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A New Genetic Mutation in a Patient With Syndromic Diarrhea and Hepatoblastoma

Bozzetti, Valentina*; Bovo, Giorgio; Vanzati, Alice; Roggero, Paola; Tagliabue, Paolo E.*

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Journal of Pediatric Gastroenterology and Nutrition: September 2013 - Volume 57 - Issue 3 - p e15
doi: 10.1097/MPG.0b013e31825600c4
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A small-for-gestational-age preterm infant presented with prominent forehead and cheeks, broad nasal root, hypertelorism, and woolly and brittle hair. Intractable diarrhea began at 1 month. Upper endoscopy showed no abnormality, and histology showed mild and nonspecific villous atrophy with a normal brush border (Fig. 1). Microscopic analysis of the hair shaft revealed trichorrhexis nodosa (twisted hair, longitudinal breaks, cuticolar cell disruption) (Fig. 2). She died after 12 months from hepatic failure. Autopsy revealed a multinodular liver, with fibrosis and a macrotrabecluar-type hepatoblastoma (an area of immature hepatic cells arranged in trabecular structures and ribbons with intraluminar bilious thrombi) (Fig. 3).

Microscopic findings. Semithin slide under optical microscope shows a short intestinal villus.
Hair findings. Microscopic analysis of a hair shaft reveals abnormalities, including twisted hair (pili torti), longitudinal breaks, and cuticolar cell disruptions leading to the separation and fragmentation of the cortical fibers with the formation of nodes. These features are pathognomonic of trichorrhexis nodosa.
Postmortem liver histology. A small hepatic nodule showing macrotrabecular structure, resembling a degeneration area of hepatoblastoma and cirrhosis.

We suspected trichohepatoenteric syndrome (THES), a congenital entheropathy causing diarrhea in infants born small for gestational age. The syndrome is associated with nonspecific villous atrophy, facial dysmorphism, immune disorders, liver disease, and trichorrhexis nodosa (1). Hartley et al (2,3) identified the THES locus mapped to 5q14.3–5q21.2. A new homozygous mutation of the THES locus was identified in our patient (C2921-2G>A, skipping of the exon 29). This mutation, together with the occurrence of hepatoblastoma, has not been previously reported.


We thank Dr Antonello Villa of Milano-Bicocca University for the electronic microscopy, Prof ssa Margherita Silengo of Turin University for the evaluation of the hair shaft, Dr ssa Francesca Crosti and the genetic laboratory of San Gerardo Hospital for genetic supervision, Prof Jane Hartley of Birmingham Children's Hospital for the genetical analysis, and the medical and nursing staff of San Gerardo's NICU for the attention and the care paid to this patient.


1. Goulet O, Vinson C, Roquelaure B, et al. Syndromic (phenotypic) diarrhea in early infancy. Orphanet J Rare Dis 2008; 28:3–6.
2. Hartley JL, Zachos NC, Dawood B, et al. Mutations in TTC37 cause trichoepatoenteric syndrome (phenotypic diarrhea of infancy). Gastroenterology 2010; 138:2388–2398.
3. Fabre A, Martinez-Vinson C, Roquelaure B, et al. Novel mutations in TTC37 associated with tricho-hepato-enteric syndrome. Hum Mutat 2011; 32:277–281.
© 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,