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Muscular dystrophy, limb-girdle, autosomal recessive 26(LGMDR26)

MedGen UID:
1718449
Concept ID:
C5394268
Disease or Syndrome
Synonyms: LGMDR26; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 26
 
Gene (location): POPDC3 (6q21)
 
Monarch Initiative: MONDO:0030014
OMIM®: 618848

Definition

Autosomal recessive limb-girdle muscular dystrophy-26 (LGMDR26) is a muscle disorder characterized by adult-onset weakness that primarily affects the proximal muscles of the lower limbs. The disorder is slowly progressive, with later involvement of the upper limbs and fatty replacement of muscle tissue apparent on MRI. Some patients may have calf hypertrophy. Serum creatine kinase is significantly elevated, and skeletal muscle biopsy shows typical dystrophic features with normal ultrastructural findings. There is no cardiac or respiratory involvement (summary by Vissing et al., 2019). For a discussion of genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy, see LGMDR1 (253600). [from OMIM]

Clinical features

From HPO
Falls
MedGen UID:
39084
Concept ID:
C0085639
Finding
A sudden movement downward, usually resulting in injury.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Difficulty running
MedGen UID:
108251
Concept ID:
C0560346
Finding
Reduced ability to run.
Calf muscle hypertrophy
MedGen UID:
335868
Concept ID:
C1843057
Finding
Muscle hypertrophy affecting the calf muscles.
Increased variability in muscle fiber diameter
MedGen UID:
336019
Concept ID:
C1843700
Finding
An abnormally high degree of muscle fiber size variation. This phenotypic feature can be observed upon muscle biopsy.
Muscle fiber necrosis
MedGen UID:
376893
Concept ID:
C1850848
Pathologic Function
Abnormal cell death involving muscle fibers usually associated with break in, or absence of, muscle surface fiber membrane and resulting in irreversible damage to muscle fibers.
Proximal muscle weakness in lower limbs
MedGen UID:
356423
Concept ID:
C1866010
Finding
A lack of strength of the proximal muscles of the legs.
Fatty replacement of skeletal muscle
MedGen UID:
866735
Concept ID:
C4021082
Finding
Muscle fibers degeneration resulting in fatty replacement of skeletal muscle fibers
Highly elevated creatine kinase
MedGen UID:
868173
Concept ID:
C4022565
Finding
An increased CPK level between 4X and 50X above the upper normal level.

Professional guidelines

PubMed

Chu ML, Moran E
Neurotherapeutics 2018 Oct;15(4):849-862. doi: 10.1007/s13311-018-0648-x. PMID: 30019308Free PMC Article

Recent clinical studies

Etiology

Lorenzoni PJ, Kay CSK, Ducci RD, Fustes OJH, Rodrigues PRDVP, Hrysay NMC, Arndt RC, Werneck LC, Scola RH
Arq Neuropsiquiatr 2023 Oct;81(10):922-933. Epub 2023 Oct 18 doi: 10.1055/s-0043-1772833. PMID: 37852290Free PMC Article
Ten Dam L, Frankhuizen WS, Linssen WHJP, Straathof CS, Niks EH, Faber K, Fock A, Kuks JB, Brusse E, de Coo R, Voermans N, Verrips A, Hoogendijk JE, van der Pol L, Westra D, de Visser M, van der Kooi AJ, Ginjaar I
Clin Genet 2019 Aug;96(2):126-133. Epub 2019 May 6 doi: 10.1111/cge.13544. PMID: 30919934
Chu ML, Moran E
Neurotherapeutics 2018 Oct;15(4):849-862. doi: 10.1007/s13311-018-0648-x. PMID: 30019308Free PMC Article
Liewluck T, Milone M
Muscle Nerve 2018 Aug;58(2):167-177. Epub 2018 Feb 7 doi: 10.1002/mus.26077. PMID: 29350766
Straub V, Bertoli M
Neuromuscul Disord 2016 Feb;26(2):111-25. Epub 2015 Dec 18 doi: 10.1016/j.nmd.2015.11.012. PMID: 26810373

Diagnosis

Wang N, Han X, Hao S, Han J, Zhou X, Sun S, Tang J, Lu Y, Wu H, Ma S, Song X, Ji G
BMC Neurol 2022 Nov 1;22(1):398. doi: 10.1186/s12883-022-02905-w. PMID: 36319958Free PMC Article
Quick S, Winkler M, Speiser U, Ibrahim K, Schäfer J, Linke A, Zhang K, Christoph M, Heidrich FM
Orphanet J Rare Dis 2021 Apr 30;16(1):194. doi: 10.1186/s13023-021-01826-0. PMID: 33931068Free PMC Article
Ten Dam L, Frankhuizen WS, Linssen WHJP, Straathof CS, Niks EH, Faber K, Fock A, Kuks JB, Brusse E, de Coo R, Voermans N, Verrips A, Hoogendijk JE, van der Pol L, Westra D, de Visser M, van der Kooi AJ, Ginjaar I
Clin Genet 2019 Aug;96(2):126-133. Epub 2019 May 6 doi: 10.1111/cge.13544. PMID: 30919934
Inashkina I, Jankevics E, Stavusis J, Vasiljeva I, Viksne K, Micule I, Strautmanis J, Naudina MS, Cimbalistiene L, Kucinskas V, Krumina A, Utkus A, Burnyte B, Matuleviciene A, Lace B
BMC Musculoskelet Disord 2016 May 4;17:200. doi: 10.1186/s12891-016-1058-z. PMID: 27142102Free PMC Article
Straub V, Bertoli M
Neuromuscul Disord 2016 Feb;26(2):111-25. Epub 2015 Dec 18 doi: 10.1016/j.nmd.2015.11.012. PMID: 26810373

Therapy

Chu ML, Moran E
Neurotherapeutics 2018 Oct;15(4):849-862. doi: 10.1007/s13311-018-0648-x. PMID: 30019308Free PMC Article
Straub V, Bertoli M
Neuromuscul Disord 2016 Feb;26(2):111-25. Epub 2015 Dec 18 doi: 10.1016/j.nmd.2015.11.012. PMID: 26810373
Walter MC, Reilich P, Thiele S, Schessl J, Schreiber H, Reiners K, Kress W, Müller-Reible C, Vorgerd M, Urban P, Schrank B, Deschauer M, Schlotter-Weigel B, Kohnen R, Lochmüller H
Orphanet J Rare Dis 2013 Feb 14;8:26. doi: 10.1186/1750-1172-8-26. PMID: 23406536Free PMC Article

Prognosis

Quick S, Winkler M, Speiser U, Ibrahim K, Schäfer J, Linke A, Zhang K, Christoph M, Heidrich FM
Orphanet J Rare Dis 2021 Apr 30;16(1):194. doi: 10.1186/s13023-021-01826-0. PMID: 33931068Free PMC Article
Fatehi F, Nafissi S, Urtizberea JA, Blanck-Labelle V, Lévy N, Krahn M, Dbouk MB, Attarian S
J Neurol Sci 2015 Dec 15;359(1-2):256-9. Epub 2015 Nov 11 doi: 10.1016/j.jns.2015.11.009. PMID: 26671124
Walter MC, Reilich P, Thiele S, Schessl J, Schreiber H, Reiners K, Kress W, Müller-Reible C, Vorgerd M, Urban P, Schrank B, Deschauer M, Schlotter-Weigel B, Kohnen R, Lochmüller H
Orphanet J Rare Dis 2013 Feb 14;8:26. doi: 10.1186/1750-1172-8-26. PMID: 23406536Free PMC Article
van der Kooi AJ, de Voogt WG, Barth PG, Busch HF, Jennekens FG, Jongen PJ, de Visser M
Heart 1998 Jan;79(1):73-7. doi: 10.1136/hrt.79.1.73. PMID: 9505924Free PMC Article

Clinical prediction guides

Quick S, Winkler M, Speiser U, Ibrahim K, Schäfer J, Linke A, Zhang K, Christoph M, Heidrich FM
Orphanet J Rare Dis 2021 Apr 30;16(1):194. doi: 10.1186/s13023-021-01826-0. PMID: 33931068Free PMC Article
Mojbafan M, Nilipour Y, Tonekaboni SH, Bagheri SD, Bagherian H, Sharifi Z, Zeinali Z, Tavakkoly-Bazzaz J, Zeinali S
J Neurogenet 2016 Mar;30(1):1-4. doi: 10.3109/01677063.2016.1141208. PMID: 27276190
Walter MC, Reilich P, Thiele S, Schessl J, Schreiber H, Reiners K, Kress W, Müller-Reible C, Vorgerd M, Urban P, Schrank B, Deschauer M, Schlotter-Weigel B, Kohnen R, Lochmüller H
Orphanet J Rare Dis 2013 Feb 14;8:26. doi: 10.1186/1750-1172-8-26. PMID: 23406536Free PMC Article
Hanisch F, Müller CR, Grimm D, Xue L, Traufeller K, Merkenschlager A, Zierz S, Deschauer M
Clin Neuropathol 2007 Jul-Aug;26(4):157-63. doi: 10.5414/npp26157. PMID: 17702496
Voit T, Stuettgen P, Cremer M, Goebel HH
Neuropediatrics 1991 Aug;22(3):152-62. doi: 10.1055/s-2008-1071434. PMID: 1944822

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