What is Myostatin Related Hypertrophy?
Myostatin-Related Muscle Hypertrophy, also known as muscle hypertrophy syndrome [1], is a genetic disease caused by mutations in the MSTN gene. When expressed, the MSTN gene codes for a protein, myostatin [2], that regulates muscle growth in utero and throughout life [3]. Myostatin regulates muscle growth by stopping the differentiation of immature muscle cells into mature skeletal muscle. People with Myostatin-Related Muscle Hypertrophy can have up to twice the normal amount of muscle expressed by people without this mutation and tend to have a lower percent body fat because of this. Not only is there more muscle present throughout the body, but the muscle also exhibits greater overall strength [4]. Other than these few symptoms, people affected by this syndrome are of normal intelligence, brain function, have virtually no other associative health issues and live a relatively normal life [2]. However, it should be noted that there are few studies that examine the significance of Myostatin-Related Muscle Hypertrophy's mechanism and it's effects on other body systems such as vascular, cardiac and pulmonary.
Figure 1. Muscle mass increase occurs in children as young as 7 months
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Figure 2. MSTN gene
MSTNThe MSTN gene is located on the shorter end of the second chromosome (2q32.2) [5]. MSTN codes for a protein, myostatin, that is a part of a signaling family called TGF- β [6]. Myostatin is produced as two, unactivated subunits and becomes activated when a protease cleaves the protein. The activated protein is then free to bind with activin type ll receptors that send signals our to recruit co-receptors Alk-3 or Alk-4. The recruitment of these co-receptors causes a cell signaling cascade in muscles that prevent myoblasts from differentiating and becoming mature muscle fibers [7, 8]. A kinase called Akt can also be inhibited by myostatin, which can stimulate protein synthesis [9]. Because myostatin works on inhibing both of these factors, when there is a mutation in the gene and the protein is unable to function, growth of muscle is virtually uncontrolled, thus resulting in increased muscle mass.
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Figure 3. Showing the location of MSTN on the second chromosome
Diagnosis and Testing
Because the frequency of this disease is so low, there is no confirmed prevalence of Myostatin-Related Muscle Hypertrophy [2]. However, it is relatively easy to diagnose. Due to the obvious symptoms of Myostatin-Related Muscle Hypertrophy, clinicians can determine if further testing is needed. Diagnosis usually happens within the first five years of life. Non-invasive procedures include ultrasound, DEXA or MRI. All of these can precisely measure the muscle content – which should be several deviations above the average. You can definitively confirm the disease through sequence analysis of a DNA sample. Because a mutation in MSTN is the only known gene that causes Myostatin-Related Muscle Hypertrophy, if a mutation is found, the syndrome is confirmed [10].
Resources
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References
[1] myostatin-related muscle hypertrophy - Genetics Home Reference
https://ghr.nlm.nih.gov/condition/myostatin-related-muscle-hypertrophy#synonyms [2] myostatin-related muscle hypertrophy - Genetics Home Reference https://ghr.nlm.nih.gov/condition/myostatin-related-muscle-hypertrophy# [3] Medical Definition of Myostatin http://www.medicinenet.com/script/main/art.asp?articlekey=33546 [4] https://rarediseases.info.nih.gov/diseases/10238/myostatin-related-muscle-hypertrophy [5] MSTN - Gene - NCBI https://www.ncbi.nlm.nih.gov/gene?Cmd=DetailsSearch&Term=2660+ed-muscle-hypertrophy [6] http://www.pnas.org/content/104/6/1835.long [7] growth/differentiation factor 8 preproprotein [Homo sapiens] - Protein - NCBI http://www.ncbi.nlm.nih.gov/protein/NP_005250.1 [8] Developmental roles of the BMP1/TLD metalloproteinases. https://www.ncbi.nlm.nih.gov/pubmed/16622848 [9] TGFβ and BMP signaling in skeletal muscle: potential significance for muscle-related disease. https://www.ncbi.nlm.nih.gov/pubmed/25042839 [10] Myostatin-Related Muscle Hypertrophy Kathryn Wagner - https://www.ncbi.nlm.nih.gov/books/NBK1498/ |
Figures
[1] http://forum.mmajunkie.com/forum/threads/rare-medical-condition-gives-toddler-super-strength.12070/
[2] http://forum.mmajunkie.com/forum/threads/rare-medical-condition-gives-toddler-super-strength.12070/ [3] https://ghr.nlm.nih.gov/gene/MSTN |