Pseudo-TORCH-Syndrom-3D84.9

Pseudo-TORCH syndrome-3, also known as PTORCH3, is an autosomal recessive disorder of immune dysregulation and neuroinflammation (caused by a missense mutation in the STAT2 gene) that occurs in early childhood. Affected individuals have developmental delay with acute febrile episodes and multisystemic organ involvement, including coagulopathy, elevated liver enzymes, and proteinuria, often associated with thrombotic microangiopathy.

The disorder results from defects in the negative regulation of the interferon immunological pathway. In 2 brothers born of consanguineous Pakistani parents with pseudo-TORCH PTORCH3, Duncan et al (2019) identified a homozygous missense mutation in the STAT2 gene. RNA and RT-PCR analyses of patient blood showed increased expression of IFN-stimulated genes (ISG), consistent with a type I interferonopathy.

In a boy born to consanguineous Moroccan parents with PTORCH3, Gruber et al. (2020) also identified a homozygous missense mutation in the STAT2 gene.

Brain imaging shows progressive intracranial calcifications, white matter abnormalities, and sometimes cerebral or cerebellar atrophy.

Abnormal elevation of interferon (IFN)-stimulated gene (ISG) transcripts consistent with type I interferonopathy .

Death in early childhood is common (summary by Duncan et al. 2019 and Gruber et al. 2020).

The acronym TORCH serves as a collective term for important infections in pregnancy. These include:

• Toxoplasmosis
• other (others like syphilis, listeriosis)
• Rubella
• Cytomegalovirus
• herpes simplex

1. Duncan CJA et al (2019) Severe type I interferonopathy and unrestrained interferon signaling due to a homozygous germline mutation in STAT2. Sci Immunol 4: eaav7501
2. Gruber C et al (2020) Homozygous STAT2 gain-of-function mutation by loss of USP18 activity in a patient with type I interferonopathy. J Exp Med 217: e20192319