Renal Hypoplasia and Oligomeganephronia in a Fetus with Wolf–Hirschhorn Syndrome

TL;DR

This paper describes a fetus with Wolf–Hirschhorn syndrome and rare kidney abnormalities, offering insights into the condition's renal pathology.

Contribution

The study provides the first histological evidence of oligomeganephronia in a fetus with Wolf–Hirschhorn syndrome.

Findings

Renal hypoplasia in the fetus was associated with oligomeganephronia, including a thinned cortex and reduced glomeruli.

Larger 4p deletions may correlate with distinct histological patterns of kidney development in Wolf–Hirschhorn syndrome.

Abstract

Background and Clinical Significance: Wolf–Hirschhorn syndrome (WHS, OMIM #194190) is caused by deletion of the distal short arm of chromosome 4. It is characterized by intrauterine growth restriction (IUGR), developmental delay, epilepsy, distinctive facial features, and urinary tract anomalies, particularly renal hypoplasia. However, the histological profile of renal involvement in WHS is rarely documented. Case presentation: We report a case of fetal WHS with renal hypoplasia and histological evidence of oligomeganephronia (OMN). At 21 weeks’ gestation, a prenatal ultrasound revealed oligo/anhydramnios and IUGR. Genetic testing (karyotype and CGH-array) confirmed a de novo 17.92 Mb terminal deletion from 4p16.3 to 4p15.31. The pregnancy was legally terminated at 23 weeks. The autopsy showed characteristic WHS dysmorphisms, growth restriction, and markedly small kidneys. Histology revealed OMN with a thinned renal cortex with reduced glomeruli, mainly hypoplastic, some of which were hypertrophic, and dilated proximal tubules. Scattered medullary tubules were present within the tubulointerstitial compartment, alongside thickened tubular basement membranes highlighted by Collagen IV staining. Conclusions: This case suggests that OMN may be a histological hallmark of renal hypoplasia in WHS, especially in larger 4p deletions. Recognizing this pattern may help with prenatal prognosis and clinical management. Further studies are needed to confirm this association.

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