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Late-onset proximal muscle weakness

MedGen UID:
871110
Concept ID:
C4025578
Finding
Synonym: Proximal muscle weakness (later-onset)
 
HPO: HP:0003694

Definition

Lack of strength of the proximal musculature occurring late in the clinical course. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVLate-onset proximal muscle weakness

Conditions with this feature

Desmin-related myofibrillar myopathy
MedGen UID:
330449
Concept ID:
C1832370
Disease or Syndrome
Myofibrillar myopathy (MFM) is a noncommittal term that refers to a group of morphologically homogeneous, but genetically heterogeneous chronic neuromuscular disorders. The morphologic changes in skeletal muscle in MFM result from disintegration of the sarcomeric Z disc and the myofibrils, followed by abnormal ectopic accumulation of multiple proteins involved in the structure of the Z disc, including desmin, alpha-B-crystallin (CRYAB; 123590), dystrophin (300377), and myotilin (TTID; 604103). Genetic Heterogeneity of Myofibrillar Myopathy Other forms of MFM include MFM2 (608810), caused by mutation in the CRYAB gene (123590); MFM3 (609200), caused by mutation in the MYOT gene (604103); MFM4 (609452), caused by mutation in the ZASP gene (LDB3; 605906); MFM5 (609524), caused by mutation in the FLNC gene (102565); MFM6 (612954), caused by mutation in the BAG3 gene (603883); MFM7 (617114), caused by mutation in the KY gene (605739); MFM8 (617258), caused by mutation in the PYROXD1 gene (617220); MFM9 (603689), caused by mutation in the TTN gene (188840); MFM10 (619040), caused by mutation in the SVIL UNC45B gene (611220); MFM11 (619178), caused by mutation in the UNC45B gene (611220); and MFM12 (619424), caused by mutation in the MYL2 gene (160781). 'Desmin-related myopathy' is another term referring to MFM in which there are intrasarcoplasmic aggregates of desmin, usually in addition to other sarcomeric proteins. Rigid spine syndrome (602771), caused by mutation in the SEPN1 gene (606210), is another desmin-related myopathy. Goebel (1995) provided a review of desmin-related myopathy.
Myofibrillar myopathy 2
MedGen UID:
324735
Concept ID:
C1837317
Disease or Syndrome
Alpha-B crystallin-related myofibrillar myopathy is an autosomal dominant muscular disorder characterized by adult onset of progressive muscle weakness affecting both the proximal and distal muscles and associated with respiratory insufficiency, cardiomyopathy, and cataracts. There is phenotypic variability both within and between families (Fardeau et al., 1978; Selcen and Engel, 2003). A homozygous founder mutation in the CRYAB gene has been identified in Canadian aboriginal infants of Cree origin who have a severe fatal infantile hypertonic form of myofibrillar myopathy; see 613869. For a phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (601419).
Finnish upper limb-onset distal myopathy
MedGen UID:
400595
Concept ID:
C1864706
Disease or Syndrome
Distal myopathy-3 (MPD3) is an autosomal dominant skeletal muscle disorder characterized by adult onset of slowly progressive distal muscular weakness and atrophy affecting the upper and lower limbs, leading to difficulties using the hands and walking difficulties. Proximal muscle involvement may occur later in the disease, but patients typically remain ambulatory. Muscle biopsy shows myopathic changes with rimmed vacuoles (Hackman et al., 2021).

Professional guidelines

PubMed

Meznaric M, Fumic K, Leonardis L
J Clin Pathol 2019 Jul;72(7):468-472. Epub 2019 Mar 16 doi: 10.1136/jclinpath-2018-205446. PMID: 30878973
Boentert M, Prigent H, Várdi K, Jones HN, Mellies U, Simonds AK, Wenninger S, Barrot Cortés E, Confalonieri M
Int J Mol Sci 2016 Oct 17;17(10) doi: 10.3390/ijms17101735. PMID: 27763517Free PMC Article
Harish P, Malerba A, Dickson G, Bachtarzi H
Hum Gene Ther 2015 May;26(5):286-92. Epub 2015 May 11 doi: 10.1089/hum.2015.014. PMID: 25860803

Recent clinical studies

Etiology

Ranta-Aho J, Johari M, Udd B
Curr Opin Neurol 2024 Oct 1;37(5):515-522. Epub 2024 Jul 16 doi: 10.1097/WCO.0000000000001299. PMID: 39017652Free PMC Article
Sivera R, Pelayo-Negro AL, Jericó I, Domínguez-González C, Horga A, Rodriguez De Rivera FJ, Gallardo E, Tembl JI, Bermejo-Guerrero L, Pagola Lorz MI, Azorín I, Cordoba M, Fenollar-Cortés MDM, Millet E, Vilchez JJ, Espinós C, Apellániz-Ruiz M, Sevilla T
Neurology 2024 Apr 9;102(7):e209174. Epub 2024 Mar 21 doi: 10.1212/WNL.0000000000209174. PMID: 38513194
Boentert M, Prigent H, Várdi K, Jones HN, Mellies U, Simonds AK, Wenninger S, Barrot Cortés E, Confalonieri M
Int J Mol Sci 2016 Oct 17;17(10) doi: 10.3390/ijms17101735. PMID: 27763517Free PMC Article
Udd B
Handb Clin Neurol 2011;101:239-62. doi: 10.1016/B978-0-08-045031-5.00016-5. PMID: 21496636
Johnston W, Karpati G, Carpenter S, Arnold D, Shoubridge EA
Ann Neurol 1995 Jan;37(1):16-23. doi: 10.1002/ana.410370106. PMID: 7818252

Diagnosis

Smith IC, Chakraborty S, Bourque PR, Sampaio ML, Melkus G, Lochmüller H, Woulfe J, Parks RJ, Brais B, Warman-Chardon J
Neuromuscul Disord 2023 Nov;33(11):824-834. Epub 2023 Oct 6 doi: 10.1016/j.nmd.2023.09.010. PMID: 37926637
Nicolau S, Milone M
Curr Neurol Neurosci Rep 2023 Nov;23(11):777-784. Epub 2023 Oct 19 doi: 10.1007/s11910-023-01311-0. PMID: 37856049
Schnitzler LJ, Schreckenbach T, Nadaj-Pakleza A, Stenzel W, Rushing EJ, Van Damme P, Ferbert A, Petri S, Hartmann C, Bornemann A, Meisel A, Petersen JA, Tousseyn T, Thal DR, Reimann J, De Jonghe P, Martin JJ, Van den Bergh PY, Schulz JB, Weis J, Claeys KG
Orphanet J Rare Dis 2017 May 11;12(1):86. doi: 10.1186/s13023-017-0640-2. PMID: 28490364Free PMC Article
Boentert M, Prigent H, Várdi K, Jones HN, Mellies U, Simonds AK, Wenninger S, Barrot Cortés E, Confalonieri M
Int J Mol Sci 2016 Oct 17;17(10) doi: 10.3390/ijms17101735. PMID: 27763517Free PMC Article
Udd B
Handb Clin Neurol 2011;101:239-62. doi: 10.1016/B978-0-08-045031-5.00016-5. PMID: 21496636

Therapy

Tan L, Zschüntzsch J, Meyer S, Stobbe A, Bruex H, Regensburger AP, Claßen M, Alves F, Jüngert J, Rother U, Li Y, Danko V, Lang W, Türk M, Schmidt S, Vorgerd M, Schlaffke L, Woelfle J, Hahn A, Mensch A, Winterholler M, Trollmann R, Heiß R, Wagner AL, Raming R, Knieling F
Nat Commun 2024 Sep 8;15(1):7843. doi: 10.1038/s41467-024-52143-6. PMID: 39245687Free PMC Article
Avanti M, Martin A, Columbres RC, Mozaffar T, Kimonis V
Mol Genet Metab 2023 Nov;140(3):107644. Epub 2023 Jun 28 doi: 10.1016/j.ymgme.2023.107644. PMID: 37515933
Wen B, Tang S, Lv X, Li D, Xu J, Olsen RKJ, Zhao Y, Li W, Wang T, Shao K, Zhao D, Yan C
Hum Mol Genet 2022 Mar 31;31(7):1115-1129. doi: 10.1093/hmg/ddab308. PMID: 34718578
Moriggi M, Capitanio D, Torretta E, Barbacini P, Bragato C, Sartori P, Moggio M, Maggi L, Mora M, Gelfi C
Int J Mol Sci 2021 Mar 11;22(6) doi: 10.3390/ijms22062850. PMID: 33799647Free PMC Article
Chan J, Desai AK, Kazi ZB, Corey K, Austin S, Hobson-Webb LD, Case LE, Jones HN, Kishnani PS
Mol Genet Metab 2017 Mar;120(3):163-172. Epub 2016 Dec 11 doi: 10.1016/j.ymgme.2016.12.004. PMID: 28185884

Prognosis

Smith IC, Chakraborty S, Bourque PR, Sampaio ML, Melkus G, Lochmüller H, Woulfe J, Parks RJ, Brais B, Warman-Chardon J
Neuromuscul Disord 2023 Nov;33(11):824-834. Epub 2023 Oct 6 doi: 10.1016/j.nmd.2023.09.010. PMID: 37926637
Lillback V, Savarese M, Sandholm N, Hackman P, Udd B
Eur J Neurol 2023 Apr;30(4):1080-1088. Epub 2023 Feb 8 doi: 10.1111/ene.15688. PMID: 36692225
Wen B, Tang S, Lv X, Li D, Xu J, Olsen RKJ, Zhao Y, Li W, Wang T, Shao K, Zhao D, Yan C
Hum Mol Genet 2022 Mar 31;31(7):1115-1129. doi: 10.1093/hmg/ddab308. PMID: 34718578
Monforte M, Primiano G, Silvestri G, Mirabella M, Luigetti M, Cuccagna C, Ricci E, Servidei S, Tasca G
J Neurol 2018 Mar;265(3):542-551. Epub 2018 Jan 22 doi: 10.1007/s00415-018-8741-y. PMID: 29356967
Verschueren A
Rev Neurol (Paris) 2017 May;173(5):320-325. Epub 2017 Apr 20 doi: 10.1016/j.neurol.2017.03.018. PMID: 28434507

Clinical prediction guides

Tan L, Zschüntzsch J, Meyer S, Stobbe A, Bruex H, Regensburger AP, Claßen M, Alves F, Jüngert J, Rother U, Li Y, Danko V, Lang W, Türk M, Schmidt S, Vorgerd M, Schlaffke L, Woelfle J, Hahn A, Mensch A, Winterholler M, Trollmann R, Heiß R, Wagner AL, Raming R, Knieling F
Nat Commun 2024 Sep 8;15(1):7843. doi: 10.1038/s41467-024-52143-6. PMID: 39245687Free PMC Article
Wen B, Tang S, Lv X, Li D, Xu J, Olsen RKJ, Zhao Y, Li W, Wang T, Shao K, Zhao D, Yan C
Hum Mol Genet 2022 Mar 31;31(7):1115-1129. doi: 10.1093/hmg/ddab308. PMID: 34718578
De Vito EL, Arce SC, Monteiro SG, Vaca Ruiz GA
Neuromuscul Disord 2019 Jun;29(6):444-447. Epub 2019 Mar 21 doi: 10.1016/j.nmd.2019.03.008. PMID: 31130377
Rajakulendran S, Parton M, Holton JL, Hanna MG
Muscle Nerve 2011 Oct;44(4):590-3. doi: 10.1002/mus.22196. PMID: 21922472
Johnston W, Karpati G, Carpenter S, Arnold D, Shoubridge EA
Ann Neurol 1995 Jan;37(1):16-23. doi: 10.1002/ana.410370106. PMID: 7818252

Recent systematic reviews

Finsterer J
J Clin Neuromuscul Dis 2023 Mar 1;24(3):140-146. doi: 10.1097/CND.0000000000000422. PMID: 36809201
Maulet T, Bonnyaud C, Weill C, Laforêt P, Cattagni T
Neurology 2023 Jan 3;100(1):e72-e83. Epub 2022 Oct 27 doi: 10.1212/WNL.0000000000201333. PMID: 36302669
Chan J, Desai AK, Kazi ZB, Corey K, Austin S, Hobson-Webb LD, Case LE, Jones HN, Kishnani PS
Mol Genet Metab 2017 Mar;120(3):163-172. Epub 2016 Dec 11 doi: 10.1016/j.ymgme.2016.12.004. PMID: 28185884
Gerami P, Schope JM, McDonald L, Walling HW, Sontheimer RD
J Am Acad Dermatol 2006 Apr;54(4):597-613. Epub 2006 Jan 23 doi: 10.1016/j.jaad.2005.10.041. PMID: 16546580

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