Variations in aganglionic segment length of the enteric neural plexus in Mowat-Wilson syndrome.
OBJECTIVE
Patients with zinc finger homeo box 1B (ZFHX1B) mutations or deletions develop multiple congenital anomalies including Hirschsprung disease, known as Mowat-Wilson syndrome (MWS). In this study, we investigated variations in the enteric neural plexus abnormalities in MWS using morphometry-based histopathologic analysis.


METHODS
Seven patients with MWS (3 with mutations in exon 8 of ZFHX1B and 4 with deletions) who had undergone modified Duhamel's operations for Hirschsprung disease were examined. Surgically resected rectosigmoid specimens were analyzed morphometrically.


RESULTS
The length of the aganglionic segment was longer than 3 cm in all the patients with deletions. In 3 patients with mutations, the aganglionic region was not detected in the surgically resected specimens; however, the parameters of the ganglions and plexus were significantly smaller than those of controls (cloaca and aproctia), indicative of a transitional zone. Variation in the severity of pathological changes among the 3 patients with mutations was also noted.


CONCLUSIONS
The variations in myenteric plexus pathologies in MWS appear to be caused by both variations in ZFHX1B abnormalities and epigenetic factors.
Ishihara
Naoko
N
Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Shimada
Atsuyoshi
A
Kato
Junji
J
Niimi
Norihiro
N
Tanaka
Shuichi
S
Miura
Kiyokuni
K
Suzuki
Tatsuya
T
Wakamatsu
Nobuaki
N
Nagaya
Masahiro
M
D000886:Anthropometry; D002675:Child, Preschool; D012809:Colon, Sigmoid / Q000294:innervation* / Q000473:pathology; D005260:Female; D006627:Hirschsprung Disease / Q000473:pathology*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D012007:Rectum / Q000294:innervation* / Q000473:pathology; D012097:Repressor Proteins / Q000235:genetics; D000074165:Zinc Finger E-box Binding Homeobox 2
D018398:Homeodomain Proteins; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2