Pegoraro Elena, Hoffman Eric P
Department of Neurosciences, University of Padova, Padova, Italy
Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC
NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.
Limb-girdle muscular dystrophy (LGMD) is a purely descriptive term, generally reserved for childhood- or adult-onset muscular dystrophies that are distinct from the much more common X-linked dystrophinopathies. LGMDs are typically nonsyndromic, with clinical involvement typically limited to skeletal muscle. Individuals with LGMD generally show weakness and wasting restricted to the limb musculature, proximal greater than distal, and muscle degeneration/regeneration on muscle biopsy. Most individuals with LGMD show relative sparing of the bulbar muscles, although exceptions occur, depending on the genetic subtype. Onset, progression, and distribution of the weakness and wasting vary considerably among individuals and genetic subtypes.
DIAGNOSIS/TESTING: The limb-girdle muscular dystrophies typically show degeneration/regeneration (dystrophic changes) on muscle biopsy, which is usually associated with elevated serum creatine kinase concentration. For any male or female suspected of having limb-girdle muscular dystrophy, it is necessary to first rule out an X-linked dystrophinopathy. Biochemical testing (i.e., protein testing by immunostaining or immunblotting) performed on a muscle biopsy can establish the diagnosis of the following LGMD types: sarcoglycanopathy, calpainopathy, dysferlinopathy, and O-linked glycosylation defects (also known as dystroglycanopathy). In some cases, demonstration of complete or partial deficiencies for any particular protein can then be followed by mutation studies of the corresponding gene. Pathogenic variants in a number of genes have been associated with types of LGMD.
The term LGMD1 (including, e.g., LGMD1A, LGMD1B) refers to genetic types showing dominant inheritance, whereas LGMD2 refers to types with autosomal recessive inheritance. Pathogenic variants at more than 50 loci have been reported, making accurate diagnosis and genetic counseling a challenge. In most instances, the proband represents a simplex case, and the families can be counseled for recurrence risks associated with rare autosomal recessive conditions, which leaves a "significant" risk only for the sibs of the proband. If the causative pathogenic variant(s) have been identified in the family, prenatal testing for pregnancies at increased risk is possible.
No definitive treatments for the limb-girdle muscular dystrophies exist. Management should be tailored as much as possible to each individual and each specific LGMD type. Management to prolong survival and improve quality of life includes weight control to avoid obesity, physical therapy and stretching exercises to promote mobility and prevent contractures, use of mechanical aids to help ambulation and mobility, surgical intervention for orthopedic complications, use of respiratory aids when indicated, monitoring for cardiomyopathy in LGMD types with cardiac involvement, and social and emotional support and stimulation.
注意：本出版物已停用。此存档版本仅用于历史参考，信息可能已过时。
肢带型肌营养不良症（LGMD）是一个纯粹的描述性术语，通常用于指儿童期或成人期发病的肌营养不良症，与更为常见的X连锁肌营养不良症不同。LGMD通常无综合征表现，临床受累通常仅限于骨骼肌。LGMD患者一般表现为肢体肌肉组织无力和萎缩，近端重于远端，肌肉活检显示肌肉变性/再生。大多数LGMD患者的延髓肌相对不受累，不过也有例外，具体取决于基因亚型。个体和基因亚型之间，无力和萎缩的起病、进展及分布差异很大。
诊断/检测：肢带型肌营养不良症在肌肉活检时通常显示变性/再生（营养不良性改变），这通常与血清肌酸激酶浓度升高有关。对于任何疑似患有肢带型肌营养不良症的男性或女性，首先必须排除X连锁肌营养不良症。对肌肉活检进行生化检测（即通过免疫染色或免疫印迹进行蛋白质检测）可确诊以下LGMD类型：肌聚糖病、钙蛋白酶病、dysferlin病和O-连接糖基化缺陷（也称为肌营养不良聚糖病）。在某些情况下，确定任何特定蛋白质完全或部分缺乏后，可对相应基因进行突变研究。许多基因中的致病变异与LGMD类型有关。
术语LGMD1（包括例如LGMD1A、LGMD1B）指显示显性遗传的基因类型，而LGMD2指常染色体隐性遗传的类型。已报道50多个位点的致病变异，这使得准确诊断和遗传咨询成为一项挑战。在大多数情况下，先证者代表单纯病例，可就与罕见常染色体隐性疾病相关的复发风险为家庭提供咨询，这仅给先证者的同胞留下“显著”风险。如果已在家族中确定致病的致病变异，则可对风险增加的妊娠进行产前检测。
目前不存在针对肢带型肌营养不良症的确切治疗方法。管理应尽可能根据每个个体和每种特定的LGMD类型进行调整。延长生存期和改善生活质量的管理措施包括控制体重以避免肥胖、进行物理治疗和伸展运动以促进活动能力并预防挛缩、使用辅助器械帮助行走和活动、对骨科并发症进行手术干预、在有指征时使用呼吸辅助设备、对有心脏受累的LGMD类型监测心肌病，以及提供社会和情感支持与激励。
