Myostatin-related muscle hypertrophy (MRMH) develops because of pathological mutations in the MSTN gene on the long arm of chromosome 2 [1] [2]. MRMH has a strong familial component but can also occur sporadically [3]. Heterozygotic carriers of MRMH-associated mutations present with a milder MRMH phenotype than homozygotes, suggesting an incomplete autosomal dominant mode of inheritance [4].

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 [5] [6]. Skeletal muscle overgrowth in MRMH can lead to an effective doubling of muscle tissue volume with a concomitant loss of subcutaneous fat [7] [8]. Additionally, infant MRMH patients can also show increased tendon reflexes and congenital stimulus-induced myoclonus, which should resolve spontaneously after a few months [1].

The effect MRMH-associated muscle growth is still under dispute. While MRMH cases in humans seem to suggest increased physical strength in children [1], 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 [9].

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 [9].

• Lactose Intolerance

  He also had eczema, enlarged kidneys, was lactose intolerant and had severe stomach reflux that made him vomit several times each day, his mother said. [ctvnews.ca]

• Regurgitation

  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]

  Myostatin-related muscle hypertrophy (or myotonic hypertrophy) is a rare genetic condition characterized by reduced body fat and increased skeletal muscle size. Affected individuals have up to twice the usual amount of muscle mass in their bodies. [en.wikipedia.org]

  Myostatin-related muscle hypertrophy is a rare condition characterized by reduced body fat and increased muscle size. Affected individuals have up to twice the usual amount of muscle mass in their bodies. [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]

• Osteoporosis

  Scientists hope to further study of the phenomenon to develop treatments for conditions such as brittle-bone disease and osteoporosis. [statnews.com]

  Scientists hope to further study of the phenomenon to develop treatments for conditions such as brittle-bone disease and osteoporosis. This story was produced by STAT, a national publication covering health, medicine, and life science. [theweek.com]

  Research on adults who share Liam's condition could lead to new treatments for debilitating ailments, such as muscular dystrophy and osteoporosis. [mlive.com]

  Research on adults who share Liam's condition could lead to new treatments for debilitating ailments such as muscular dystrophy and osteoporosis. [ctvnews.ca]

• Long Arm

  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]

• Muscle Weakness

  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]

• Suggestibility

  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. [ctvnews.ca]

• Tantrums

  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. [ctvnews.ca]

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 [10].

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 [10].

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 [1] [11].

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 [1] [10].

Long-term prophylactic monitoring of cardiac function may be advisable [1].

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 [1].

CLOSE Medical Disclaimer The medical information on this site is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. [diseaseinfosearch.org]

Treatment - Myostatin-related muscle hypertrophy Myostatin-related muscle hypertrophy is not currently known to cause any medical complications. Resources - Myostatin-related muscle hypertrophy Not supplied. [checkorphan.org]

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]

Ironically, learning more about it could lead to treatments for other muscle afflictions, researchers say. [cbsnews.com]

Prognosis - Myostatin-related muscle hypertrophy Not supplied. Treatment - Myostatin-related muscle hypertrophy Myostatin-related muscle hypertrophy is not currently known to cause any medical complications. [checkorphan.org]

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]

Prevention - Myostatin-related muscle hypertrophy Not supplied. Diagnosis - Myostatin-related muscle hypertrophy Skeletal muscle size in an individual with myostatin-related muscle hypertrophy is measured by ultrasound examination, DEXA, or MRI. [checkorphan.org]

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]

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. [ctvnews.ca]

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2. McPherron AC, Lee SJ. Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci USA. 1997;94(23):12457-12461.
3. Szabo G, Dallmann G, Muller G, Patthy L, Soller M, Varga L. A deletion in the myostatin gene causes the compact (Cmpt) hypermuscular mutation in mice. Mamm Genome. 1998;9(8):671-672.
4. Amthor H, Huang R, McKinnell I, et al. The regulation and action of myostatin as a negative regulator of muscle development during avian embryogenesis. Dev Biol. 2002;251(2):241-257.
5. Zimmers TA, Davies MV, Koniaris LG, et al. Induction of cachexia in mice by systemically administered myostatin. Science. 2002;296(5572):1486-1488.
6. Gonzalez-Cadavid NF, Taylor WE, Yarasheski K, et al. Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting. Proc Natl Acad Sci USA. 1998; 95(25): 14938-14943.
7. Grobet L, Martin LJR, Poncelet D, et al. A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nat Genet. 1997;17(1):71-74.
8. Lin J, Arnold HB, Della-Fera MA, Azain MJ, Hartzell DL, Baile CA. Myostatin knockout in mice increases myogenesis and decreases adipogenesis. Biochem Biophys Res Commun. 2002;291(3):701-706
9. Amthor H, Macharia R, Navarrete R, et al. Lack of myostatin results in excessive muscle growth but impaired force generation. Proc Nat Acad Sci USA. 2007;104(6):1835-1840.
10. Wagner KR, Cohen JS. Myostatin-Related Muscle Hypertrophy. 2005. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews®. Seattle, WA: University of Washington, Seattle; 1993-2017. https://www.ncbi.nlm.nih.gov/books/NBK1498/?report=reader. Accessed Nov 7th, 2017.
11. McPherron AC, Lee SJ. Suppression of body fat accumulation in myostatin-deficient mice. J Clin Invest. 2002;109(5):595-601.