Myopathology of Inherited Myopathies

Inherited myopathies are a large group of neuromuscular disorders presenting with muscular weakness associated with variable respiratory and cardiac involvement. They include early onset entities as well as myopathies revealing at adult age. They belong to different nosologic groups created on different bases such as the distribution of muscular weakness (e.g. limb girdle muscular dystrophy), the enzyme or defective protein (e.g. muscle glycogenoses), or the histopathologic lesion found in muscle biopsy (e.g. congenital structural myopathies, myofibrillar myopathies). Given the expanding number of genes involved, genetic diagnosis through next generation sequencing approaches (such as exome sequencing or genome sequencing) is the most effective diagnostic tool. However, these techniques are not available everywhere, they preferentially require sampling of parents and other relatives, and they represent a burdensome and long lasting bioinformatic analysis that hinders or delays the setting up of a clear diagnosis. Moreover, they often identify multiple genetic variants in different genes that need a functional validation of pathogenicity. In this scenario, muscle biopsy renews its importance as being able to provide diagnostic indications in a short amount of time, and allowing the performance of different techniques spanning from histochemistry, electron microscopy, and biochemical studies. When used in conjunction, these studies provide a complete view of the muscle damage and can be also useful in the interpretation of uncertain genetic variants.

An analysis of the recent literature published on inherited neuromuscular disorders tends to propose the next generation genetic approaches as the ‘panacea’ for the diagnostic difficulties encountered by myologists in their routine. In parallel, we assist to a stigmatization of the muscle biopsy procedure that is invasive, and only allow the analyses of a small fragment of a specific muscle, that cannot be considered specific of a global pathologic process. These new tendencies contrast with the reality where a multidisciplinary and complementary approach, including all different examinations, is often needed to give a definite diagnosis to patients. In many settings, the clinician externalizes the exome sequencing analysis, and then receives a list of variants. In both situations, there is a need to go back to the clinics and muscle tissue to pick the right gene. With our Research Topic, we aim to evaluate the actual yield of muscle biopsy analyses in different groups of inherited myopathies. The goal is to reaffirm the role of the muscle biopsy in specific conditions and to build interest in investing human and material resources to promoting the field of myopathology. We estimate that this topic will help greatly in determining when a muscle biopsy is still needed in the diagnostic follow up on inherited myopathies.

For this Topic we would like to attract experts in the field of inherited myopathies to contribute with their reporting of myopathologic features of already described conditions, or to describe the myopathologic aspects of novel myopathies. These contributions should help in creating a clear vision of the scenarios where histopathologic analyses can help in the diagnosis of inherited myopathies, and what analyses are needed according to the distinct pathologies. Furthermore, we would welcome papers assessing the role of muscle biopsy in the translational research of inherited myopathies, such as the identification of specific myopathologic outcome measures for novel therapeutic approaches like gene therapy or genome editing approaches. For this Topic we welcome submissions of:

• Original Research
• Brief Research Reports
• Reviews of specific myopathology topics

Topic Editor Edoardo Malfatti has an ongoing contract with Spark for providing services in muscle biopsy analyses. the other Topic Editors declare no competing interests with regards to the Research Topic subject.