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Trichohepatoenteric syndrome 2(THES2)

MedGen UID:
482919
Concept ID:
C3281289
Disease or Syndrome
Synonym: THES2
 
Gene (location): SKIC2 (6p21.33)
 
Monarch Initiative: MONDO:0013818
OMIM®: 614602

Disease characteristics

Excerpted from the GeneReview: Trichohepatoenteric Syndrome
Trichohepatoenteric syndrome (THES), generally considered to be a neonatal enteropathy, is characterized by intractable diarrhea (seen in almost all affected children), woolly hair (seen in all), intrauterine growth restriction, facial dysmorphism, and short stature. Additional findings include poorly characterized immunodeficiency, recurrent infections, skin abnormalities, and liver disease. Mild intellectual disability (ID) is seen in about 50% of affected individuals. Less common findings include congenital heart defects and platelet anomalies. To date 52 affected individuals have been reported. [from GeneReviews]
Authors:
Alexandre Fabre  |  Patrice Bourgeois  |  Charlène Chaix, et. al.   view full author information

Additional descriptions

From OMIM
Trichohepatoenteric syndrome-2 (THES2) is a rare and severe disease characterized by intrauterine growth retardation, facial dysmorphism, hair abnormalities, intractable diarrhea, and immunodeficiency (summary by Fabre et al., 2012). For a discussion of genetic heterogeneity of trichohepatoenteric syndrome, see THES1 (222470).  http://www.omim.org/entry/614602
From MedlinePlus Genetics
Trichohepatoenteric syndrome is often life-threatening in childhood, particularly in children who develop liver disease or severe infections.

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.

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.

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.  https://medlineplus.gov/genetics/condition/trichohepatoenteric-syndrome

Clinical features

From HPO
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Colitis
MedGen UID:
40385
Concept ID:
C0009319
Disease or Syndrome
Ulcerative colitis is a chronic disorder that affects the digestive system. This condition is characterized by abnormal inflammation of the inner surface (epithelium) of the rectum and colon. The rectum and colon make up most of the length of the large intestine. The inflammation usually causes open sores (ulcers) to develop in the large intestine. Ulcerative colitis usually appears between the age of 15 and 30, although it can develop at any age. The inflammation tends to flare up multiple times throughout a person's life, which causes recurring signs and symptoms.\n\nThe most common symptoms of ulcerative colitis are cramping abdominal pain and frequent diarrhea, often with blood, pus, or mucus in the stool. Other signs and symptoms include nausea, loss of appetite, bowel urgency, fatigue, and fevers. Chronic bleeding from the inflamed and ulcerated intestinal tissue can cause a shortage of red blood cells (anemia) in some affected individuals. People with this disorder have difficulty absorbing enough fluids and nutrients from their diet and often experience weight loss. Affected children usually grow more slowly than normal. Less commonly, ulcerative colitis causes problems with the skin, joints, eyes, kidneys, or liver, which are most likely due to abnormal inflammation.\n\nToxic megacolon is a rare complication of ulcerative colitis that can be life-threatening. Toxic megacolon involves a widening (dilation) of the colon and an overwhelming inflammatory response. Ulcerative colitis also increases the risk of developing colon cancer, especially in people whose entire colon is inflamed and in those who have had ulcerative colitis for 8 years or more.\n\nUlcerative colitis is one common form of inflammatory bowel disease (IBD). Another type of IBD, Crohn's disease, also causes chronic inflammation of the intestines. Unlike ulcerative colitis, which affects only the inner surface of the large intestine, Crohn's disease can cause inflammation in any part of the digestive system, and the inflammation extends deeper into the intestinal tissue.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Chronic hepatitis
MedGen UID:
9223
Concept ID:
C0019189
Disease or Syndrome
Hepatitis that lasts for more than six months.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Cirrhosis of liver
MedGen UID:
7368
Concept ID:
C0023890
Disease or Syndrome
A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function.
Bloody diarrhea
MedGen UID:
56232
Concept ID:
C0151594
Disease or Syndrome
Passage of many stools containing blood.
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Villous atrophy
MedGen UID:
154306
Concept ID:
C0554101
Finding
The enteric villi are atrophic or absent.
Immunodeficiency
MedGen UID:
7034
Concept ID:
C0021051
Disease or Syndrome
Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.
Decreased circulating iron concentration
MedGen UID:
65918
Concept ID:
C0235988
Finding
The concentration of iron in the blood circulation is below the lower limit of normal.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Trichorrhexis nodosa
MedGen UID:
82668
Concept ID:
C0263485
Disease or Syndrome
Trichorrhexis nodosa is the formation of nodes along the hair shaft through which breakage readily occurs. It is thus a focal defect in the hair fiber that is characterized by thickening or weak points (nodes) that cause the hair to break off easily. The result is defective, abnormally fragile hair.
Brittle hair
MedGen UID:
120480
Concept ID:
C0263490
Disease or Syndrome
Fragile, easily breakable hair, i.e., with reduced tensile strength.
Wooly hair
MedGen UID:
87469
Concept ID:
C0343073
Finding
The term wooly hair refers to an abnormal variant of hair that is fine, with tightly coiled curls, and often hypopigmented. Optical microscopy may reveal the presence of tight spirals and a clear diameter reduction as compared with normal hair. Electron microscopy may show flat, oval hair shafts with reduced transversal diameter.
Uncombable hair
MedGen UID:
348660
Concept ID:
C1860607
Finding
Hair that is disorderly, stands out from the scalp, and cannot be combed flat.
Sparse hair
MedGen UID:
1790211
Concept ID:
C5551005
Finding
Reduced density of hairs.
Premature birth
MedGen UID:
57721
Concept ID:
C0151526
Pathologic Function
The birth of a baby of less than 37 weeks of gestational age.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Recent clinical studies

Etiology

Alsaleem BM, Hasosah M, Ahmed ABM, Al Hatlani MM, Alanazi AH, Al-Hussaini A, Asery AT, Alghamdi KA, AlRuwaithi MM, Khormi MAM, Al Sarkhy A, Alshamrani AS
Saudi J Gastroenterol 2022 Mar-Apr;28(2):135-142. doi: 10.4103/sjg.sjg_200_21. PMID: 34414925Free PMC Article

Diagnosis

Ozturk M, Ates K, Esener Z, Mutlu H, Aydogmus C, Boztug K, Sarac H, Gezdirici A, Dogan M, Beser OF, Varol FI, Gokce IK, Ozdemir R, Tekedereli I
Mol Biol Rep 2024 Jun 14;51(1):736. doi: 10.1007/s11033-024-09656-6. PMID: 38874671
Lee KY, Bremner R, Hartley J, Protheroe S, Haller W, Johnson T, Whyte L
Am J Med Genet A 2024 Feb;194(2):141-149. Epub 2023 Sep 27 doi: 10.1002/ajmg.a.63409. PMID: 37753667
Alsaleem BM, Hasosah M, Ahmed ABM, Al Hatlani MM, Alanazi AH, Al-Hussaini A, Asery AT, Alghamdi KA, AlRuwaithi MM, Khormi MAM, Al Sarkhy A, Alshamrani AS
Saudi J Gastroenterol 2022 Mar-Apr;28(2):135-142. doi: 10.4103/sjg.sjg_200_21. PMID: 34414925Free PMC Article
Lee WS, Teo KM, Ng RT, Chong SY, Kee BP, Chua KH
Gene 2016 Jul 15;586(1):1-6. Epub 2016 Apr 12 doi: 10.1016/j.gene.2016.03.049. PMID: 27050310
Chong JH, Jamuar SS, Ong C, Thoon KC, Tan ES, Lai A, Aan MK, Tan WL, Foo R, Tan EC, Lau YL, Liew WK
Eur J Pediatr 2015 Oct;174(10):1405-11. Epub 2015 May 15 doi: 10.1007/s00431-015-2563-z. PMID: 25976726

Therapy

Busoni VB, Lemale J, Dubern B, Frangi F, Bourgeois P, Orsi M, Badens C, Fabre A
J Pediatr Gastroenterol Nutr 2017 Jan;64(1):37-41. doi: 10.1097/MPG.0000000000001218. PMID: 28027214

Prognosis

Duclaux-Loras R, Lebreton C, Berthelet J, Charbit-Henrion F, Nicolle O, Revenu des Courtils C, Waich S, Valovka T, Khiat A, Rabant M, Racine C, Guerrera IC, Baptista J, Mahe MM, Hess MW, Durel B, Lefort N, Banal C, Parisot M, Talbotec C, Lacaille F, Ecochard-Dugelay E, Demir AM, Vogel GF, Faivre L, Rodrigues A, Fowler D, Janecke AR, Müller T, Huber LA, Rodrigues-Lima F, Ruemmele FM, Uhlig HH, Del Bene F, Michaux G, Cerf-Bensussan N, Parlato M
J Clin Invest 2022 May 16;132(10) doi: 10.1172/JCI154997. PMID: 35575086Free PMC Article
Alsaleem BM, Hasosah M, Ahmed ABM, Al Hatlani MM, Alanazi AH, Al-Hussaini A, Asery AT, Alghamdi KA, AlRuwaithi MM, Khormi MAM, Al Sarkhy A, Alshamrani AS
Saudi J Gastroenterol 2022 Mar-Apr;28(2):135-142. doi: 10.4103/sjg.sjg_200_21. PMID: 34414925Free PMC Article
Vardi I, Barel O, Sperber M, Schvimer M, Nunberg M, Field M, Ouahed J, Marek-Yagel D, Werner L, Haberman Y, Lahad A, Anikster Y, Rechavi G, Barshack I, McElwee JJ, Maranville J, Somech R, Snapper SB, Weiss B, Shouval DS
Dig Dis Sci 2018 May;63(5):1192-1199. Epub 2018 Feb 26 doi: 10.1007/s10620-018-4983-x. PMID: 29484573Free PMC Article
Lee WS, Teo KM, Ng RT, Chong SY, Kee BP, Chua KH
Gene 2016 Jul 15;586(1):1-6. Epub 2016 Apr 12 doi: 10.1016/j.gene.2016.03.049. PMID: 27050310

Clinical prediction guides

Ozturk M, Ates K, Esener Z, Mutlu H, Aydogmus C, Boztug K, Sarac H, Gezdirici A, Dogan M, Beser OF, Varol FI, Gokce IK, Ozdemir R, Tekedereli I
Mol Biol Rep 2024 Jun 14;51(1):736. doi: 10.1007/s11033-024-09656-6. PMID: 38874671
Duclaux-Loras R, Lebreton C, Berthelet J, Charbit-Henrion F, Nicolle O, Revenu des Courtils C, Waich S, Valovka T, Khiat A, Rabant M, Racine C, Guerrera IC, Baptista J, Mahe MM, Hess MW, Durel B, Lefort N, Banal C, Parisot M, Talbotec C, Lacaille F, Ecochard-Dugelay E, Demir AM, Vogel GF, Faivre L, Rodrigues A, Fowler D, Janecke AR, Müller T, Huber LA, Rodrigues-Lima F, Ruemmele FM, Uhlig HH, Del Bene F, Michaux G, Cerf-Bensussan N, Parlato M
J Clin Invest 2022 May 16;132(10) doi: 10.1172/JCI154997. PMID: 35575086Free PMC Article
Vardi I, Barel O, Sperber M, Schvimer M, Nunberg M, Field M, Ouahed J, Marek-Yagel D, Werner L, Haberman Y, Lahad A, Anikster Y, Rechavi G, Barshack I, McElwee JJ, Maranville J, Somech R, Snapper SB, Weiss B, Shouval DS
Dig Dis Sci 2018 May;63(5):1192-1199. Epub 2018 Feb 26 doi: 10.1007/s10620-018-4983-x. PMID: 29484573Free PMC Article
Michaux G, Massey-Harroche D, Nicolle O, Rabant M, Brousse N, Goulet O, Le Bivic A, Ruemmele FM
Biol Cell 2016 Jan;108(1):19-28. Epub 2015 Dec 8 doi: 10.1111/boc.201500034. PMID: 26526116