Introduction The congenital myopathies are a clinically, genetically and pathologically heterogeneous group of muscle disorders defined in many patients by the presence of particular histopathological features. They emerged as a group of disorders with the wider application of histochemistry and electron microscopy in the 1950s and 1960s, when abnormal structural defects were identified in association with a particular phenotype, before any molecular causes were known. Historically,…

Facioscapulohumeral muscular dystrophy, myotonic muscular dystrophy and oculopharyngeal muscular dystrophy are dominantly inherited disorders, all of which have an unusual molecular defect involving nucleotide repeats. Clinically, facial weakness is a prominent characteristic of all of them. Facioscapulohumeral Muscular Dystrophy Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies, with an estimated prevalence of 1: 8300 to 1:15,000 and a high frequency of sporadic…

Joint contractures are a common complication of several neuromuscular disorders, but in some they are an early feature and specific joints are commonly affected. In particular, disorders known as Emery–Dreifuss muscular dystrophies are characterized by elbow contractures and often associated with a rigid spine and cardiac defects. In this chapter we focus on the Emery–Dreifuss syndromes, in particular those related to defects associated with proteins of…

History and Background The term ‘congenital muscular dystrophy’ (CMD) has been widely used to describe a group of infants with weakness and hypotonia from birth or within the first few months of life. Severe, early contractures are common, and most cases have delayed motor milestones. Detailed clinical studies combined with pathological and molecular studies have revolutionized this field and led to the characterization of several conditions…

History and Background Heterogeneity in the muscular dystrophies has long been recognized ( ). The wide application of molecular techniques and increasing use of next-generation sequencing have identified a growing number of clinical entities, and their gene and protein defects, described as ‘limb-girdle muscular dystrophies’ (LGMD). This is a diverse group of disorders with either autosomal dominant or autosomal recessive inheritance ( Tables 11.1 and 11.2…

Background Although the advent of molecular genetics has transformed the diagnostic confirmation of Duchenne and Becker muscular dystrophy, we thought it worth retaining some historical background and clinical description of these classical muscular disorders. Duchenne muscular dystrophy (DMD) has been recognized as a clinical entity since the 19th century. In 1868, Duchenne gave a detailed account of 13 male patients with progressive muscle weakness ( ).…

There are many inherited and acquired clinical disorders caused by a defect in upper or lower motor neurone or the peripheral nerve. These include amyotrophic lateral sclerosis (ALS; upper and lower motor neurone), hereditary motor and sensory neuropathies (HMSNs; motor and sensory neurone and peripheral nerves), the spinal muscular atrophies (SMAs; lower motor neurone) and inflammatory peripheral neuropathies. In addition, ageing of muscle, some metabolic conditions,…

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When the pathologist is asked to evaluate a muscle biopsy, much of the interpretation is based on his or her previous experience and the recognition of similarities between the biopsy and muscle from known diseases. In some instances, such as an advanced dystrophy or a spinal muscular atrophy, the changes may be striking and unequivocal. In others, the changes may be more subtle and a systematic…

Immunohistochemistry Immunohistochemistry has an essential role in the evaluation of muscle biopsies and in examining protein localization. The term ‘protein expression’ is often applied to describe immunohistochemical results, but it should be remembered that the technique only reflects localization of a protein, not the related RNA synthesis, and the gene coding for it may not be active at the time the protein is localized. In addition,…

Skeletal muscle undergoes many changes in response to disease and trauma. With the electron microscope, the abnormalities seen at the light level can be characterized and accurately localized, and the variety of changes affecting each organelle identified. The interpretation of the pathological abnormalities observed in a muscle biopsy must take into account several factors, in particular the small sample size, possible artefacts induced by preparation and…

This chapter deals with the various changes that may occur in a muscle under pathological conditions. As we show, very few abnormalities are in themselves pathognomonic of a particular disease. However, by evaluating the constellation of different changes that are present within a given biopsy, and assessing these in the context of clinical features of the patient, one can often obtain a fairly accurate diagnosis. To…

In this chapter, the composition and appearance of normal muscle will be discussed. The first part will be concerned with the anatomical constituents of normal muscle at the light microscope level, followed by histochemical aspects of the different types of muscle fibres and ultrastructural details of muscle. We then discuss myogenesis and the development of muscle. Histological Structure The word muscle is derived from the Latin…

Just as every pathologist has particular preferences for routine stains, so muscle histochemists have tended to develop preferences for particular reactions, especially in the interpretation of fibre types. In the early days of the application of histochemical techniques to the study of muscle, large batteries of enzymes were routinely studied in muscle biopsies (see ). While these many enzyme reactions were of special interest and value…

The Evolving Role of Muscle Pathology Muscle biopsy has been an important part of the assessment of patients with a neuromuscular disorder for many decades. The use of frozen sections and the application of histochemistry and electron microscopy have identified many pathological features that have defined and diagnosed a disorder. The molecular genetic revolution that began with the discovery of the gene responsible for Duchenne muscular…