Myostatin Mutation Associated with Gross Muscle Hypertrophy in a Child

uscle wasting and weakness are among the most common inherited and acquired disorders and include the muscular dystrophies, cachexia, and age-related wasting.Since there is no generally accepted treatment to improve muscle bulk and strength, these conditions pose a substantial burden to patients as well as to public health.Consequently, there has been considerable interest in a recently described inhibitor of muscle growth, myostatin, or growth/ differentiation factor 8 (GDF-8), which belongs to the transforming growth factor b superfamily of secreted proteins that control the growth and differentiation of tissues throughout the body.The myostatin gene is expressed almost exclusively in cells of skeletal-muscle lineage throughout embryonic development as well as in adult animals and functions as a negative regulator of muscle growth.1,2 Targeted disruption of the myostatin gene in mice doubles skeletal-muscle mass. 1 Conversely, systemic overexpression of the myostatin gene leads to a wasting syndrome characterized by extensive muscle loss.3 In adult animals, myostatin appears to inhibit the activation of satellite cells, which are stem cells resident in skeletal muscle.4,5 The potential relevance of myostatin to the treatment of disease in humans has been suggested by studies involving mdx mice, which carry a mutation in the dystrophin gene and therefore serve as a genetic model of Duchenne's and Becker's muscular dystrophy.6 For example , mdx mice that lacked myostatin were found not only to be stronger and more muscular than their mdx counterparts with normal myostatin, but also to have reduced fibrosis and fatty remodeling, suggesting improved regeneration of muscle.7 Furthermore, injection of neutralizing monoclonal antibodies directed against myostatin into either wild-type or mdx mice increases muscle mass and specific force, suggesting that myostatin plays an important role in regulating muscle growth in adult animals.8,9 The function of myostatin appears to be conserved across species, since mutations in the myostatin gene have been shown to be responsible for the "double-muscling" phenotype in cattle.[10][11][12][13] The phenotypes of mice and cattle lacking myostatin and the high degree of sequence conservation of the predicted myostatin protein in many mammalian species have raised the possibility that myostatin may help regulate muscle growth in humans.We report the identification of a myostatin mutation in a child with muscle hypertrophy, thereby providing strong evidence that myostatin does play an important role in regulating muscle mass in humans.A healthy woman who was a former professional athlete gave birth to a son after a normal pregnancy.The identity of the child's father was not revealed.The child's birth weight was in the 75th percentile.Stimulus-induced myoclonus developed several m case report