Wagner Kathryn R, Cohen Julie S
Kennedy Krieger Institute, Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland
Kennedy Krieger Institute, Baltimore, Maryland
NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.
Myostatin-related muscle hypertrophy is characterized by reduced subcutaneous fat pad thickness and increased muscle size in individuals with normal or increased muscle strength. Both heterozygotes and homozygotes for a causative variant in encoding the protein growth differentiation factor 8 (myostatin) can exhibit muscle hypertrophy. Clinical manifestations depend on the amount of myostatin protein present. An infant homozygous for an causative variant had muscle mass twice that of sex- and age-matched controls; intellect and cardiac function were normal. He displayed stimulus-induced myoclonus that subsided after two months. Heterozygotes may have increased muscle bulk and strength, but to a lesser degree.
DIAGNOSIS/TESTING: Skeletal muscle size in an individual with myostatin-related muscle hypertrophy is measured by ultrasound examination, DEXA, or MRI. Subcutaneous fat pad thickness is measured by ultrasound or with a caliper. is the only gene in which mutation is known to cause myostatin-related muscle hypertrophy.
Myostatin-related muscle hypertrophy is not known to cause medical complications.
The phenotypes associated with myostatin-related muscle hypertrophy are inherited in an incomplete autosomal dominant manner. At conception, the sibs of a child with homozygous myostatin-related muscle hypertrophy have a 25% chance of having homozygous myostatin-related muscle hypertrophy, a 50% chance of having one causative variant with or without increased muscle mass, and a 25% chance of having normal muscle mass and no causative variants. Heterozygotes may have increased muscle mass. Individuals diagnosed with heterozygous myostatin-related muscle hypertrophy may have a parent with the causative variant who may have increased muscle mass, or the proband may have the condition as the result of a variant. The proportion of cases caused by a variant is unknown. The chance that sibs of a proband with heterozygous myostatin-related muscle hypertrophy will inherit the variant is 50% if a parent has increased muscle mass or has an causative variant. Each child of an individual with heterozygous myostatin-related muscle hypertrophy has a 50% chance of inheriting the causative variant.
注意：本出版物已停用。此存档版本仅用于历史参考，信息可能过时。
与肌生成抑制素相关的肌肉肥大的特征是，在肌肉力量正常或增强的个体中，皮下脂肪垫厚度减小，肌肉尺寸增大。编码蛋白质生长分化因子8（肌生成抑制素）的致病变体的杂合子和纯合子均可表现出肌肉肥大。临床表现取决于肌生成抑制素蛋白的含量。一名纯合致病变体的婴儿，其肌肉量是性别和年龄匹配的对照组的两倍；智力和心脏功能正常。他表现出刺激诱发的肌阵挛，两个月后消退。杂合子的肌肉量和力量可能增加，但程度较轻。
诊断/检测：通过超声检查、双能X线吸收法（DEXA）或磁共振成像（MRI）测量与肌生成抑制素相关的肌肉肥大个体的骨骼肌大小。通过超声或卡尺测量皮下脂肪垫厚度。[具体基因名称未给出]是已知突变会导致与肌生成抑制素相关的肌肉肥大的唯一基因。
与肌生成抑制素相关的肌肉肥大不会引起医学并发症。
与肌生成抑制素相关的肌肉肥大相关的表型以不完全常染色体显性方式遗传。在受孕时，患有纯合性肌生成抑制素相关肌肉肥大的儿童的同胞有25%的机会患有纯合性肌生成抑制素相关肌肉肥大，有50%的机会携带一个致病变体，无论肌肉量是否增加，有25%的机会肌肉量正常且无致病变体。杂合子的肌肉量可能增加。被诊断为杂合性肌生成抑制素相关肌肉肥大的个体，其父母可能携带致病变体且肌肉量增加，或者先证者可能因新发变体而患病。由新发变体导致的病例比例未知。如果父母的肌肉量增加或携带致病变体，杂合性肌生成抑制素相关肌肉肥大先证者的同胞继承该变体的机会为50%。杂合性肌生成抑制素相关肌肉肥大个体的每个孩子继承致病变体的机会为50%。
