Zystennieren: Genetische Testung und richtige Einordnung klinisch-therapeutisch zunehmend bedeutsam

Was ist neu?

Autosomal-dominante polyzystische Nieren-Erkrankungen Zystische Nierenerkrankungen sind klinisch und genetisch zunehmend heterogen, auch für die häufigste Form ADPKD wurden kürzlich neue Gene identifiziert. Das Verständnis zu Genotyp-Phänotyp Korrelationen hat sich dabei in den letzten Jahren deutlich verbessert und es macht einen Unterschied für Patient und Familie welcher genaue Genotyp vorliegt. In jedem 4. Fall geht die klassische ADPKD ohne positive Familienanamnese einher (meist aufgrund von Neumutationen). Bei diesen sporadisch imponierenden Fällen und bei Mutationen in autosomal rezessiven Genen kann die restliche Familie in der Regel entlastet werden.

Differenzialdiagnose mit ADPKD-ähnlichen Phänotypen Differenzialdiagnosen mit Mutationen in anderen Genen können zudem klinisch wie ADPKD oder ADPKD-ähnlich imponieren. Dies gilt auch für Tumorsyndrome wie die von Hippel-Lindau Erkrankung, tuberöse Sklerose oder das Birt-Hogg-Dubé Syndrom sowie die rezessiven Zystennieren (ARPKD) und andere Ziliopathien, die ebenfalls wie isolierte Zystennieren erscheinen können. Eine Differenzierung ist aufgrund der unterschiedlichen klinischen Verläufe und anderer Therapieoptionen sehr wichtig.

Welchen Unterschied für die Klinik macht eine genetisch gesicherte Diagnose? Die genaue genetische Einordnung hat große Bedeutung für Patient und Familie. Eine gezielte genetische Beratung mit Angabe von Risiken ist nur mit Kenntnis des Genotyps möglich. Assoziierte Komorbiditäten und organübergreifende Komplikationen können zudem frühzeitig detektiert und gezieltes Screening und Monitoring ermöglicht werden. Dank deutlich verbesserter technischer Möglichkeiten kommt der genetischen Diagnostik im Rahmen der Risikostratifizierung und medikamentös-therapeutischer Optionen ein zunehmend hoher Stellenwert zu. Ein maßgeschneiderter NGS-basierter Ansatz mittels Multi-Gen Panel ist kosteneffizient und in Anbetracht der Vielzahl und Komplexität in Betracht zu ziehender Gene die Methode der Wahl. Hiermit lässt sich die Ätiologie meist klären.

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.

Schlüsselwörter

Zystennieren (ADPKD) - Neumutation - Genotyp-Phänotyp-Korrelation - maßgeschneidertes NGS-Multi-Gen Panel - Risikostratifizierung

Key words

cystic kidneys - autosomal dominant polycystic kidney disease (ADPKD) - genotype-phenotype correlation - customized NGS (Next Generation Sequencing) - genetic diagnostics - risk stratification

Publication History

Article published online:
30 May 2022

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