# Pathology Seen in Myenteric Plexus in Two Subjects With Waardenburg Syndrome

## TL;DR

This study found reduced glial and ganglion cells in the gut of two infants with Waardenburg syndrome type 4, suggesting a link between the genetic condition and gut motility issues.

## Contribution

The study provides novel histological evidence of neuroglial abnormalities in the myenteric plexus of WS4 patients, linking genetic mutations to gut dysmotility.

## Key findings

- Subjects with PCWH and WSS showed reduced glial cells (SOX10) and ganglion cells (HuC/D) in the myenteric plexus.
- Aganglionosis with a skipped segment was observed in the WSS case but not in the PCWH case.
- Interstitial cells of Cajal (CD117) were unaffected in both WS4 subjects.

## Abstract

The aim was to assess the neuroglial compartment in the myenteric plexus of two subjects with genetically verified Waardenburg syndrome (WS) type 4 (WS4) and to compare the outcome with four “age‐matched” controls.

Gut samples from four control cases and from two newborn subjects with WS4, one with peripheral demyelinating neuropathy, dysmyelinating leukodystrophy, WS and Hirschprung disease (PCWH) (SOX10, c.769A>T, p.Lys257*) and one with Waardenburg‐Shah syndrome (WSS) (EDN3, c.472C>T,p.Arg158Cys)—were assessed histologically and immunohistochemically. Antibodies directed to glial cells (SOX10), ganglion cells (HuC/D), and interstitial cells of Cajal (CD117) were applied.

For the child with PCWH syndrome, both the small and large intestine showed a reduction in the number of glial cells (SOX10), in parallel with hypoganglionosis (HuC/D), when compared with “age‐matched” controls. In the child with WSS, a severe reduction in the number of glial cells (SOX10) was observed in both the small and large intestine accompanied by aganglionosis (HuC/D) with a skipped segment. The number of interstitial cells of Cajal (CD117) appeared unaffected in both PCWH and WSS cases.

A severe reduction of glial cells and a severe reduction or loss of ganglion cells (the number of cells assessed per unit length), were seen in our study subjects when compared with “age‐matched” controls. Contrary to the above the presence of Cajal cells was unaffected.

Ganglion cells immunohistochemically labeled with pan‐neuronal marker HuC/D in sections from ileum. Note the different number of stained cells in the myenteric plexus. A, control subject, B, patient with SOX10 mutation (hypoganglionosis) C, patient with EDN3 mutation (aganlionosis). Both patients diagnosed with Waardenburg syndrome type 4 including gut dysmotility.