Approach to the diagnosis of congenital myopathies

TLDR

Recent advances have clarified the genetic basis of many congenital myopathies, yet the link between histological subtypes and specific genes remains complex, with multiple genes implicated in a single pathology and the same gene causing diverse muscle disorders. The committee aimed to create a consensus guideline summarizing clinical, pathological, and imaging features that distinguish congenital myopathy subtypes and guide targeted genetic testing. The guideline was developed through a literature review, expert consultation, two rounds of online surveys, and a three‑day workshop to refine the consensus statement. The resulting consensus statement offers clinicians practical guidelines for evaluating hypotonic children, prioritizing genetic testing, and interpreting next‑generation sequencing results to identify pathogenic variants.

Abstract

Over the past decade there have been major advances in defining the genetic basis of the majority of congenital myopathy subtypes. However the relationship between each congenital myopathy, defined on histological grounds, and the genetic cause is complex. Many of the congenital myopathies are due to mutations in more than one gene, and mutations in the same gene can cause different muscle pathologies. The International Standard of Care Committee for Congenital Myopathies performed a literature review and consulted a group of experts in the field to develop a summary of (1) the key features common to all forms of congenital myopathy and (2) the specific features that help to discriminate between the different genetic subtypes. The consensus statement was refined by two rounds of on-line survey, and a three-day workshop. This consensus statement provides guidelines to the physician assessing the infant or child with hypotonia and weakness. We summarise the clinical features that are most suggestive of a congenital myopathy, the major differential diagnoses and the features on clinical examination, investigations, muscle pathology and muscle imaging that are suggestive of a specific genetic diagnosis to assist in prioritisation of genetic testing of known genes. As next generation sequencing becomes increasingly used as a diagnostic tool in clinical practise, these guidelines will assist in determining which sequence variations are likely to be pathogenic.