Renal Tubular Dysgenesis: Broadening the Discussion of the Etiological Spectrum

TL;DR

This case report describes a rare kidney disorder in a newborn with an unusual genetic cause, highlighting the complexity of its underlying mechanisms.

Contribution

The report presents a novel case of renal tubular dysgenesis with a de novo chromosomal duplication unrelated to RAS genes.

Findings

The patient had a chromosomal duplication dup(1)(q24.1q25.1) not involving RAS genes.

The case lacked classic cardiovascular dysfunction and had an atypical presentation of renal tubular dysgenesis.

The findings suggest alternative pathophysiological mechanisms may contribute to RTD.

Abstract

Renal tubular dysgenesis (RTD) is a rare disorder characterized by impaired development of the renal tubules. It is often a fatal condition that should be considered in the differential diagnosis of neonatal kidney failure. RTD can be classified as primary (linked to deleterious variants in genes encoding renin-angiotensin system (RAS) proteins) or secondary to an underlying cause. In this case report, we present a late preterm female neonate born at 35 weeks by elective cesarean section due to oligohydramnios and fetal growth restriction. At birth, she exhibited hypotonia and features consistent with Potter sequence and developed persistent anuric kidney failure, fluid-responsive hypotension, and respiratory distress requiring non-invasive ventilation. Kidney ultrasound revealed no significant abnormalities, leading to a presumptive diagnosis of RTD, which was confirmed by histopathology. Karyotype analysis revealed 46,XX,dup(1)(q24.1q25.1), which was further confirmed by whole exome sequencing. The chromosomal abnormality did not involve RAS genes, and the remaining workup was unremarkable. Despite intensive medical management, the patient died on day 20 of life. The aim of this case report was to raise awareness of this severe kidney disorder, highlighting its atypical presentation, which lacked major cardiovascular dysfunction, showed no identifiable classic etiology despite thorough investigation, and revealed a de novo chromosomal abnormality. These findings suggest the involvement of alternative pathophysiologic mechanisms in RTD.

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