Tricho-hepatic-enteric syndrome (THES) is a genetically heterogeneous rare syndrome (OMIM: 222470 (THES1) and 614602 (THES2)) that typically presents in the neonatal period with intractable diarrhoea, intra-uterine growth retardation (IUGR), facial dysmorphism, and hair and skin changes. THES is associated with pathogenic variants in either TTC37 or SKIV2L; both are components of the human SKI complex, an RNA exosome cofactor. We report an 8 year old girl who was diagnosed with THES by the Undiagnosed Disease Program-WA with compound heterozygous pathogenic variants in SKIV2L. While THES was considered in the differential diagnosis, the absence of protracted diarrhoea delayed definitive diagnosis. We therefore suggest that SKIV2L testing should be considered in cases otherwise suggestive of THES, but without the characteristic diarrhoea. We expand the phenotypic spectrum while reviewing the current knowledge on SKIV2L.
Bibliographical noteFunding Information:
This review and corresponding Gene Wiki article are written as part of the Gene Wiki review series – a series resulting from a collaboration between the journal GENE and the Gene Wiki Initiative. The Gene Wiki Initiative is supported by the National Institutes of Health (GM089820). Additional support for Gene Wiki reviews is provided by Elsevier, the publisher of GENE. The authors would like to thank the patient and her family for participation of the study and the Raine clinical research fellowship for support of DA.
DA was supported by a Raine Medical Research Foundation clinical research fellowship ( CRF018 , project “Diagnostic genomics applications for short stature”).
The Undiagnosed Disease Program (WA) is supported by the Angela Wright Bennet Foundation and McCusker Charitable Foundation.
- Next generation sequencing
- RNA exosome
- SKI complex