User:Lukelahood/Myofibrillar myopathy
| Myofibrillar myopathy | |
|---|---|
| Other names | Myofibrillar myopathies |
| Specialty | Neurology, Neuromuscular medicine |
| Symptoms | Weakness |
| Duration | Lifelong |
| Causes | Genetic mutation |
| Diagnostic method | Genetic testing, muscle biopsy |
Myofibrillar myopathy (MFM) is a group of genetic muscle diseases that cause weakness. MFM is distinguished from other genetic muscles diseases by characteristic microscopic findings of muscle.
Signs and symptoms[edit]
The various myofibrillary myopathies can result in one of several constellation of signs and symptoms, termed phenotype. These include limb-girdle muscular dystrophy, distal myopathy, scapuloperoneal syndrome or rigid spine syndrome.
In 75% of cases, MFM preferentially weakens the distal muscles, or those of the hands and feet. Otherwise, a the proximal muscles are preferentially affected, a limb-girdle distribution.[1]
- Respiratory failure
- Cardiomyopathy
Cause[edit]
Each MFM subtype is genetic and defined by the mutated gene. With most genetic disorders, it can be inherited or sporadic. Once a sporadic case occurs, it can then be passed on to future generations. Typically, MFMs are inherited in an autosomal dominant pattern, meaning one mutation is sufficient to cause disease, and each child of an affected parent has a 50% of inheriting the gene and disease.
| Type | Name | Inheritance | OMIM | Gene | Protein function | Gene also implicated in: | Notes |
|---|---|---|---|---|---|---|---|
| MFM1 | Desminopathy[2]
Myofibrillar with arrhythmogenic right ventricular cardiomyopathy[3] |
AD,AR | 601419 | DES | Intermediate filament that interconnects Z-disk, sarcolemma, nucleus, and mitochondria.[2] Also found in intercalated discs and Purkinje fibers of cardiac muscle.[2] | ||
| MFM2 | αB-Crystallinopathy[2] | AD | 608810 | CRYAB | Heat-shock protein with molecular chaperone-like properties[2][4] | ||
| MFM3 | Myotilinopathy[2] | AD | 609200 | MYOT | Binds to alpha-actinin and filamin C. Alpha-actinin is the main component of the Z-disk.[2] Not prominent in cardiac muscle.[2] | ||
| MFM4 | Zaspopathy[2] | AD | 609452 | LDB3 | Sarcomere stabilization | ||
| MFM5 | Filamin C[3] | AD | 609524 | FLNC | Cytoskeletal protein found at peripheral Z-disk and subsarcolemma.[2] Responsible for organizing actin filaments, stabilizing the sarcolemma, and being a scaffold for signaling proteins.[2] | ||
| MFM6 | BAG3opathy[2] | AD | 612954 | BAG3 | Bag3 (Bcl-2 associated athanogene 3) is found in skeletal and cardiac muscle.[2] It is a Co-chaperone, interacting with heat shock protein 70.[2] It is involved with several antiapoptotic pathways.[2] | ||
| MFM7 | AR | 617114 | KY | Interacts with other proteins | |||
| MFM8 | AR | 617258 | PYROXD1 | Oxidoreductase, possibly involved in energy metabolism.[5] | |||
| MFM9 | Congenital muscular dystrophy with desmin inclusions[3] | AD | 603689 | TTN | Sarcomere protein that connects myosin to Z-disk, acting as a molecular spring. | ||
| MFM10 | AR | 619040 | SVIL | Actin-binding protein, also associated with plasma membranes, possibly acting as a link between the two in skeletal and cardiac muscle.[6] | |||
| MFM11 | AR | 619178 | UNC45B | Myosin-specific chaperone, working with hsp70 and hsp 90, which plays a role in assembling skeletal and cardiac muscle. | |||
| MFM12 | AR | 619424 | MYL2 | Myosin regulatory light chain 2 regulates myosin ATPase activity in smooth muscle, skeletal muscle, and cardiac muscle. | |||
| Scapuloperoneal[3] | |||||||
| MFM = myofibrillary myopathy; AD = autosomal dominant; AR = autosomal recessive | |||||||
Pathophysiology[edit]
As the name suggests, myofibrillar myopathy causes damage to myofibrils,[1] the rod-shaped components of the cells that make up muscles. Myofibrils are composed of repeating protein structures, called sarcomeres, that are responsible for muscle contraction. Each sarcomere is made up of actin, myosin, and other proteins. The actin is bound together at the Z-disc. The genes implicated in MFM code for proteins founds in the sarcomere, the structural framework (cytoskeleton) outside of the sarcomere, and protein quality control systems.[7]
MFM causes myofibril damage.[1] The first sign is disintegration of the Z-disk region.[1] Subsequently, there is accumulation of degraded proteins in the areas around myofibrils.[1]
Diagnosis[edit]
Genetic testing.
Muscle biopsy.
Management[edit]
No disease modifying therapeutics are known as of 2016.[7]
History[edit]
Discovered in
- ^ a b c d e Fichna, JP; Maruszak, A; Żekanowski, C (November 2018). "Myofibrillar myopathy in the genomic context". Journal of applied genetics. 59 (4): 431–439. doi:10.1007/s13353-018-0463-4. PMID 30203143.
- ^ a b c d e f g h i j k l m n o Selcen, D (March 2011). "Myofibrillar myopathies". Neuromuscular disorders : NMD. 21 (3): 161–71. doi:10.1016/j.nmd.2010.12.007. PMID 21256014.
- ^ a b c d Dimachkie, MM; Barohn, RJ (August 2014). "Distal myopathies". Neurologic clinics. 32 (3): 817–42, x. doi:10.1016/j.ncl.2014.04.004. PMID 25037092.
- ^ Augusteyn, RC (November 2004). "alpha-crystallin: a review of its structure and function". Clinical & experimental optometry. 87 (6): 356–66. doi:10.1111/j.1444-0938.2004.tb03095.x. PMID 15575808.
- ^ Lornage, X; Schartner, V; Balbueno, I; Biancalana, V; Willis, T; Echaniz-Laguna, A; Scheidecker, S; Quinlivan, R; Fardeau, M; Malfatti, E; Lannes, B; Sewry, C; Romero, NB; Laporte, J; Böhm, J (27 August 2019). "Clinical, histological, and genetic characterization of PYROXD1-related myopathy". Acta neuropathologica communications. 7 (1): 138. doi:10.1186/s40478-019-0781-8. PMID 31455395.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Pope, RK; Pestonjamasp, KN; Smith, KP; Wulfkuhle, JD; Strassel, CP; Lawrence, JB; Luna, EJ (15 September 1998). "Cloning, characterization, and chromosomal localization of human superillin (SVIL)". Genomics. 52 (3): 342–51. doi:10.1006/geno.1998.5466. PMID 9867483.
- ^ a b Kley, RA; Olivé, M; Schröder, R (October 2016). "New aspects of myofibrillar myopathies". Current opinion in neurology. 29 (5): 628–34. doi:10.1097/WCO.0000000000000357. PMID 27389816.