Detailed clinical manifestations at onset and prognosis of neonatal-onset Denys-Drash syndrome and congenital nephrotic syndrome of the Finnish type

Clin Exp Nephrol. 2019 Aug;23(8):1058-1065. doi: 10.1007/s10157-019-01732-7. Epub 2019 Apr 8.

Abstract

Background: Neonatal-onset Denys-Drash syndrome (NODDS) is a distinctive clinical entity and has a poor renal and life outcome. Early diagnosis of NODDS is important for managing disorders of sexual development and determining assigned gender. Although patients with NODDS and congenital nephrotic syndrome of the Finnish type (CNF) present with nephrotic syndrome in neonatal life or infancy, the clinical course of NODDS and factors distinguishing these diseases at onset is unknown.

Methods: We performed a retrospective cohort study of patients with NODDS and CNF between 1997 and 2017. Patients with nephrotic syndrome and WT1 or NPHS1 mutations with neonatal onset (within 30 days) were eligible.

Results: We studied eight patients with NODDS and 15 with CNF. The median serum creatinine level at onset in the NODDS group was significantly higher (1.85 mg/dL) than that in the CNF group (0.15 mg/dL; P = 0.002). The median placental/fetal weight ratio in the NODDS and CNF group was 41.8% and 21.0%, respectively (P = 0.001). Kaplan-Meier analysis showed that the median number of days for progression to ESRD from onset in the NODDS and CNF groups was 6 and 910 days, respectively (P < 0.001). All patients in the NODDS group were alive at follow-up. Only one patient in the CNF group died of cardiac complications during follow-up.

Conclusion: CNS, renal dysfunction at onset, and a relatively large placenta are prominent signs of NODDS. Prognosis for patients with NODDS is satisfactory if appropriate and active management is performed.

Keywords: Congenital nephrotic syndrome; Congenital nephrotic syndrome of the Finnish type; Disorders of sexual development; NPHS1; Neonatal dialysis; WT1.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Age of Onset
  • Child
  • Child, Preschool
  • Denys-Drash Syndrome / complications*
  • Denys-Drash Syndrome / diagnosis
  • Denys-Drash Syndrome / genetics
  • Denys-Drash Syndrome / therapy
  • Disease Progression
  • Genetic Predisposition to Disease
  • Humans
  • Infant
  • Infant, Newborn
  • Kidney Failure, Chronic / diagnosis
  • Kidney Failure, Chronic / etiology*
  • Kidney Failure, Chronic / therapy
  • Membrane Proteins / genetics
  • Mutation
  • Nephrotic Syndrome / complications*
  • Nephrotic Syndrome / diagnosis
  • Nephrotic Syndrome / genetics
  • Nephrotic Syndrome / therapy
  • Phenotype
  • Renal Dialysis
  • Retrospective Studies
  • Risk Factors
  • Tokyo
  • WT1 Proteins / genetics

Substances

  • Membrane Proteins
  • WT1 Proteins
  • WT1 protein, human
  • nephrin

Supplementary concepts

  • Nephrosis, congenital