Polycystic kidneys: Genetic testing and correct classification clinically and therapeutically of increasing significance

Abstract

Cystic kidney disease is a clinically and genetically diverse group of diseases, with more than 100 genes known to date. One in 500 is affected worldwide, mostly due to a malfunction of cilia. New genes have been identified recently for the most common form autosomal dominant polycystic kidney disease (ADPKD). Every fourth ADPKD patient is lacking a positive family history (mostly due to a de novo mutation); in these cases remaining family members can be relieved. Differentiation of entities just based on clinical and imaging data is often most challenging. However, an accurate classification is significant for the patient and family. Associated comorbidities and cross-organ complications can be detected early and targeted screening and monitoring can be facilitated. Relatives also benefit from an accurate and early diagnosis. Precise genetic counselling with indication of risks is only possible by knowing the concise disease genotype. Genetic diagnostics is becoming increasingly important in this context and in terms of risk stratification and drug-therapeutic options. The understanding of genotype-phenotype correlations has improved significantly in recent years. Wet and dry lab processes as well as the interpretation of genetic data for ADPKD require a high level of expertise. Differential diagnoses with mutations in other genes underlie patients with "ADPKD" or ADPKD-like phenotypes much more frequently than usually assumed. Due to the number and complexity of genes that need to be considered, a tailored NGS (Next Generation Sequencing) approach using a customized, well-balanced multi-gene panel is cost-effective and currently the method of choice. Differences in the quality of laboratories must be taken into account. With this, the genetic etiology and underlying mutation(s) can be found in most cases.