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Limb-girdle muscular dystrophy(LGMD)

MedGen UID:
151940
Concept ID:
C0686353
Disease or Syndrome
Synonyms: LGMD; Muscular Dystrophies, Limb-Girdle
SNOMED CT: Muscular dystrophy with predominantly proximal limb girdle distribution (240046001); Limb-girdle muscular dystrophy (240046001)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Genes (locations): DYSF (2p13.2); SGCB (4q12); SGCD (5q33.2-33.3)
Related genes: ANO5, MYLK2, FKRP, TRAPPC11, POMGNT1, TNPO3, TRIM32, DNAJB6, HNRNPDL, MYOT, TCAP, TTN, SGCG, SGCA, PLEC, MYH7, MYH6, LMNA, FKTN, DES, DAG1, CAV3, CAPN3
 
HPO: HP:0006785
Monarch Initiative: MONDO:0016971
Orphanet: ORPHA263

Definition

Limb-girdle muscular dystrophy is a term for a group of diseases that cause weakness and wasting of the muscles in the arms and legs. The muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area, and thighs.

The severity, age of onset, and features of limb-girdle muscle dystrophy vary among the many subtypes of this condition and may be inconsistent even within the same family. Signs and symptoms may first appear at any age and generally worsen with time, although in some cases they remain mild.

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, and may also have difficulty running. They may need to use their arms to press themselves up from a squatting position because of their weak thigh muscles. As the condition progresses, people with limb-girdle muscular dystrophy may eventually require wheelchair assistance.

Muscle wasting may cause changes in posture or in the appearance of the shoulder, back, and arm. In particular, weak shoulder muscles tend to make the shoulder blades (scapulae) "stick out" from the back, a sign known as scapular winging. Affected individuals may also have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Some develop joint stiffness (contractures) that can restrict movement in their hips, knees, ankles, or elbows. Overgrowth (hypertrophy) of the calf muscles occurs in some people with limb-girdle muscular dystrophy.

Weakening of the heart muscle (cardiomyopathy) occurs in some forms of limb-girdle muscular dystrophy. Some affected individuals experience mild to severe breathing problems related to the weakness of muscles needed for breathing. In some cases, the breathing problems are severe enough that affected individuals need to use a machine to help them breathe (mechanical ventilation).

Intelligence is generally unaffected in limb-girdle muscular dystrophy; however, developmental delay and intellectual disability have been reported in rare forms of the disorder. [from MedlinePlus Genetics]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Limb-girdle muscular dystrophy in Orphanet.

Conditions with this feature

Emery-Dreifuss muscular dystrophy 2, autosomal dominant
MedGen UID:
98048
Concept ID:
C0410190
Disease or Syndrome
Emery-Dreifuss muscular dystrophy (EDMD) is characterized by the clinical triad of: joint contractures that begin in early childhood; slowly progressive muscle weakness and wasting initially in a humero-peroneal distribution that later extends to the scapular and pelvic girdle muscles; and cardiac involvement that may manifest as palpitations, presyncope and syncope, poor exercise tolerance, and congestive heart failure along with variable cardiac rhythm disturbances. Age of onset, severity, and progression of muscle and cardiac involvement demonstrate both inter- and intrafamilial variability. Clinical variability ranges from early onset with severe presentation in childhood to late onset with slow progression in adulthood. In general, joint contractures appear during the first two decades, followed by muscle weakness and wasting. Cardiac involvement usually occurs after the second decade and respiratory function may be impaired in some individuals.
Autosomal dominant limb-girdle muscular dystrophy type 1G
MedGen UID:
322993
Concept ID:
C1836765
Disease or Syndrome
Autosomal dominant limb-girdle muscular dystrophy-3 (LGMDD3) is characterized by slowly progressive proximal muscle weakness affecting the upper and lower limbs. Onset is usually in adulthood, but can occur during the teenage years. Affected individuals may also develop cataracts before age 50 (summary by Vieira et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of autosomal dominant limb-girdle muscular dystrophy, see LGMDD1 (603511).
Muscular dystrophy, Hemizygous lethal type
MedGen UID:
326552
Concept ID:
C1839671
Disease or Syndrome
DPM3-congenital disorder of glycosylation
MedGen UID:
414534
Concept ID:
C2752007
Disease or Syndrome
Limb-girdle muscular dystrophy-dystroglycanopathy type C15 (MDDGC15) is an autosomal recessive disorder characterized by progressive proximal muscle weakness, manifest initially as unsteady gait, but later including more distal muscles, and dilated cardiomyopathy. The age at onset varies widely from the first decade to adulthood; those with earlier onset may have delayed motor development. Laboratory studies show increased serum creatine kinase and muscle biopsy shows dystrophic features with decreased alpha-dystroglycan (DAG1; 128239). Biochemical studies often show evidence of abnormal N-glycosylation of serum proteins, consistent with a congenital disorder of glycosylation (CDG) (summary by Svahn et al., 2019). For a discussion of genetic heterogeneity of muscular dystrophy- dystroglycanopathy type C, see MDDGC1 (609308). For a discussion of the classification of CDGs, see CDG1A (212065).
Autosomal recessive limb-girdle muscular dystrophy type 2D
MedGen UID:
424706
Concept ID:
C2936332
Disease or Syndrome
Autosomal recessive limb-girdle muscular dystrophy-3 (LGMDR3) affects mainly the proximal muscles and results in difficulty walking. Most individuals have onset in childhood; the disorder is progressive. Other features may include scapular winging, calf pseudohypertrophy, and contractures. Cardiomyopathy has rarely been reported (summary by Babameto-Laku et al., 2011). For a discussion of genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy, see LGMDR1 (253600).
Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3
MedGen UID:
815799
Concept ID:
C3809469
Disease or Syndrome
Inclusion body myopathy associated with Paget disease of bone (PDB) and/or frontotemporal dementia (IBMPFD) is characterized by adult-onset proximal and distal muscle weakness (clinically resembling a limb-girdle muscular dystrophy syndrome), early-onset PDB, and premature frontotemporal dementia (FTD). Muscle weakness progresses to involve other limb and respiratory muscles. PDB involves focal areas of increased bone turnover that typically lead to spine and/or hip pain and localized enlargement and deformity of the long bones; pathologic fractures occur on occasion. Early stages of FTD are characterized by dysnomia, dyscalculia, comprehension deficits, and paraphasic errors, with minimal impairment of episodic memory; later stages are characterized by inability to speak, auditory comprehension deficits for even one-step commands, alexia, and agraphia. Mean age at diagnosis for muscle disease and PDB is 42 years; for FTD, 56 years. Dilated cardiomyopathy, amyotrophic lateral sclerosis, and Parkinson disease are now known to be part of the spectrum of findings associated with IBMPFD.
Autosomal recessive limb-girdle muscular dystrophy type 2R1
MedGen UID:
934627
Concept ID:
C4310660
Disease or Syndrome
Autosomal recessive limb-girdle muscular dystrophy-21 (LGMDR21) is characterized by progressive limb-girdle weakness with age of onset ranging from congenital to adult. Muscle imaging shows a specific and selective pattern of fatty muscle degeneration (summary by Servian-Morilla et al., 2020). For a discussion of genetic heterogeneity of autosomal recessive LGMD, see LGMDR1 (253600).
Autosomal recessive limb-girdle muscular dystrophy type R18
MedGen UID:
1385598
Concept ID:
C4517996
Disease or Syndrome
Autosomal recessive limb-girdle muscular dystrophy-18 (LGMD18) is characterized by childhood-onset of proximal muscle weakness resulting in gait abnormalities and scapular winging. Serum creatine kinase is increased. A subset of patients may show a hyperkinetic movement disorder with chorea, ataxia, or dystonia and global developmental delay (summary by Bogershausen et al., 2013). Additional more variable features include alacrima, achalasia, cataracts, or hepatic steatosis (Liang et al., 2015; Koehler et al., 2017). For a discussion of genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy, see LGMDR1 (253600).
Autosomal recessive limb-girdle muscular dystrophy type 2U
MedGen UID:
1683417
Concept ID:
C5190987
Disease or Syndrome
A rare subtype of autosomal recessive limb-girdle muscular dystrophy disorder with characteristics of infantile to childhood-onset of slowly progressive, principally proximal shoulder and/or pelvic-girdle muscular weakness that typically presents with positive Gowers'' sign and is associated with elevated creatine kinase levels, hyporeflexia, joint and achilles tendon contractures and muscle hypertrophy usually of the thighs, calves and/or tongue. Other highly variable features include cerebellar, cardiac and ocular abnormalities.

Professional guidelines

PubMed

Roy B, Peck A, Evangelista T, Pfeffer G, Wang L, Diaz-Manera J, Korb M, Wicklund MP, Milone M, Freimer M, Kushlaf H, Villar-Quiles RN, Stojkovic T, Needham M, Palmio J, Lloyd TE, Keung B, Mozaffar T, Weihl CC, Kimonis V
Ann Clin Transl Neurol 2023 May;10(5):686-695. Epub 2023 Apr 7 doi: 10.1002/acn3.51760. PMID: 37026610Free PMC Article
Groh WJ, Bhakta D, Tomaselli GF, Aleong RG, Teixeira RA, Amato A, Asirvatham SJ, Cha YM, Corrado D, Duboc D, Goldberger ZD, Horie M, Hornyak JE, Jefferies JL, Kääb S, Kalman JM, Kertesz NJ, Lakdawala NK, Lambiase PD, Lubitz SA, McMillan HJ, McNally EM, Milone M, Namboodiri N, Nazarian S, Patton KK, Russo V, Sacher F, Santangeli P, Shen WK, Sobral Filho DC, Stambler BS, Stöllberger C, Wahbi K, Wehrens XHT, Weiner MM, Wheeler MT, Zeppenfeld K
Heart Rhythm 2022 Oct;19(10):e61-e120. Epub 2022 Apr 29 doi: 10.1016/j.hrthm.2022.04.022. PMID: 35500790
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

Zrelski MM, Kustermann M, Winter L
Cells 2021 Sep 19;10(9) doi: 10.3390/cells10092480. PMID: 34572129Free PMC Article
Silva IS, Pedrosa R, Azevedo IG, Forbes AM, Fregonezi GA, Dourado Junior ME, Lima SR, Ferreira GM
Cochrane Database Syst Rev 2019 Sep 5;9(9):CD011711. doi: 10.1002/14651858.CD011711.pub2. PMID: 31487757Free 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
Fichna JP, Macias A, Piechota M, Korostyński M, Potulska-Chromik A, Redowicz MJ, Zekanowski C
Hum Genomics 2018 Jul 3;12(1):34. doi: 10.1186/s40246-018-0167-1. PMID: 29970176Free PMC Article
Mohassel P, Mammen AL
J Neuromuscul Dis 2018;5(1):11-20. doi: 10.3233/JND-170282. PMID: 29480216Free PMC Article

Diagnosis

Groh WJ, Bhakta D, Tomaselli GF, Aleong RG, Teixeira RA, Amato A, Asirvatham SJ, Cha YM, Corrado D, Duboc D, Goldberger ZD, Horie M, Hornyak JE, Jefferies JL, Kääb S, Kalman JM, Kertesz NJ, Lakdawala NK, Lambiase PD, Lubitz SA, McMillan HJ, McNally EM, Milone M, Namboodiri N, Nazarian S, Patton KK, Russo V, Sacher F, Santangeli P, Shen WK, Sobral Filho DC, Stambler BS, Stöllberger C, Wahbi K, Wehrens XHT, Weiner MM, Wheeler MT, Zeppenfeld K
Heart Rhythm 2022 Oct;19(10):e61-e120. Epub 2022 Apr 29 doi: 10.1016/j.hrthm.2022.04.022. PMID: 35500790
Vainzof M, Souza LS, Gurgel-Giannetti J, Zatz M
Neuromuscul Disord 2021 Oct;31(10):1021-1027. Epub 2021 Jul 28 doi: 10.1016/j.nmd.2021.07.014. PMID: 34404573
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
Fichna JP, Macias A, Piechota M, Korostyński M, Potulska-Chromik A, Redowicz MJ, Zekanowski C
Hum Genomics 2018 Jul 3;12(1):34. doi: 10.1186/s40246-018-0167-1. PMID: 29970176Free PMC Article
Mathews KD, Moore SA
Curr Neurol Neurosci Rep 2003 Jan;3(1):78-85. doi: 10.1007/s11910-003-0042-9. PMID: 12507416

Therapy

Morales-Rosado JA, Schwab TL, Macklin-Mantia SK, Foley AR, Pinto E Vairo F, Pehlivan D, Donkervoort S, Rosenfeld JA, Boyum GE, Hu Y, Cong ATQ, Lotze TE, Mohila CA, Saade D, Bharucha-Goebel D, Chao KR, Grunseich C, Bruels CC, Littel HR, Estrella EA, Pais L, Kang PB, Zimmermann MT, Lupski JR, Lee B, Schellenberg MJ, Clark KJ, Wierenga KJ, Bönnemann CG, Klee EW
Am J Hum Genet 2023 Jun 1;110(6):989-997. Epub 2023 May 10 doi: 10.1016/j.ajhg.2023.04.006. PMID: 37167966Free PMC Article
Yogev Y, Shorer Z, Koifman A, Wormser O, Drabkin M, Halperin D, Dolgin V, Proskorovski-Ohayon R, Hadar N, Davidov G, Nudelman H, Zarivach R, Shelef I, Perez Y, Birk OS
Proc Natl Acad Sci U S A 2023 Feb 14;120(7):e2217831120. Epub 2023 Feb 6 doi: 10.1073/pnas.2217831120. PMID: 36745799Free PMC Article
Silva IS, Pedrosa R, Azevedo IG, Forbes AM, Fregonezi GA, Dourado Junior ME, Lima SR, Ferreira GM
Cochrane Database Syst Rev 2019 Sep 5;9(9):CD011711. doi: 10.1002/14651858.CD011711.pub2. PMID: 31487757Free PMC Article
Mendell JR, Chicoine LG, Al-Zaidy SA, Sahenk Z, Lehman K, Lowes L, Miller N, Alfano L, Galliers B, Lewis S, Murrey D, Peterson E, Griffin DA, Church K, Cheatham S, Cheatham J, Hogan MJ, Rodino-Klapac LR
Hum Gene Ther 2019 Jul;30(7):794-801. Epub 2019 Apr 19 doi: 10.1089/hum.2019.006. PMID: 30838895Free PMC Article
Mohassel P, Mammen AL
J Neuromuscul Dis 2018;5(1):11-20. doi: 10.3233/JND-170282. PMID: 29480216Free PMC Article

Prognosis

Kashyap N, Nikhanj A, Labib D, Prosia E, Rivest S, Flewitt J, Pfeffer G, Bakal JA, Siddiqi ZA, Coulden RA, Thompson R, White JA, Oudit GY
J Am Heart Assoc 2023 Nov 7;12(21):e030229. Epub 2023 Nov 6 doi: 10.1161/JAHA.123.030229. PMID: 37929714Free PMC Article
Silva IS, Pedrosa R, Azevedo IG, Forbes AM, Fregonezi GA, Dourado Junior ME, Lima SR, Ferreira GM
Cochrane Database Syst Rev 2019 Sep 5;9(9):CD011711. doi: 10.1002/14651858.CD011711.pub2. PMID: 31487757Free PMC Article
Mendell JR, Chicoine LG, Al-Zaidy SA, Sahenk Z, Lehman K, Lowes L, Miller N, Alfano L, Galliers B, Lewis S, Murrey D, Peterson E, Griffin DA, Church K, Cheatham S, Cheatham J, Hogan MJ, Rodino-Klapac LR
Hum Gene Ther 2019 Jul;30(7):794-801. Epub 2019 Apr 19 doi: 10.1089/hum.2019.006. PMID: 30838895Free PMC Article
Cotta A, Carvalho E, da-Cunha-Júnior AL, Paim JF, Navarro MM, Valicek J, Menezes MM, Nunes SV, Xavier Neto R, Takata RI, Vargas AP
Arq Neuropsiquiatr 2014 Sep;72(9):721-34. doi: 10.1590/0004-282x20140110. PMID: 25252238
Bushby KM
Baillieres Clin Neurol 1994 Aug;3(2):407-30. PMID: 7952855

Clinical prediction guides

Reelfs AM, Stephan CM, Mockler SRH, Laubscher KM, Zimmerman MB, Mathews KD
Neuromuscul Disord 2023 Jun;33(6):523-530. Epub 2023 May 19 doi: 10.1016/j.nmd.2023.05.005. PMID: 37247532Free PMC Article
de Bruyn A, Montagnese F, Holm-Yildiz S, Scharff Poulsen N, Stojkovic T, Behin A, Palmio J, Jokela M, De Bleecker JL, de Visser M, van der Kooi AJ, Ten Dam L, Domínguez González C, Maggi L, Gallone A, Kostera-Pruszczyk A, Macias A, Łusakowska A, Nedkova V, Olive M, Álvarez-Velasco R, Wanschitz J, Paradas C, Mavillard F, Querin G, Fernández-Eulate G, Quinlivan R, Walter MC, Depuydt CE, Udd B, Vissing J, Schoser B, Claeys KG
Brain 2023 Sep 1;146(9):3800-3815. doi: 10.1093/brain/awad088. PMID: 36913258
Silva IS, Pedrosa R, Azevedo IG, Forbes AM, Fregonezi GA, Dourado Junior ME, Lima SR, Ferreira GM
Cochrane Database Syst Rev 2019 Sep 5;9(9):CD011711. doi: 10.1002/14651858.CD011711.pub2. PMID: 31487757Free PMC Article
Mendell JR, Chicoine LG, Al-Zaidy SA, Sahenk Z, Lehman K, Lowes L, Miller N, Alfano L, Galliers B, Lewis S, Murrey D, Peterson E, Griffin DA, Church K, Cheatham S, Cheatham J, Hogan MJ, Rodino-Klapac LR
Hum Gene Ther 2019 Jul;30(7):794-801. Epub 2019 Apr 19 doi: 10.1089/hum.2019.006. PMID: 30838895Free PMC Article
Gavassini BF, Carboni N, Nielsen JE, Danielsen ER, Thomsen C, Svenstrup K, Bello L, Maioli MA, Marrosu G, Ticca AF, Mura M, Marrosu MG, Soraru G, Angelini C, Vissing J, Pegoraro E
Muscle Nerve 2011 Nov;44(5):703-9. Epub 2011 Sep 26 doi: 10.1002/mus.22132. PMID: 21953594

Recent systematic reviews

Audhya IF, Cheung A, Szabo SM, Flint E, Weihl CC, Gooch KL
J Neuromuscul Dis 2022;9(4):477-492. doi: 10.3233/JND-210771. PMID: 35527561Free PMC Article
Fermon C, Authier FJ, Gallay L
Neuromuscul Disord 2022 Feb;32(2):116-124. Epub 2021 Oct 14 doi: 10.1016/j.nmd.2021.10.003. PMID: 34980535
Salvati A, Bonaventura E, Sesso G, Pasquariello R, Sicca F
Seizure 2021 Oct;91:425-436. Epub 2021 Jul 21 doi: 10.1016/j.seizure.2021.07.020. PMID: 34325301
Silva IS, Pedrosa R, Azevedo IG, Forbes AM, Fregonezi GA, Dourado Junior ME, Lima SR, Ferreira GM
Cochrane Database Syst Rev 2019 Sep 5;9(9):CD011711. doi: 10.1002/14651858.CD011711.pub2. PMID: 31487757Free PMC Article
Mah JK, Korngut L, Fiest KM, Dykeman J, Day LJ, Pringsheim T, Jette N
Can J Neurol Sci 2016 Jan;43(1):163-77. doi: 10.1017/cjn.2015.311. PMID: 26786644

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