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Prenatal ultrasound, genotype, and outcome in a large cohort of prenatally affected patients with autosomal-recessive polycystic kidney disease and other hereditary cystic kidney diseases

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

To investigate the sonographic and clinical genotype–phenotype correlations in autosomal recessive polycystic kidney disease (ARPKD) and other cystic kidney diseases (CKD) in a large cohort of prenatally detected fetuses with hereditary CKD.

Methods

We retrospectively studied the clinical and diagnostic data of 398 patients referred with prenatal ultrasound findings suggestive of CKD between 1994 and 2010. Cases with confirmed hereditary CKD (n = 130) were analyzed as to their prenatal ultrasound findings, genotype, and possible predictors of clinical outcome.

Results

ARPKD was most common in our non-representative sample. Truncating PKHD1 mutations led to a significantly reduced neonatal prognosis, with two such mutations being invariably lethal. Sonographically visible kidney cysts occurred in only 3% of ARPKD cases. Renal abnormalities in Meckel syndrome (MKS) appeared earlier than in ADPKD (19.6 ± 3.7 vs. 29.8 ± 5.1 GW) or ARPKD (19.6 ± 3.7 vs. 30.2 ± 1.2 GW). Additional CNS malformations were not found in ARPKD, but were highly sensitive for MKS. Pulmonary hypoplasia, oligo/anhydramnios (OAH), and kidney enlargement were associated with a significantly worse neonatal prognosis.

Conclusion

Genotype, sonographic signs of OAH, enlarged kidney size, and pulmonary hypoplasia can be useful predictors of neonatal survival. We propose sonographic morphological criteria for ARPKD, ADPKD, MKS, and renal cyst and diabetes syndrome (RCAD). We further propose a clinical diagnostic algorithm for differentiating cystic kidney diseases.

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Author contribution

FE: Data collection and analysis, manuscript writing. NOB: Support with data collection, manuscript editing. UG: Manuscript editing, acquisition and analysis of the fetal ultrasound pictures included in the manuscript. KZ: Study/protocol planning and oversight, manuscript editing.

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Authors and Affiliations

  1. Institute of Human Genetics, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany

    Florian Erger, Nadina Ortiz Brüchle & Klaus Zerres

  2. Institute of Human Genetics, Cologne University Hospital, Cologne, Germany

    Florian Erger

  3. Department of Obstetrics and Prenatal Medicine, Bonn University Hospital, Bonn, Germany

    Ulrich Gembruch

Authors
  1. Florian Erger
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  2. Nadina Ortiz Brüchle
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  3. Ulrich Gembruch
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  4. Klaus Zerres
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Correspondence to Klaus Zerres.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study of existing clinical data is purely retrospective and non-interventional. Data were archived with the patient’s or their legal guardian’s informed consent. This study falls under previous local IRB approval of genotype/phenotype studies in cystic kidney disease (decision of the Ethics Committee of the University Hospital Aachen). The study is in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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For this type of study, formal consent is not required.

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Erger, F., Brüchle, N.O., Gembruch, U. et al. Prenatal ultrasound, genotype, and outcome in a large cohort of prenatally affected patients with autosomal-recessive polycystic kidney disease and other hereditary cystic kidney diseases. Arch Gynecol Obstet 295, 897–906 (2017). https://doi.org/10.1007/s00404-017-4336-6

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  • DOI: https://doi.org/10.1007/s00404-017-4336-6

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