Department of Pathology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India.
Department of Pathology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India.
Indian J Pathol Microbiol. 2022 May;65(Supplement):S259-S270. doi: 10.4103/ijpm.ijpm_1074_21.
Muscular dystrophies are a clinically and genetically heterogeneous group of disorders involving the skeletal muscles. They have a progressive clinical course and are characterized by muscle fiber degeneration. Congenital muscular dystrophies (CMD) include dystroglycanopathies, merosin-deficient CMD, collagen VI-deficient CMD, SELENON-related rigid spine muscular dystrophy, and LMNA-related CMD. Childhood and adult-onset muscular dystrophies include dystrophinopathies, limb-girdle muscular dystrophies, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. Traditionally, muscle biopsy and histopathology along with special pathology techniques such as immunohistochemistry or immunoblotting were used for the diagnosis of muscular dystrophies. However, recent advances in molecular genetic testing, especially the next-generation sequencing technology, have revolutionized the diagnosis of muscular dystrophies. Identification of the underlying genetic basis helps in appropriate management and prognostication of the affected individual and genetic counseling of the family. In addition, identification of the exact disease-causing mutations is necessary for accurate prenatal genetic testing and carrier testing, to prevent recurrence in the family. Mutation identification is also essential for initiating mutation-specific therapies (which have been developed recently, especially for Duchenne muscular dystrophy) and for enrolment of patients into ongoing therapeutic clinical trials. The 'genetic testing first' approach has now become the norm in most centers. Nonetheless, muscle biopsy-based testing still has an important role to play, especially for cases where genetic testing is negative or inconclusive for the etiology.
肌肉疾病是一组涉及骨骼肌的具有临床和遗传异质性的疾病。它们具有进行性临床病程，其特征为肌肉纤维变性。先天性肌肉疾病（CMD）包括肌聚糖病、先天性肌无力综合征、胶原 VI 缺乏性 CMD、SEELENON 相关刚性脊柱肌肉疾病和 LMNA 相关 CMD。儿童和成年起病的肌肉疾病包括肌营养不良症、肢带型肌肉疾病、Emery-Dreifuss 肌肉疾病、面肩肱型肌营养不良和强直性肌营养不良。传统上，肌肉活检和组织病理学以及特殊的病理学技术（如免疫组化或免疫印迹）用于肌肉疾病的诊断。然而，分子遗传学检测的最新进展，特别是下一代测序技术，彻底改变了肌肉疾病的诊断。确定潜在的遗传基础有助于对个体进行适当的管理和预后判断，并为家庭提供遗传咨询。此外，确定确切的致病突变对于准确的产前基因检测和携带者检测、预防家庭复发至关重要。突变鉴定对于启动特定突变的治疗（最近已开发出这些治疗方法，尤其是针对杜氏肌营养不良症）以及招募患者参加正在进行的治疗性临床试验也是必要的。“首先进行基因检测”的方法现在已成为大多数中心的常规做法。尽管如此，基于肌肉活检的检测仍然具有重要作用，尤其是对于基因检测结果为阴性或病因不确定的病例。
