# Atypical presentations of fetal polycystic kidney disease demonstrates the utility of a genomic autopsy for accurate post-mortem diagnoses

## TL;DR

Genomic autopsy helps diagnose the cause of fetal polycystic kidney disease when traditional methods are unclear, aiding family planning and genetic counseling.

## Contribution

This study demonstrates the effectiveness of genomic autopsy in diagnosing atypical cases of prenatal polycystic kidney disease.

## Key findings

- Genomic autopsy successfully identified the genetic cause of prenatal PKD in all five cases.
- The approach is particularly useful in atypical or inconclusive cases where traditional methods fail.
- A genetic diagnosis helps with future family planning and identifying presymptomatic parents.

## Abstract

Prenatal presentation of polycystic kidney disease (PKD), characterized by bilateral renal cysts and enlarged echogenic kidneys on ultrasound, often results in perinatal death. Prenatal manifestations of PKD are generally associated with autosomal recessive PKD, most commonly a result of pathogenic variants in PKHD1, but in rare cases can also be driven by bi-allelic inheritance of pathogenic variants in genes more commonly associated with autosomal dominant PKD such as PKD1. Diagnosing the underlying cause of prenatal PKD can be complicated by atypical histology, and/or a prenatal phenotype that does not align with family history. In this study, five cases of prenatal PKD with atypical or inconclusive features identified during post-mortem investigations underwent trio exome or genome sequencing, termed a genomic autopsy.

Genomic autopsy was able to delineate the genetic basis of prenatal PKD in all five families.

Our findings demonstrate the diagnostic utility of a genomic autopsy in providing a genetic diagnosis for fetal PKD cases post-mortem, particularly in atypical presentations. A genetic diagnosis is highly beneficial for future family planning, including the use of reproductive technologies, as well as identifying presymptomatic parents who are likely to develop PKD in the future.

The online version contains supplementary material available at 10.1186/s40246-025-00844-4.