TTC7A Variants Results in Gastrointestinal Defects and Immunodeficiency Syndrome: Case Series and Literature Review.

Abstract

Gastrointestinal Defects and Immunodeficiency Syndrome-1 (GIDID-1), caused by abnormalities in TTC7A, is an autosomal recessive disorder characterized by multiple gastrointestinal malformations and immune deficiencies, often accompanied by inflammatory bowel disease (IBD). This condition typically results in poor treatment outcomes and is usually fatal in early infancy. This paper examined the genetic abnormalities and clinical features of GIDID by analyzing data from three children and one fetus with gastrointestinal dysfunction and immune deficiency associated with TTC7A abnormalities at our hospital, and reviewed reported cases worldwide. Genetic analysis of the four patients identified eight novel variants in the TTC7A, five of which were likely pathogenic variants, while three were of uncertain significance. Including the cases reported in this paper and through a literature review, there were 89 known cases globally, involving 79 TTC7A variants. Patients typically presented with multiple gastrointestinal malformations, immune deficiencies, or IBD. Thus, genetic testing is recommended for patients with multiple gastrointestinal malformations and recurrent infections to determine if GIDID is due to TTC7A abnormalities. The syndrome generally has a poor prognosis, and this information is crucial for treatment planning, prenatal screening, and genetic counseling.