Although the spectrum of phenotypic expression in trichohepatoenteric syndrome (THES) is broad, the characteristic features include intrauterine growth retardation, woolly hair, facial dysmorphism, intractable diarrhea in infancy requiring total parenteral nutrition, and immunodepression. Hepatic involvement contributes to the poor prognosis of affected patients (summary by Fabre et al., 2007).
Genetic Heterogeneity of Trichohepatoenteric Syndrome
Trichohepatoenteric syndrome-2 (THES2; 614602) is caused by mutation in the SKIV2L gene (SKIC2; 600478) on chromosome 6p21.
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Bourgeois et al. (2018) analyzed a cohort of 96 patients with THES from 85 different families, drawing from published reports (37 patients) and their own recruitment (59 patients). Approximately two-thirds of the patients carried biallelic TTC37 mutations, and one-third had SKIVL2 mutations; in 8 (8.3%) of the patients, only 1 mutation could be identified. Intractable diarrhea was present in 100% of patients regardless of genotype, with hair abnormalities (woolly, brittle, easily removable) present in 90%. Facial dysmorphisms were observed in 84% of clinically described patients, comprising primarily large forehead, broad nasal root, and hypertelorism. Intrauterine growth retardation was frequent, seen in 70% of TTC37-mutated patients and 86% of SKIV2L-mutated patients; however, there was no significant difference in postnatal growth between the 2 groups. Liver disease was common, and more frequent in patients with mutation in SKIV2L (88%) than in TTC37 (51%); findings ranged from elevated liver enzymes and hepatomegaly to fibrosis and cirrhosis. Immunodeficiency was reported in about half of clinically explored patients, presenting as low immunoglobulin count or lack of antibody response to immunization. In addition, approximately 40% to 50% of patients exhibited dermatologic abnormalities, mostly cafe-au-lait spots located on the lower limbs. Overall, the authors noted that THES patients with mutation in either gene exhibit remarkably similar clinical signs, involving primarily the gastrointestinal tract, hair, and face, and are indistinguishable in clinical practice. However, a few differences emerged from analysis of the cohort, with SKIV2L-associated THES showing an earlier onset and/or greater severity, with more severe liver disease and significantly smaller height and weight at birth. [from
OMIM]