USP18 Deficiency Presenting as Severe Neonatal Encephalopathy: A Case Report and Review of Pseudo-TORCH Syndromes.

Pseudo-TORCH (Toxoplasma, "Other" agents, Rubella, Cytomegalovirus, Herpes simplex, etc.) syndromes are rare genetic disorders that mimic congenital TORCH infections but lack an infectious cause. Affected infants present with encephalopathy, intracranial calcifications, and congenital anomalies. We report a term male infant who developed catastrophic encephalopathy and coagulopathy on day eight of life, with neuroimaging showing hemorrhages, calcifications, and cortical malformations. Whole-exome sequencing revealed a homozygous splice-site mutation in USP18, confirming pseudo-TORCH syndrome type 2. Despite maximal intensive care, the infant succumbed at one month of age. This case illustrates the diagnostic challenges and rapid progression of USP18 deficiency, highlights the value of early genetic confirmation for family counseling, and reviews the spectrum of pseudo-TORCH syndromes. Emerging therapies targeting interferon pathways may offer future hope. Our literature review highlights the differential diagnoses and genetic variability among pseudo-TORCH conditions, which include mutations in OCLN, USP18, STAT2, and JAM3. This emphasizes the importance of early genetic confirmation for better prognosis and family counseling. Emerging therapies targeting the interferon pathway, such as Janus kinase (JAK) inhibitors, are currently under investigation and may offer hope for these previously untreatable disorders. This case underscores the necessity of considering pseudo-TORCH syndromes in neonates who present with unexplained encephalopathy and brain calcifications after infectious causes have been ruled out.