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.

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.

Trichohepatoenteric syndrome can be caused by variants (also called mutations) in the SKIC3 or SKIC2 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.

Variants in the SKIC3 or SKIC2 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.

Genetic Testing Information

• Genetic Testing Registry: Trichohepatoenteric syndrome
• Genetic Testing Registry: Trichohepatoenteric syndrome 2

Genetic and Rare Diseases Information Center

• Syndromic diarrhea

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• TRICHOHEPATOENTERIC SYNDROME 1; THES1
• TRICHOHEPATOENTERIC SYNDROME 2; THES2

Scientific Articles on PubMed

• PubMed

• Fabre A, Andre N, Breton A, Broue 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. doi: 10.1002/ajmg.a.31634. Citation on PubMed
• 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. Citation on PubMed
• 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. Citation on PubMed or Free article on PubMed Central
• 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. Citation on PubMed or Free article on PubMed Central
• Fabre A, Martinez-Vinson C, Roquelaure B, Missirian C, Andre N, Breton A, Lachaux A, Odul E, Colomb V, Lemale J, Cezard 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. Citation on PubMed
• 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. Citation on PubMed or Free article on PubMed Central
• 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. doi: 10.1002/(sici)1096-8628(19970211)68:43.0.co;2-p. Citation on PubMed