Myostatin-related muscle hypertrophy (MRMH) is a rare genetic disorder with an incomplete autosomal dominant mode of inheritance. It is caused by deletions in the intron of the MSTN gene located on chromosome 2q32.2.
Causative mutations lead to a loss of myostatin function which results in significant skeletal muscle growth accompanied by loss of subcutaneous fat tissue. Characteristic MRMH symptoms are evident at birth. Increased muscle mass in MRMH does not necessarily entail augmented physical strength.
Diagnosis is based on clinical findings and supported by genetic tests. Genetic counseling is advisable due to the familial nature of MRMH.
Myostatin-related muscle hypertrophy (MRMH) develops because of pathological mutations in the MSTN gene on the long arm of chromosome 2  . MRMH has a strong familial component but can also occur sporadically . Heterozygotic carriers of MRMH-associated mutations present with a milder MRMH phenotype than homozygotes, suggesting an incomplete autosomal dominant mode of inheritance .
Myostatin - also called growth/differentiation factor 8 (GDF-8) - downregulates muscle growth in mammals. Loss of myostatin function leads to MRMH, while myostatin overexpression is associated with muscle wasting syndromes  . Skeletal muscle overgrowth in MRMH can lead to an effective doubling of muscle tissue volume with a concomitant loss of subcutaneous fat  . Additionally, infant MRMH patients can also show increased tendon reflexes and congenital stimulus-induced myoclonus, which should resolve spontaneously after a few months .
The effect MRMH-associated muscle growth is still under dispute. While MRMH cases in humans seem to suggest increased physical strength in children , detailed histopathological investigations of myostatin-deficient skeletal muscles have revealed a strong predominance of type IIb muscle fibers with tubular aggregates together with a loss of oxidative capacity due to mitochondrial depletion .
Hence, MRMH should result in faster muscle contraction and relaxation combined with conserved maximum tetanic force generation but also in impaired long-term intramuscular energy production .
Entire Body System
1,271 satisfied customers My 77 yr old dad recently had an echocardiogram that showed my 77 yr old dad recently had an echocardiogram that showed moderate to severe concentric left ventricular hypertrophy with some aortic valve scherosis, mild valve regurgitation [justanswer.com]
[…] mechanism Mitochondrial protein import disorder Mitochondrial pyruvate carrier deficiency Mitochondrial spinocerebellar ataxia with epilepsy Mitochondrial substrate carrier disorder Mitochondrial trifunctional protein deficiency Mitral atresia Mitral regurgitation-deafness-skeletal [orpha.net]
Increased Muscle Mass
Heterozygotes may have increased muscle mass. [ncbi.nlm.nih.gov]
People with a mutation in both copies of the gene in each cell (homozygotes) have significantly increased muscle mass and strength. [en.wikipedia.org]
People with a mutation in both copies of the MSTN gene in each cell (homozygotes) have significantly increased muscle mass and strength. [ghr.nlm.nih.gov]
Increased muscle mass in MRMH does not necessarily entail augmented physical strength. Diagnosis is based on clinical findings and supported by genetic tests. Genetic counseling is advisable due to the familial nature of MRMH. [symptoma.com]
Myostatin-related muscle hypertrophy (MRMH) develops because of pathological mutations in the MSTN gene on the long arm of chromosome 2. MRMH has a strong familial component but can also occur sporadically. [symptoma.com]
Differential Diagnosis The MSTN causative variant does not appear to be associated with myopathy or muscle weakness, thus allowing differentiation of myostatin-related muscle hypertrophy from muscular dystrophies with muscle hypertrophy, including: Limb-girdle [ncbi.nlm.nih.gov]
Heterozygotic carriers of MRMH-associated mutations present with a milder MRMH phenotype than homozygotes, suggesting an incomplete autosomal dominant mode of inheritance. [symptoma.com]
They have no plans to take the advice of friends who have jokingly suggested they hire an agent for Liam to line up pro sports deals or modeling contracts. [trulyhuge.com]
We thank Guanwen Shi, Zhaowei Chen, Hualin Zhang, and Zhenhua Lin from Guangzhou General Pharmaceutical Research Institute for suggestions and assistance. [academic.oup.com]
Liam has given his mother a black eye and once punched a hole in the plaster wall during a tantrum. "That's called attitude," his mother said. [trulyhuge.com]
He's a real headache and a half. So - per the child of the original post - I don't feel sorry for the kid. I feel sorry for the kids parents! Talk about a kid who can really give a headache. [theringlord.org]
Clinical Muscle hyperplasia 1st branchial arch: Includes muscles of facial expression & orbicularis oculi 2nd branchial arch: Includes muscles of mastication No evidence of hyperplasia of bone or other organ systems on side of the face Facial nerve: Paresis [neuromuscular.wustl.edu]
Diagnosis of MRMH rests on a thorough analysis of the family history, clinical findings, imaging techniques, and genetic testing for MSTN mutations as well as genetic counseling .
These discussions should explain the hereditary nature of MRMH to the parents of the infant patient and recommend genetic tests not only for their progeny but also for themselves. Parent testing allows a distinction between a hereditary or sporadic occurrence. In case of a parent mutation carrier, further genetic tests of the patient's siblings should be performed .
Clinical findings in MRMH are evident at birth because functional myostatin restrains perinatal skeletal muscle growth. Significant muscle overgrowth on thighs and upper arms, insufficient fat pads, and increased tendon reflexes are hallmark signs in infants  .
Muscle hypertrophy can be visualized with imaging techniques like ultrasonography, magnetic resonance imaging (MRI) or dual energy X-ray absorptiometry (DXA). On the other hand, loss of subcutaneous fat can be revealed with MRI or simply with a caliper  .
Long-term prophylactic monitoring of cardiac function may be advisable .
Genetic testing is required to support the clinical diagnosis. Mutations in the MSTN gene can be shown with polymerase-chain-reaction (PCR) - assisted restriction analysis .
You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments. [rarediseases.info.nih.gov]
Research on adults who share Liam's condition could lead to new treatments for debilitating ailments such as muscular dystrophy and osteoporosis. [trulyhuge.com]
The few treatments being tried to slow its progression have serious side effects. Muscle wasting also is common in the elderly and patients with diseases such as cancer and AIDS. [nbcnews.com]
However you grunt it, the draw to have a treatment that creates muscle – with little exercise needed – is outweighing the medical pursuits of MD cures. [singularityhub.com]
Management Treatment of Manifestations Myostatin-related muscle hypertrophy is not currently known to cause any medical complications. [ncbi.nlm.nih.gov]
Symptoms and Prognosis The major symptoms of myostatin related muscle hypertrophy are reduced subcutaneous fat pad thickness and increased muscle size, according to the US National Library of Medicine. [healthguideinfo.com]
[…] medullary dysplasia; Overgrowth of external genitalia Cardiomyopathy : Occasional Laboratory Hypoglycemia External link: Gene Reviews Myhre Syndrome 8 Mothers against decapentaplegic, drosophila, homolog of, 4 (SMAD4) ; Chromosome 18q21.2; Dominant Epidemiology [neuromuscular.wustl.edu]
Relevant External Links for MSTN Genetic Association Database (GAD) MSTN Human Genome Epidemiology (HuGE) Navigator MSTN Atlas of Genetics and Cytogenetics in Oncology and Haematology: MSTN No data available for Genatlas for MSTN Gene Human adaptive evolution [genecards.org]
But if this gene could be turned off on purpose once a person reached physical maturity then I think it could go a long way to resolving/preventing a lot of the obesity-related medical conditions out there. [theringlord.org]
A genetic mutation prevents some people from producing myostatin. Those individuals can have twice the normal amount of muscle mass, according to medical literature. In Liam's case, the myostatin his body produces is rejected by muscle cells. [trulyhuge.com]
This protein tells your muscles when to stop growing, and in the last few years we’ve seen two babies born with a mutant gene that prevents them from producing enough myostatin. The result? Super Babies. [singularityhub.com]
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