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Myofibrillar myopathy 11(MFM11)

MedGen UID:
1782465
Concept ID:
C5543038
Disease or Syndrome
Synonym: MYOPATHY, CONGENITAL, WITH ECCENTRIC CORES
 
Gene (location): UNC45B (17q12)
 
Monarch Initiative: MONDO:0030927
OMIM®: 619178

Definition

Myofibrillar myopathy-11 (MFM11) is an autosomal recessive skeletal muscle disorder characterized by onset of slowly progressive proximal muscle weakness in the first decade of life. Some patients may present at birth with hypotonia and feeding difficulties, whereas others present later in mid-childhood. Although most patients show delayed walking at 2 to 3 years, all remain ambulatory into adulthood. More variable features may include decreased respiratory forced vital capacity, variable cardiac features, and calf hypertrophy. Skeletal muscle biopsy shows myopathic changes with variation in fiber size, type 1 fiber predominance, centralized nuclei, eccentrically placed core-like lesions, and distortion of the myofibrillary pattern with Z-line streaming and abnormal myofibrillar aggregates or inclusions (summary by Donkervoort et al., 2020). For a phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (601419). [from OMIM]

Clinical features

From HPO
Fatigue
MedGen UID:
41971
Concept ID:
C0015672
Sign or Symptom
A subjective feeling of tiredness characterized by a lack of energy and motivation.
Shoulder girdle muscle atrophy
MedGen UID:
339837
Concept ID:
C1847766
Finding
Amyotrophy affecting the muscles of the shoulder girdle.
Coarctation of aorta
MedGen UID:
1617
Concept ID:
C0003492
Congenital Abnormality
Coarctation of the aorta is a narrowing or constriction of a segment of the aorta.
Overweight
MedGen UID:
105424
Concept ID:
C0497406
Finding
Increased body weight with a body mass index of 25-29.9 kg per square meter.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Gowers sign
MedGen UID:
65865
Concept ID:
C0234182
Finding
A phenomenon whereby patients are not able to stand up without the use of the hands owing to weakness of the proximal muscles of the lower limbs.
Generalized amyotrophy
MedGen UID:
234650
Concept ID:
C1389113
Disease or Syndrome
Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles.
Centrally nucleated skeletal muscle fibers
MedGen UID:
330782
Concept ID:
C1842170
Finding
An abnormality in which the nuclei of sarcomeres take on an abnormally central localization (or in which this feature is found in an increased proportion of muscle cells).
Calf muscle hypertrophy
MedGen UID:
335868
Concept ID:
C1843057
Finding
Muscle hypertrophy affecting the calf muscles.
Axial muscle weakness
MedGen UID:
334472
Concept ID:
C1843697
Finding
Reduced strength of the axial musculature (i.e., of the muscles of the head and neck, spine, and ribs).
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.
Type 1 muscle fiber predominance
MedGen UID:
344274
Concept ID:
C1854387
Finding
An abnormal predominance of type I muscle fibers (in general, this feature can only be observed on muscle biopsy).
Z-band streaming
MedGen UID:
480908
Concept ID:
C3279278
Finding
Streaming or smearing of the Z band, which is then no longer confined to a narrow zone which bisects the I band. The Z disk may extend across the I band or the entire sarcomere in a zigzag manner. Focal thickening, smudging, and blurring of the Z band takes place concurrently. Myofibrillar disorganization is a frequent but not invariable accompanying change.
EMG: myopathic abnormalities
MedGen UID:
867362
Concept ID:
C4021726
Pathologic Function
The presence of abnormal electromyographic patterns indicative of myopathy, such as small-short polyphasic motor unit potentials.
Muscle fiber granulofilamentous inclusion bodies
MedGen UID:
1842077
Concept ID:
C5826545
Finding
The presence of inclusion bodies within the cytoplasm of muscle cells that contain a mxiture of granules and filaments.
Reduced forced vital capacity
MedGen UID:
337630
Concept ID:
C1846678
Finding
An abnormal reduction in the amount of air a person can expel following maximal inspiration.
Hypernasal speech
MedGen UID:
99115
Concept ID:
C0454555
Finding
A type of speech characterized by the presence of an abnormally increased nasal airflow during speech associated with structural abnormality of the nasal passages.
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.

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

Recent clinical studies

Etiology

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
Vincent AE, Grady JP, Rocha MC, Alston CL, Rygiel KA, Barresi R, Taylor RW, Turnbull DM
Neuromuscul Disord 2016 Oct;26(10):691-701. Epub 2016 Aug 10 doi: 10.1016/j.nmd.2016.08.004. PMID: 27618136Free PMC Article
Jackson S, Schaefer J, Meinhardt M, Reichmann H
Eur J Neurol 2015 Nov;22(11):1429-35. Epub 2015 Jul 23 doi: 10.1111/ene.12814. PMID: 26204918
Olivé M, Odgerel Z, Martínez A, Poza JJ, Bragado FG, Zabalza RJ, Jericó I, Gonzalez-Mera L, Shatunov A, Lee HS, Armstrong J, Maraví E, Arroyo MR, Pascual-Calvet J, Navarro C, Paradas C, Huerta M, Marquez F, Rivas EG, Pou A, Ferrer I, Goldfarb LG
Neuromuscul Disord 2011 Aug;21(8):533-42. Epub 2011 Jun 14 doi: 10.1016/j.nmd.2011.05.002. PMID: 21676617Free PMC Article
Odgerel Z, Sarkozy A, Lee HS, McKenna C, Rankin J, Straub V, Lochmüller H, Paola F, D'Amico A, Bertini E, Bushby K, Goldfarb LG
Neuromuscul Disord 2010 Jul;20(7):438-42. Epub 2010 Jun 3 doi: 10.1016/j.nmd.2010.05.004. PMID: 20605452Free PMC Article

Diagnosis

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
Shi LY, Liu Y, Hu XF, Li XH, Wu XY, Hu J, Ye CQ, Dai QM, Huang HZ
Clin Chim Acta 2022 Jun 1;531:12-16. Epub 2022 Mar 12 doi: 10.1016/j.cca.2022.03.002. PMID: 35292251
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
Matsumura T, Inoue K, Toyooka K, Inoue M, Iida A, Saito Y, Nishikawa T, Moriuchi K, Beck G, Nishino I, Fujimura H
Neuromuscul Disord 2021 Dec;31(12):1282-1286. Epub 2021 Oct 9 doi: 10.1016/j.nmd.2021.10.002. PMID: 34857437
Kim SJ, Nam SH, Kanwal S, Nam DE, Yoo DH, Chae JH, Suh YL, Chung KW, Choi BO
Genes Genomics 2018 Dec;40(12):1269-1277. Epub 2018 Aug 25 doi: 10.1007/s13258-018-0721-1. PMID: 30145633

Prognosis

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
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

Clinical prediction guides

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
Shi LY, Liu Y, Hu XF, Li XH, Wu XY, Hu J, Ye CQ, Dai QM, Huang HZ
Clin Chim Acta 2022 Jun 1;531:12-16. Epub 2022 Mar 12 doi: 10.1016/j.cca.2022.03.002. PMID: 35292251
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
Odgerel Z, Sarkozy A, Lee HS, McKenna C, Rankin J, Straub V, Lochmüller H, Paola F, D'Amico A, Bertini E, Bushby K, Goldfarb LG
Neuromuscul Disord 2010 Jul;20(7):438-42. Epub 2010 Jun 3 doi: 10.1016/j.nmd.2010.05.004. PMID: 20605452Free PMC Article

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