LGMD2K 609308 POMT1
LGMD2L 611307 ANO5
LGMD2M 611588 FKTN
LGMD2N 607439 POMT2
LGMD2Q 613723 PLEC1

Signs and symptoms

a) Winging of scapula presented passively b) Calf hypertrophy

The symptoms of an individual with limb–girdle muscular dystrophy (LGMD) generally are great difficulty walking, going both up and down stairs, and rising from a chair. The inability to bend over or squat down is also present. Because of these difficulties, falling can occur frequently. Lifting certain objects, as well as difficulty extending the arms out or above the head, varies from difficult to impossible depending on the severity. Eventually, the abilities to walk and run deteriorate.[1][5]

Further presentations an individual with LGMD might have are:

The disease inevitably gets worse over time, although progression is more rapid in some patients than others. Eventually the disease can affect other muscles such as the ones located in the face. The disease commonly leads to dependence on a wheelchair within years of symptom onset, but there is high inter-patient variability, with some patients maintaining mobility.[9][1]

The muscle weakness is generally symmetric, proximal, and slowly progressive. In most cases, pain is not present with LGMD, and mental function is not affected. LGMD can begin in childhood, adolescence, young adulthood or even later, the age of onset is usually between 10 and 30. Both genders are affected equally, when limb-girdle muscular dystrophy begins in childhood the progression appears to be faster and the disease more disabling. When the disorder begins in adolescence or adulthood the disease is generally not as severe and progresses more slowly. There is no sensory neuropathy or autonomic or visceral dysfunction at presentation.[medical citation needed]


In terms of the genetics LGMD is an inherited disorder, though it may be inherited as a dominant or recessive genetic defect. The result of the defect is that the muscles cannot properly form certain proteins needed for normal muscle function. Several different proteins can be affected, and the specific protein that is absent or defective identifies the specific type of muscular dystrophy. Among the proteins affected in LGMD are α, β, γ and δ sarcoglycans. The sarcoglycanopathies could be possibly amenable to gene therapy.[4]


The diagnosis of limb–girdle muscular dystrophy can be done via muscle biopsy, which will show the presence of muscular dystrophy, and genetic testing is used to determine which type of muscular dystrophy a patient has. Immunohistochemical dystrophin tests can indicate a decrease in dystrophin detected in sarcoglycanopathies. In terms of sarcoglycan deficiency there can be variance (if α-sarcoglycan and γ-sarcoglycan are not present then there's a mutation in LGMD2D).[5]

The 2014 Evidence-based guideline summary: Diagnosis and treatment of limb–girdle and distal dystrophies indicates that individuals suspected of having the inherited disorder should have genetic testing. Other tests/analysis are:[5][6]

  • High CK levels(x10-150 times normal)
  • MRI can indicate different types of LGMD.
  • EMG can confirm the myopathic characteristic of the disease.
  • Electrocardiography (cardiac arrhythmias in LGMD1B can occur)


Cardiac muscle

There are few studies corroborating the effectiveness of exercise for limb–girdle muscular dystrophy. However studies have shown that exercise can, in fact, damage muscles permanently due to intense muscle contraction.[14] Physical therapy may be required to maintain as much muscle strength and joint flexibility as possible. Calipers may be used to maintain mobility and quality of life. Careful attention to lung and heart health is required, corticosteroids in LGMD 2C-F individuals, shows some improvement.[13] Additionally individuals can follow management that follows:[6]

In terms of the prognosis of limb–girdle muscular dystrophy in its mildest form, affected individuals have near-normal muscle strength and function. LGMD isn't typically a fatal disease, though it may eventually weaken the heart and respiratory muscles, leading to illness or death due to secondary disorders. The frequency of limb–girdle muscular dystrophy ranges from 1 in 14,500 (in some instances 1 in 123,000).[7][9]


alpha sarcoglycan Left side-normal muscle /right side LGMD2

There is a variety of research under way targeted at various forms of limb–girdle muscular dystrophy. Among the methods thought to hold promise for treatment include gene transfer therapy,[15] which works by inserting in cells of defective genes with a healthy gene.[16]

According to a review by Bengtsson et al. some success with AAV-mediated gene therapies (for different disorders) have increased interest in researchers, with CRISPR/Cas9 and exon-skipping helping these therapeutic goals along. Limb–girdle muscular dystrophies have many different types which are due to different gene mutations. LGMD2D is caused by a mutation in the α-sarcoglycan gene. Future treatment could be had by gene therapy through recombinant adeno-associated vectors.[17]

Conversely, according to a review by Straub, et al. there are several research issues that need to be targeted, the rareness of the disease, our poor understanding of the mechanism of LGMD2, and absence of patient cohorts, consequently biomarkers for individuals with LGMD2 are lacking. The review goes on to state that animal models for LGMD2 have been used to analyse therapeutic medications. Also adding that while prednisone has been used and has had positive effects on affected LGMD2 individuals there is still no evidence of its effectiveness in trials that are placebo-controlled.[18]

See also


  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 MedlinePlus Encyclopedia: Limb-girdle muscular dystrophies
  2. Newfoundland, FRCP William Pryse-Phillips MD, FRCP(C) Faculty of Medicine Health Sciences Centre Memorial University of Newfoundland St John's (2009-05-06). Companion to Clinical Neurology. Oxford University Press, USA. p. 579. ISBN 9780199710041. Archived from the original on 2020-05-14. Retrieved 2021-08-08.
  3. Rawls, Alan; Diviak, Bridget K.; Smith, Cameron I.; Severson, Grant W.; Acosta, Sofia A.; Wilson-Rawls, Jeanne (October 2023). "Pharmacotherapeutic Approaches to Treatment of Muscular Dystrophies". Biomolecules. 13 (10): 1536. doi:10.3390/biom13101536. ISSN 2218-273X. Archived from the original on 2024-05-19. Retrieved 2024-05-19.
  4. 4.0 4.1 Reference, Genetics Home. "limb-girdle muscular dystrophy". Genetics Home Reference. Archived from the original on 2020-09-28. Retrieved 2016-04-22.
  5. 5.0 5.1 5.2 5.3 "Limb-Girdle Muscular Dystrophy: Practice Essentials, Background, Pathophysiology". August 2018. Archived from the original on 2021-04-11. Retrieved 2021-08-08. {{cite journal}}: Cite journal requires |journal= (help)
  6. 6.0 6.1 6.2 Narayanaswami, Pushpa; Weiss, Michael; Selcen, Duygu; David, William; Raynor, Elizabeth; Carter, Gregory; Wicklund, Matthew; Barohn, Richard J.; Ensrud, Erik (2014-10-14). "Evidence-based guideline summary: Diagnosis and treatment of limb-girdle and distal dystrophies". Neurology. 83 (16): 1453–1463. doi:10.1212/WNL.0000000000000892. ISSN 0028-3878. PMC 4206155. PMID 25313375.
  7. 7.0 7.1 "Limb-girdle muscular dystrophy". Archived from the original on 2020-09-28. Retrieved 2021-08-08.
  8. "Limb-Girdle Muscular Dystrophy Treatment & Management: Medical Care, Surgical Care, Consultations". August 2018. Archived from the original on 2021-01-28. Retrieved 2021-08-08. {{cite journal}}: Cite journal requires |journal= (help)
  9. 9.0 9.1 9.2 9.3 Pegoraro, Elena; Hoffman, Eric P. (1993-01-01). Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora JH; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C. (eds.). Limb-Girdle Muscular Dystrophy Overview. Seattle (WA): University of Washington, Seattle. PMID 20301582. Archived from the original on 2017-01-18. Retrieved 2021-08-08.update 2012
  10. Berthomier, Anne (8 April 2024). "Atamyo Therapeutics obtains authorisation to launch a gene therapy clinical trial in limb-girdle muscular dystrophy linked to SGCG". Institut de Myologie. Archived from the original on 22 May 2024. Retrieved 19 May 2024.
  11. Lasa-Elgarresta, J; Mosqueira-Martín, L; Naldaiz-Gastesi, N; Sáenz, A; López de Munain, A; Vallejo-Illarramendi, A (13 September 2019). "Calcium Mechanisms in Limb-Girdle Muscular Dystrophy with CAPN3 Mutations". International Journal of Molecular Sciences. 20 (18): 4548. doi:10.3390/ijms20184548. PMC 6770289. PMID 31540302.
  12. Aoki, Masashi (March 5, 2015). "Dysferlinopathy". GeneReviews. Archived from the original on February 18, 2019. Retrieved August 8, 2021.
  13. 13.0 13.1 13.2 13.3 "Limb-girdle Muscular Dystrophy | Doctor". Archived from the original on 2021-03-06. Retrieved 2021-08-08.
  14. Siciliano G, Simoncini C, Giannotti S, Zampa V, Angelini C, Ricci G (2015). "Muscle exercise in limb girdle muscular dystrophies: pitfall and advantages". Acta Myologica. 34 (1): 3–8. PMC 4478773. PMID 26155063.
  15. Liaison, Melanie Martinez, Office of Communications and Public. "Limb-Girdle Muscular Dystrophy". Archived from the original on 2016-04-06. Retrieved 2016-04-22.
  16. Reference, Genetics Home. "How does gene therapy work?". Genetics Home Reference. Archived from the original on 2019-12-05. Retrieved 2016-04-23.
  17. Bengtsson, Niclas E.; Seto, Jane T.; Hall, John K.; Chamberlain, Jeffrey S.; Odom, Guy L. (2016-04-15). "Progress and prospects of gene therapy clinical trials for the muscular dystrophies". Human Molecular Genetics. 25 (R1): R9–R17. doi:10.1093/hmg/ddv420. ISSN 0964-6906. PMC 4802376. PMID 26450518.
  18. Straub, Volker; Bertoli, Marta (2016-02-01). "Where do we stand in trial readiness for autosomal recessive limb girdle muscular dystrophies?". Neuromuscular Disorders. 26 (2): 111–125. doi:10.1016/j.nmd.2015.11.012. PMID 26810373. S2CID 23787096. – via ScienceDirect (Subscription may be required or content may be available in libraries.)

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