Expanding the clinical spectrum in trichohepatoenteric syndrome

Abstract

Trichohepatoenteric syndrome (THES) is a very rare autosomal recessive genetic disorder, which is characterized by intractable diarrhea during infancy, dysmorphic features, immunodeficiency, and a failure to thrive. There are still significant difficulties for patients and clinicians in terms of the management of THES, even though its molecular basis has been uncovered in the last decade. In this article, we have presented two cases relating to siblings that have been diagnosed with the condition.Concerning one of the patients, we described a novel variation (c.2114 + 5G > A) in the TTC37 gene and a mild clinical course; meanwhile, the other one was clinically diagnosed with THES at 17 years of age, but they had seizures and died suddenly. These cases expand the spectrum of clinical findings in relation to THES. K E Y W O R D S intractable diarrhea, trichohepatoenteric syndrome, TTC37 gene 1 | INTRODUCTION Trichohepatoenteric syndrome (THES) (OMIM #222470) is a rare genetic disorder that is characterized by intractable diarrhea that generally occurs in the neonatal period. Other clinical signs include woolly hair, intrauterine growth restriction, facial dysmorphism, immune deficiency, liver disease, skin abnormalities, cardiac abnormalities, and short stature (Fabre et al., 2017). Stankler et al. (1982) described THES for the first time in two siblings who had intractable diarrhea, intrauterine growth restriction, and facial dysmorphism; later, it was reported by Girault et al. (1994) that immune system

Chronic diarrhoea due to trichohepatoenteric syndrome (THES) in an infant

“…Trichohepatoenteric syndrome-1 (THES-1) is a rare autosomal recessive (AR) form of congenital syndromic diarrhoea with a reported incidence of 1:1 000 000 in Western literature 2. THES has been reported in fewer than 100 affected individuals worldwide 3. We report a case of THES in an infant, which expands our understanding of the approach to early diagnoses and treatment of similar disorders.…”

“…As seen in our case, genetic variants in the SKIC3 gene account for 70% of THES cases (THES 1), and the remaining 30% are due to SKIC2 gene variants (THES 2) 2. Characteristic features of THES include intractable diarrhoea during infancy (seen in almost all children), woolly or brittle hair (seen in all), intrauterine growth restriction, facial dysmorphism, immunodeficiency, low immune response, recurrent infections, skin abnormalities and liver disease 3 4. The characteristic clinical triad is intractable diarrhoea, facial dysmorphism and woolly hair with trichorrhexis nodosa.…”

“…In a review of all reported cases until 2017, 30% succumbed 1. Cases with pathogenic variants of the SKIC2 gene have higher mortality than SKIC3 3…”