Genetic services in a resource-constrained African setting – diagnostic odysseys, limited testing strategies and the need for exome sequencing

Abstract Background: Exome sequencing is recommended as a first-line investigation for the diagnosis of developmental disorders (DD). It is uncertain if this recommendation can be translated to a low-resource setting, due to a dearth of research into current diagnostic practices in such settings. Results: A file audit performed on 934 patients presenting to a medical genetics clinic in South Africa showed that 83% of patients presented with DD. Patients could be divided into three groups, representing distinct diagnostic pathways. Patient Group A (18%; mean test cost $131) had genetically confirmed aneuploidies. Patient Group B (25%; mean test cost $140) presented with clinically recognizable conditions however only 39% received a genetic diagnostic confirmation. Patient Group C – the largest group (57%; mean test cost $337) – presented with rare, less recognizable conditions and 92% remained undiagnosed after available testing was performed. Conclusions : Patients with DD are the largest group of patients seen in medical genetics clinics in South Africa. Diagnostic testing approaches are limited, so where clinical features are not distinct, the diagnostic yield is low. A significant proportion of these patients would benefit from first-line exome sequencing, from a time, diagnosis and cost perspective, reducing their individual diagnostic odysseys.