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. 2017 Apr;295(4):897-906. doi: 10.1007/s00404-017-4336-6. Epub 2017 Mar 10.

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.

Keywords: Autosomal recessive polycystic kidney disease; Cystic kidney disease; Fetal ultrasound; Prenatal diagnosis.

MeSH terms

  • Ciliary Motility Disorders / diagnostic imaging
  • Diagnosis, Differential
  • Encephalocele / diagnostic imaging
  • Female
  • Genetic Association Studies*
  • Humans
  • Kaplan-Meier Estimate
  • Kidney / abnormalities
  • Kidney / diagnostic imaging
  • Male
  • Mutation
  • Polycystic Kidney Diseases / diagnostic imaging
  • Polycystic Kidney, Autosomal Recessive / diagnostic imaging*
  • Polycystic Kidney, Autosomal Recessive / embryology
  • Polycystic Kidney, Autosomal Recessive / genetics
  • Prognosis
  • Receptors, Cell Surface / genetics
  • Retinitis Pigmentosa
  • Retrospective Studies
  • Ultrasonography

Substances

  • PKHD1 protein, human
  • Receptors, Cell Surface

Supplementary concepts

  • Meckel syndrome type 1