Schuelke et al. (2004) described a child, offspring of a healthy woman who was a former professional athlete, who developed stimulus-induced myoclonus several hours after birth. He appeared extraordinarily muscular, with protruding muscles in his thighs and upper ... Schuelke et al. (2004) described a child, offspring of a healthy woman who was a former professional athlete, who developed stimulus-induced myoclonus several hours after birth. He appeared extraordinarily muscular, with protruding muscles in his thighs and upper arms. Muscle hypertrophy was verified by ultrasonography when the infant was 6 days of age. The stimulus-induced myoclonus gradually subsided after 2 months. The child's motor and mental development were normal. At age 4.5 years, he continued to have increased muscle bulk and strength, and he was able to hold two 3-kg dumbbells in horizontal suspension with his arms extended. Several members in 4 generations of the family were exceptionally strong, according to information in their clinical history.
In a family in which the proband had gross muscle hypertrophy, Schuelke et al. (2004) identified homozygosity for a splice donor site mutation in the MSTN gene (601788.0001). His mother was heterozygous for the mutation, which was not ... In a family in which the proband had gross muscle hypertrophy, Schuelke et al. (2004) identified homozygosity for a splice donor site mutation in the MSTN gene (601788.0001). His mother was heterozygous for the mutation, which was not found in 200 alleles from control subjects. No other family members were available for study.
The diagnosis of myostatin-related muscle hypertrophy is established by clinical findings of reduced subcutaneous fat pad thickness and increased muscle size in individuals with normal or increased muscle strength and an MSTN mutation identified on molecular genetic testing....
DiagnosisClinical DiagnosisThe diagnosis of myostatin-related muscle hypertrophy is established by clinical findings of reduced subcutaneous fat pad thickness and increased muscle size in individuals with normal or increased muscle strength and an MSTN mutation identified on molecular genetic testing.TestingSkeletal muscle size can be measured by ultrasound, DEXA, or MRI. It is expected to be several deviations above normal for age- and sex-matched controls. Subcutaneous fat pad thickness can be measured by ultrasound or with a caliper at various standard locations for which normal values exist.Creatine kinase (CK) serum concentration is expected to be normal. Molecular Genetic TestingGene. MSTN, which encodes the protein growth differentiation factor 8 (also known as myostatin) is the only gene known to be associated with myostatin-related muscle hypertrophy. Table 1. Summary of Molecular Genetic Testing Used in Myostatin-Related Muscle HypertrophyView in own windowGeneTest MethodMutations DetectedMutation Detection Frequency by Test Method 1 Test AvailabilityMSTNDirect DNA 2c.506+5G>AUnknown Research only1. The ability of the test method used to detect a mutation that is present in the indicated gene2. Direct DNA methods may include mutation analysis, mutation scanning, sequence analysis, or other means of molecular genetic testing to detect a genetic alteration associated with myostatin-related muscle hypertrophy.Genetically Related (Allelic) DisordersNo other phenotypes are associated with mutation in MSTN.
Clinical manifestations of myostatin-related muscle hypertrophy appear to be dependent on the amount of myostatin protein present. Therefore both heterozygotes and homozygotes can exhibit muscle hypertrophy. ...
Natural HistoryClinical manifestations of myostatin-related muscle hypertrophy appear to be dependent on the amount of myostatin protein present. Therefore both heterozygotes and homozygotes can exhibit muscle hypertrophy. Homozygotes. A homozygous loss-of-function myostatin mutation was identified in a hypermuscular infant with muscle mass approximately twice that of sex- and age-matched controls [Schuelke et al 2004]. At age 4.5 years, he continued to have increased muscle bulk and strength with normal intellect and normal cardiac function by echocardiography and electrocardiography. He initially displayed stimulus-induced myoclonus that subsided after two months. The relationship between myoclonus and the MSTN mutation is not clear. Ultrasonography revealed normal muscle echogenicity and cross-sectional diameter of quadriceps muscle 7.2 SD above the mean. Heterozygotes. Heterozygotes may have increased muscle bulk and strength. The mother of the child identified to be homozygous for this mutation was a former professional athlete with large calf muscles [Schuelke et al 2004].
This MSTN mutation 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:...
Differential DiagnosisThis MSTN mutation 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:Duchenne and Becker muscular dystrophy (see Dystrophinopathies) Limb-girdle muscular dystrophy 1C (caveolinopathy) (see also Limb-Girdle Muscular Dystrophy Overview) Limb-girdle muscular dystrophies 2C, 2D, 2E (sarcoglycanopthies) (see Limb-Girdle Muscular Dystrophy Overview) Channelopathies such as myotonia congenita, a chloride channelopathy resulting from mutations in CLCN1 The MSTN mutation also causes decreased adipose tissue and needs to be distinguished from familial partial lipodystrophy, Dunnigan type (FPLD2), caused by mutations in LMNA, in which increased muscle mass is not seen [Schmidt et al 2001].Note to clinicians: For a patient-specific ‘simultaneous consult’ related to this disorder, go to , an interactive diagnostic decision support software tool that provides differential diagnoses based on patient findings (registration or institutional access required).
Myostatin-related muscle hypertrophy is not currently known to cause any medical complications. ...
ManagementTreatment of ManifestationsMyostatin-related muscle hypertrophy is not currently known to cause any medical complications. Evaluation of Relatives at RiskSee Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. Therapies Under InvestigationSearch ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this condition.
Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....
Molecular GeneticsInformation in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.Table A. Myostatin-Related Muscle Hypertrophy: Genes and DatabasesView in own windowGene SymbolChromosomal LocusProtein NameHGMDMSTN2q32.2Growth/differentiation factor 8MSTNData are compiled from the following standard references: gene symbol from HGNC; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.Table B. OMIM Entries for Myostatin-Related Muscle Hypertrophy (View All in OMIM) View in own window 601788MYOSTATIN; MSTNNormal allelic variants. Five missense substitutions in conserved amino acid residues have been identified [Ferrell et al 1999]. Two of these, p.Ala55Thr in exon 1 and p.Lys153Arg in exon 2, are polymorphic normal variants in the general population (see Table 2). Pathologic allelic variants. Only one MSTN mutation related to muscle hypertrophy has been reported to date; c.506+5G>A results in a misspliced mRNA (see Table 2; for more information, see Table A).Table 2. Selected MSTN Allelic Variants View in own windowClass of Variant AlleleDNA Nucleotide Change (Alias 1)Protein Amino Acid ChangeReference SequencesNormalc.163G>Ap.Ala55ThrNM_005259.2 NP_005250.1c.458A>Gp.Lys153ArgPathologicc.506+5G>A (IVS1+5G>A)--See Quick Reference for an explanation of nomenclature. GeneReviews follows the standard naming conventions of the Human Genome Variation Society (www.hgvs.org).1. Variant designation that does not conform to current naming conventionsNormal gene product. Myostatin, composed of 375 amino acids, is also known as growth differentiation factor 8 and belongs to the transforming growth factor β superfamily. Myostatin is a negative regulator of muscle growth expressed almost exclusively in developing and adult skeletal muscle [McPherron et al 1997]. Abnormal gene product. The only known mutation results in no detectable myostatin production. Loss or inhibition of myostatin is associated with increased skeletal muscle growth by muscle fiber hyperplasia and hypertrophy [McPherron et al 1997]. Mice heterozygous for an Mstn mutation have muscle mass intermediate between homozygous myostatin null mice and wildtype mice. "Double-muscled" cattle previously linked to the muscular hypertrophy (mh) locus on chromosome 2 have also been found to have mutations in the gene for myostatin [Grobet et al 1997, Kambadur et al 1997].