Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

Trichohepatoenteric syndrome

Reviewed March 2014

What is trichohepatoenteric syndrome?

Trichohepatoenteric syndrome is a condition that affects the hair (tricho-), liver (hepato-), and intestines (enteric), as well as other tissues and organs in the body. This condition is also known as syndromic diarrhea because chronic, difficult-to-treat diarrhea is one of its major features. Within the first few weeks of life, affected infants develop watery diarrhea that occurs multiple times per day. Even with nutritional support through intravenous feedings (parenteral nutrition), many of these children experience failure to thrive, which means they do not gain weight or grow at the expected rate. Most children with trichohepatoenteric syndrome are small at birth, and they remain shorter than their peers throughout life.

Abnormal hair is another feature of trichohepatoenteric syndrome. Hair in affected individuals is described as wooly, brittle, patchy, and easily pulled out. Under a microscope, some strands of hair can be seen to vary in diameter, with thicker and thinner spots. This feature is known as trichorrhexis nodosa.

Other signs and symptoms of trichohepatoenteric syndrome can include liver disease; skin abnormalities; and distinctive facial features, including a wide forehead, a broad base of the nose, and widely spaced eyes. Overall, the facial features are described as "coarse." Most affected individuals also experience immune system abnormalities that can make them prone to developing infections. Less commonly, trichohepatoenteric syndrome is associated with heart (cardiac) abnormalities. Mild intellectual disability has been reported in at least half of all children with the condition.

Trichohepatoenteric syndrome is often life-threatening in childhood, particularly in children who develop liver disease or severe infections.

How common is trichohepatoenteric syndrome?

Trichohepatoenteric syndrome is a rare condition with an estimated prevalence of about 1 in 1 million people. At least 44 cases have been reported in the medical literature.

What genes are related to trichohepatoenteric syndrome?

Trichohepatoenteric syndrome can be caused by mutations in the TTC37 or SKIV2L gene. These genes provide instructions for making proteins whose functions have not been confirmed. Researchers speculate that they work together with other proteins within cells to help recognize and break down excess or abnormal messenger RNA (mRNA) molecules. mRNA is a chemical cousin of DNA that serves as the genetic blueprint for protein production. Studies suggest that getting rid of excess and abnormal mRNA is important for cell growth.

Mutations in the TTC37 or SKIV2L gene likely eliminate the function of their respective proteins, which is hypothesized to impair the breakdown of unneeded mRNA. However, it is unknown how these changes could lead to chronic diarrhea and the other features of trichohepatoenteric syndrome.

Related Gene(s)

Changes in these genes are associated with trichohepatoenteric syndrome.

  • SKIV2L
  • TTC37

How do people inherit trichohepatoenteric syndrome?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of trichohepatoenteric syndrome?

These resources address the diagnosis or management of trichohepatoenteric syndrome and may include treatment providers.

  • American Society for Parenteral and Enteral Nutrition: What is Parenteral Nutrition? (http://www.nutritioncare.org/About_Clinical_Nutrition/What_is_Parenteral_Nutrition/)
  • Genetic Testing Registry: Trichohepatoenteric syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1857276)
  • Genetic Testing Registry: Trichohepatoenteric syndrome 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C3281289)
  • Health Topic: Nutritional Support (http://www.nlm.nih.gov/medlineplus/nutritionalsupport.html)

You might also find information on the diagnosis or management of trichohepatoenteric syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/trichohepatoenteric-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/trichohepatoenteric-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about trichohepatoenteric syndrome?

You may find the following resources about trichohepatoenteric syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for trichohepatoenteric syndrome?

  • diarrhea, fatal infantile, with trichorrhexis nodosa
  • diarrhea, syndromic
  • intractable diarrhea with phenotypic anomalies
  • phenotypic diarrhea of infancy
  • SD/THE
  • syndromic diarrhea
  • THES
  • THE syndrome
  • tricho-hepato-enteric syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about trichohepatoenteric syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding trichohepatoenteric syndrome?

autosomal ; autosomal recessive ; breakdown ; cardiac ; cell ; chronic ; diameter ; disability ; DNA ; enteric ; failure to thrive ; gene ; immune system ; inherited ; messenger RNA ; mRNA ; parenteral nutrition ; prevalence ; protein ; recessive ; RNA ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Fabre A, André N, Breton A, Broué P, Badens C, Roquelaure B. Intractable diarrhea with "phenotypic anomalies" and tricho-hepato-enteric syndrome: two names for the same disorder. Am J Med Genet A. 2007 Mar 15;143A(6):584-8. (http://www.ncbi.nlm.nih.gov/pubmed/17318842?dopt=Abstract)
  • Fabre A, Breton A, Coste ME, Colomb V, Dubern B, Lachaux A, Lemale J, Mancini J, Marinier E, Martinez-Vinson C, Peretti N, Perry A, Roquelaure B, Venaille A, Sarles J, Goulet O, Badens C. Syndromic (phenotypic) diarrhoea of infancy/tricho-hepato-enteric syndrome. Arch Dis Child. 2014 Jan;99(1):35-8. doi: 10.1136/archdischild-2013-304016. Epub 2013 Oct 9. (http://www.ncbi.nlm.nih.gov/pubmed/24108068?dopt=Abstract)
  • Fabre A, Charroux B, Martinez-Vinson C, Roquelaure B, Odul E, Sayar E, Smith H, Colomb V, Andre N, Hugot JP, Goulet O, Lacoste C, Sarles J, Royet J, Levy N, Badens C. SKIV2L mutations cause syndromic diarrhea, or trichohepatoenteric syndrome. Am J Hum Genet. 2012 Apr 6;90(4):689-92. doi: 10.1016/j.ajhg.2012.02.009. Epub 2012 Mar 22. (http://www.ncbi.nlm.nih.gov/pubmed/22444670?dopt=Abstract)
  • Fabre A, Martinez-Vinson C, Goulet O, Badens C. Syndromic diarrhea/Tricho-hepato-enteric syndrome. Orphanet J Rare Dis. 2013 Jan 9;8:5. doi: 10.1186/1750-1172-8-5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/23302111?dopt=Abstract)
  • Fabre A, Martinez-Vinson C, Roquelaure B, Missirian C, André N, Breton A, Lachaux A, Odul E, Colomb V, Lemale J, Cézard JP, Goulet O, Sarles J, Levy N, Badens C. Novel mutations in TTC37 associated with tricho-hepato-enteric syndrome. Hum Mutat. 2011 Mar;32(3):277-81. doi: 10.1002/humu.21420. Epub 2011 Feb 17. (http://www.ncbi.nlm.nih.gov/pubmed/21120949?dopt=Abstract)
  • Hartley JL, Zachos NC, Dawood B, Donowitz M, Forman J, Pollitt RJ, Morgan NV, Tee L, Gissen P, Kahr WH, Knisely AS, Watson S, Chitayat D, Booth IW, Protheroe S, Murphy S, de Vries E, Kelly DA, Maher ER. Mutations in TTC37 cause trichohepatoenteric syndrome (phenotypic diarrhea of infancy). Gastroenterology. 2010 Jun;138(7):2388-98, 2398.e1-2. doi: 10.1053/j.gastro.2010.02.010. Epub 2010 Feb 20. (http://www.ncbi.nlm.nih.gov/pubmed/20176027?dopt=Abstract)
  • Verloes A, Lombet J, Lambert Y, Hubert AF, Deprez M, Fridman V, Gosseye S, Rigo J, Sokal E. Tricho-hepato-enteric syndrome: further delineation of a distinct syndrome with neonatal hemochromatosis phenotype, intractable diarrhea, and hair anomalies. Am J Med Genet. 1997 Feb 11;68(4):391-5. (http://www.ncbi.nlm.nih.gov/pubmed/9021008?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: March 2014
Published: December 22, 2014