A Novel Familial Case Report of Genetic Syndrome Mimicking Congenital TORCH infections; Pseudo-TORCH Syndrome 2

Iram Sehrish; Tella Sunitha; Avvari Srilekha; Aayushi Gupta; Pratibha Nallari; Ananthapur  Venkateshwari

doi:10.18502/jri.v23i2.8999

Iram Sehrish Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Telangana, India
Tella Sunitha Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Telangana, India
Avvari Srilekha Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Telangana, India
Aayushi Gupta Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Telangana, India
Pratibha Nallari Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Telangana, India
Ananthapur Venkateshwari Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Telangana, India

DOI: https://doi.org/10.18502/jri.v23i2.8999

Keywords: Next generation sequencing, Prenatal diagnosis, Pseudo-TORCH syndrome 2, Type I inter-feron signal transduction, Ubiquitin-specific peptidase 18.

Abstract

Background: Pseudo-TORCH syndrome (PTS) is a group of autosomal recessive disorders that clinically and radiologically mimic TORCH congenital infections. The prevalence of pseudo-TORCH syndrome 2 is 1 in 1,000,000 cases worldwide. This novel disorder is extremely rare, and is generally detected by prenatal diagnosis through next generation sequencing (NGS) during pregnancy. In this study, a familial case of pseudo-TORCH syndrome 2 with novel non-sense mutation in the ubiquitin-specific peptidase 18 (USP 18) gene in the parents was reported, who are heterozygous asymptomatic carriers; however, all children have inherited a homozygous pathogenic form of USP18, which is an important negative regulator of type I interferon (IFN) signal transduction. To the best of our knowledge, this is the first case of a novel mutation of USP18 seen in a family with pseudo-TORCH syndrome 2 (PTS 2) from India.

Case Presentation: A 23-year-old pregnant woman with bad obstetric history, including intrauterine and neonatal mortality was referred to the Institute of Genetics in the year 2021 for clinical and genetic evaluation. Advanced clinical exome sequencing of the parents and the fetus revealed heterozygous carrier status in parents and homozygous mutation in USP 18 gene in the progeny leading to pseudo-TORCH-2 syndrome.

Conclusion: The present case highlights the significance of carrier screening, prenatal diagnosis, and genetic counseling in couples with bad obstetric history for the detection of rare genetic disorders with poor prognosis.