Overcoming genetic neuromuscular diagnostic pitfalls in a middle-income country

Abstract

Abstract Neuromuscular disorders affect almost 20 million people worldwide. Advances in molecular diagnosis have provided valuable insights into neuromuscular disorders, allowing for improved standards of care and targeted therapeutic approaches. Despite this progress, access to genomic diagnosis remains scarce and inconsistent in middle-income countries such as Brazil. The lack of public health policies to enable feasible genetic diagnosis and the shortage of neuromuscular disorders specialists are the main reasons in this process. We report our experience in a transcontinental genomic consortium for neuromuscular disorders highlighting how collaborative efforts have helped overcome various obstacles in diagnosing our patients. We describe several challenging cases categorized into three major themes, underlining significant gaps in genetic diagnosis: (i) reverse phenotyping and variant validation, (ii) deep phenotyping and identifying a bespoke molecular approach, and (iii) exploring the use of genomic tests beyond whole exome sequencing. We applied a qualitative case-based approach to exemplify common pitfalls in genomic diagnosis in a middle-income country. Our experience has shown that establishing a virtual transcontinental partnership is viable, offering effective exchange of scientific experiences, providing both guidance for rational decision-making and specialized training on a local level and access to diverse molecular diagnosis strategies and functional analyses. Collaborative efforts such as these have the potential to overcome local obstacles, strengthen scientific capabilities, foster diverse multi-ethnic cohorts, and ultimately provide improved care for patients.