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Myofibrillar myopathy

MedGen UID:
395532
Concept ID:
C2678065
Disease or Syndrome; Finding; Finding
Synonyms: Myofibrillar Myopathies; Myofibrillar Myopathy
SNOMED CT: Myofibrillar myopathy (699269005)
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.
 
Related genes: LDB3, BAG3, MYOT, FLNC, DES, CRYAB
 
HPO: HP:0003715
Monarch Initiative: MONDO:0018943
OMIM® Phenotypic series: PS601419
Orphanet: ORPHA593

Definition

The signs and symptoms of myofibrillar myopathy vary widely among affected individuals, typically depending on the condition's genetic cause. Most people with this disorder begin to develop muscle weakness (myopathy) in mid-adulthood. However, features of this condition can appear anytime between infancy and late adulthood. Muscle weakness most often begins in the hands and feet (distal muscles), but some people first experience weakness in the muscles near the center of the body (proximal muscles). Other affected individuals develop muscle weakness throughout their body. Facial muscle weakness can cause swallowing and speech difficulties. Muscle weakness worsens over time.

Other signs and symptoms of myofibrillar myopathy can include a weakened heart muscle (cardiomyopathy), muscle pain (myalgia), loss of sensation and weakness in the limbs (peripheral neuropathy), and respiratory failure. Individuals with this condition may have skeletal problems including joint stiffness (contractures) and abnormal side-to-side curvature of the spine (scoliosis). Rarely, people with this condition develop clouding of the lens of the eyes (cataracts).

Myofibrillar myopathy is part of a group of disorders called muscular dystrophies that affect muscle function and cause weakness. Myofibrillar myopathy primarily affects skeletal muscles, which are muscles that the body uses for movement. In some cases, the heart (cardiac) muscle is also affected. [from MedlinePlus Genetics]

Conditions with this feature

Myofibrillar myopathy 5
MedGen UID:
372186
Concept ID:
C1836050
Disease or Syndrome
The signs and symptoms of myofibrillar myopathy vary widely among affected individuals, typically depending on the condition's genetic cause. Most people with this disorder begin to develop muscle weakness (myopathy) in mid-adulthood. However, features of this condition can appear anytime between infancy and late adulthood. Muscle weakness most often begins in the hands and feet (distal muscles), but some people first experience weakness in the muscles near the center of the body (proximal muscles). Other affected individuals develop muscle weakness throughout their body. Facial muscle weakness can cause swallowing and speech difficulties. Muscle weakness worsens over time.\n\nOther signs and symptoms of myofibrillar myopathy can include a weakened heart muscle (cardiomyopathy), muscle pain (myalgia), loss of sensation and weakness in the limbs (peripheral neuropathy), and respiratory failure. Individuals with this condition may have skeletal problems including joint stiffness (contractures) and abnormal side-to-side curvature of the spine (scoliosis). Rarely, people with this condition develop clouding of the lens of the eyes (cataracts).\n\nMyofibrillar myopathy is part of a group of disorders called muscular dystrophies that affect muscle function and cause weakness. Myofibrillar myopathy primarily affects skeletal muscles, which are muscles that the body uses for movement. In some cases, the heart (cardiac) muscle is also affected.
Myopathy, myofibrillar, 9, with early respiratory failure
MedGen UID:
350930
Concept ID:
C1863599
Disease or Syndrome
Hereditary myopathy with early respiratory failure (HMERF) is a slowly progressive myopathy that typically begins in the third to fifth decades of life. The usual presenting findings are gait disturbance relating to distal leg weakness or nocturnal respiratory symptoms due to respiratory muscle weakness. Weakness eventually generalizes and affects both proximal and distal muscles. Most affected individuals require walking aids within a few years of onset; some progress to wheelchair dependence and require nocturnal noninvasive ventilatory support about ten years after onset. The phenotype varies even among individuals within the same family: some remain ambulant until their 70s whereas others may require ventilator support in their 40s.
X-linked scapuloperoneal muscular dystrophy
MedGen UID:
395530
Concept ID:
C2678061
Disease or Syndrome
A rare, genetic, muscular dystrophy disease characterized by the co-occurrence of late onset scapular and peroneal muscle weakness, principally manifesting with distal lower limb and proximal upper limb weakness and scapular winging.
Myofibrillar myopathy 6
MedGen UID:
414119
Concept ID:
C2751831
Disease or Syndrome
Myofibrillar myopathy-6 is an autosomal dominant severe neuromuscular disorder characterized by onset in the first decade of rapidly progressive generalized and proximal muscle weakness, respiratory insufficiency, cardiomyopathy, and skeletal deformities related to muscle weakness. Muscle biopsy shows fiber-type grouping, disruption of the Z lines, and filamentous inclusions, and sural nerve biopsy shows a neuropathy, often with giant axonal neurons. Most patients are severely affected by the second decade and need cardiac transplant, ventilation, and/or a wheelchair (summary by Jaffer et al., 2012). For a phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy (MFM), see MFM1 (601419).
Myofibrillar myopathy 3
MedGen UID:
811509
Concept ID:
C3714934
Disease or Syndrome
Myofibrillar myopathy refers to a genetically heterogeneous group of muscular disorders characterized by a pathologic morphologic pattern of myofibrillar degradation and abnormal accumulation of proteins involved with the sarcomeric Z disc (summary by Foroud et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (601419).
Nemaline myopathy 8
MedGen UID:
815539
Concept ID:
C3809209
Disease or Syndrome
Nemaline myopathy-8 is a severe autosomal recessive muscle disorder characterized by fetal akinesia or hypokinesia, followed by contractures, fractures, respiratory failure, and swallowing difficulties apparent at birth. Most patients die in infancy. Skeletal muscle biopsy shows numerous small nemaline bodies, often with no normal myofibrils (summary by Ravenscroft et al., 2013). For a discussion of genetic heterogeneity of nemaline myopathy, see NEM3 (161800).
Myofibrillar myopathy 4
MedGen UID:
1648314
Concept ID:
C4721886
Disease or Syndrome
Myofibrillar myopathy-4 (MFM4) is an autosomal dominant disorder characterized by adult-onset distal muscle weakness primarily affecting the lower limbs at onset. Affected individuals usually present with gait difficulties in their forties, followed by slow progression with eventual involvement of the hands and proximal muscles of the lower limbs. Rare patients may develop cardiomyopathy. Skeletal muscle biopsy shows myopathic changes with myofibrillar changes (Selcen and Engel, 2005; Griggs et al., 2007). For a phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (601419).

Professional guidelines

PubMed

Valberg SJ, Henry ML, Herrick KL, Velez-Irizarry D, Finno CJ, Petersen JL
Equine Vet J 2023 Mar;55(2):230-238. Epub 2022 Apr 1 doi: 10.1111/evj.13574. PMID: 35288976Free PMC Article
Mair D, Biskup S, Kress W, Abicht A, Brück W, Zechel S, Knop KC, Koenig FB, Tey S, Nikolin S, Eggermann K, Kurth I, Ferbert A, Weis J
Brain Pathol 2020 Sep;30(5):877-896. Epub 2020 Jun 15 doi: 10.1111/bpa.12864. PMID: 32419263Free PMC Article

Recent clinical studies

Etiology

Felice KJ
Neurol Clin 2020 Aug;38(3):637-659. Epub 2020 Jun 11 doi: 10.1016/j.ncl.2020.03.007. PMID: 32703474
Verdonschot JAJ, Vanhoutte EK, Claes GRF, Helderman-van den Enden ATJM, Hoeijmakers JGJ, Hellebrekers DMEI, de Haan A, Christiaans I, Lekanne Deprez RH, Boen HM, van Craenenbroeck EM, Loeys BL, Hoedemaekers YM, Marcelis C, Kempers M, Brusse E, van Waning JI, Baas AF, Dooijes D, Asselbergs FW, Barge-Schaapveld DQCM, Koopman P, van den Wijngaard A, Heymans SRB, Krapels IPC, Brunner HG
Hum Mutat 2020 Jun;41(6):1091-1111. Epub 2020 Mar 20 doi: 10.1002/humu.24004. PMID: 32112656Free PMC Article
Fichna JP, Maruszak A, Żekanowski C
J Appl Genet 2018 Nov;59(4):431-439. Epub 2018 Sep 10 doi: 10.1007/s13353-018-0463-4. PMID: 30203143
Palmio J, Udd B
Rev Neurol (Paris) 2016 Oct;172(10):587-593. Epub 2016 Sep 13 doi: 10.1016/j.neurol.2016.07.019. PMID: 27638134
Selcen D
Neuromuscul Disord 2011 Mar;21(3):161-71. Epub 2011 Jan 20 doi: 10.1016/j.nmd.2010.12.007. PMID: 21256014Free PMC Article

Diagnosis

Savarese M, Sarparanta J, Vihola A, Jonson PH, Johari M, Rusanen S, Hackman P, Udd B
Acta Myol 2020 Dec;39(4):245-265. Epub 2020 Dec 1 doi: 10.36185/2532-1900-028. PMID: 33458580Free PMC Article
Felice KJ
Neurol Clin 2020 Aug;38(3):637-659. Epub 2020 Jun 11 doi: 10.1016/j.ncl.2020.03.007. PMID: 32703474
Dimachkie MM, Barohn RJ
Neurol Clin 2014 Aug;32(3):817-42, x. Epub 2014 May 15 doi: 10.1016/j.ncl.2014.04.004. PMID: 25037092Free PMC Article
Claeys KG, Fardeau M
Handb Clin Neurol 2013;113:1337-42. doi: 10.1016/B978-0-444-59565-2.00005-8. PMID: 23622358
Selcen D
Neuromuscul Disord 2011 Mar;21(3):161-71. Epub 2011 Jan 20 doi: 10.1016/j.nmd.2010.12.007. PMID: 21256014Free PMC Article

Therapy

Loarce-Martos J, Lilleker JB, Parker M, McHugh N, Chinoy H
Rheumatology (Oxford) 2021 Jul 1;60(7):3398-3403. doi: 10.1093/rheumatology/keaa801. PMID: 33367878
Maerkens A, Kley RA, Olivé M, Theis V, van der Ven PF, Reimann J, Milting H, Schreiner A, Uszkoreit J, Eisenacher M, Barkovits K, Güttsches AK, Tonillo J, Kuhlmann K, Meyer HE, Schröder R, Tegenthoff M, Fürst DO, Müller T, Goldfarb LG, Vorgerd M, Marcus K
J Proteomics 2013 Sep 2;90:14-27. Epub 2013 Apr 30 doi: 10.1016/j.jprot.2013.04.026. PMID: 23639843Free PMC Article
Finsterer J, Stöllberger C, Höftberger R
Heart Lung 2011 Sep-Oct;40(5):e123-7. Epub 2011 Apr 9 doi: 10.1016/j.hrtlng.2010.07.016. PMID: 21481933

Prognosis

Xu Y, Liu SX, Xu WB, Luo JM, Niu JW, Liu Z, Gao JM, Wang JL, Dai Y, Wang MZ
Chin Med Sci J 2021 Dec 31;36(4):265-278. doi: 10.24920/003883. PMID: 34986963
Verdonschot JAJ, Vanhoutte EK, Claes GRF, Helderman-van den Enden ATJM, Hoeijmakers JGJ, Hellebrekers DMEI, de Haan A, Christiaans I, Lekanne Deprez RH, Boen HM, van Craenenbroeck EM, Loeys BL, Hoedemaekers YM, Marcelis C, Kempers M, Brusse E, van Waning JI, Baas AF, Dooijes D, Asselbergs FW, Barge-Schaapveld DQCM, Koopman P, van den Wijngaard A, Heymans SRB, Krapels IPC, Brunner HG
Hum Mutat 2020 Jun;41(6):1091-1111. Epub 2020 Mar 20 doi: 10.1002/humu.24004. PMID: 32112656Free PMC Article
Fichna JP, Maruszak A, Żekanowski C
J Appl Genet 2018 Nov;59(4):431-439. Epub 2018 Sep 10 doi: 10.1007/s13353-018-0463-4. PMID: 30203143
Andersen AG, Fornander F, Schrøder HD, Krag T, Straub V, Duno M, Vissing J
Neuromuscul Disord 2018 Sep;28(9):798-801. Epub 2018 Jul 5 doi: 10.1016/j.nmd.2018.06.019. PMID: 30061062
Finsterer J, Stöllberger C
Scand Cardiovasc J 2008 Feb;42(1):9-24. doi: 10.1080/14017430701854953. PMID: 18273731

Clinical prediction guides

Hovhannisyan Y, Li Z, Callon D, Suspène R, Batoumeni V, Canette A, Blanc J, Hocini H, Lefebvre C, El-Jahrani N, Kitsara M, L'honoré A, Kordeli E, Fornes P, Concordet JP, Tachdjian G, Rodriguez AM, Vartanian JP, Béhin A, Wahbi K, Joanne P, Agbulut O
Stem Cell Res Ther 2024 Jan 2;15(1):10. doi: 10.1186/s13287-023-03619-7. PMID: 38167524Free PMC Article
Sellung D, Heil L, Daya N, Jacobsen F, Mertens-Rill J, Zhuge H, Döring K, Piran M, Milting H, Unger A, Linke WA, Kley R, Preusse C, Roos A, Fürst DO, Ven PFMV, Vorgerd M
Cells 2023 May 5;12(9) doi: 10.3390/cells12091321. PMID: 37174721Free PMC Article
Xu Y, Liu SX, Xu WB, Luo JM, Niu JW, Liu Z, Gao JM, Wang JL, Dai Y, Wang MZ
Chin Med Sci J 2021 Dec 31;36(4):265-278. doi: 10.24920/003883. PMID: 34986963
Ruparelia AA, McKaige EA, Williams C, Schulze KE, Fuchs M, Oorschot V, Lacene E, Meregalli M, Lee C, Serrano RJ, Baxter EC, Monro K, Torrente Y, Ramm G, Stojkovic T, Lavoie JN, Bryson-Richardson RJ
Autophagy 2021 Sep;17(9):2494-2510. Epub 2020 Oct 19 doi: 10.1080/15548627.2020.1833500. PMID: 33030392Free PMC Article
Margeta M
Annu Rev Pathol 2020 Jan 24;15:261-285. Epub 2019 Oct 8 doi: 10.1146/annurev-pathmechdis-012419-032618. PMID: 31594457

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