Redcliffe Labs has reported the discovery of a rare USP18 gene mutation associated with recurrent neurological decline in children. The findings, published in Clinical Dysmorphology, document a previously unreported variant, c.358C>T (p.Pro120Ser), expanding clinical understanding of Pseudo-TORCH syndrome type 2. The condition is often difficult to diagnose due to overlapping symptoms with infectious and metabolic disorders.
The clinical evaluation and ongoing management of the child were guided by diagnostic insights from Dr Himani Pandey, Lab Head, Genomics, Redcliffe Labs, along with Dr Vykuntaraju K. Gowda, Department of Paediatric Neurology, Indira Gandhi Institute of Child Health, Bengaluru.
The discovery originates from the case of an 11-year-old girl who displayed symptoms from infancy, including repeated episodes of febrile encephalopathy, seizures, delayed development, and microcephaly. Progressive brain scans showed calcium deposits across multiple regions. With only 11 known cases globally, this study adds to the limited body of evidence. The diagnosis was made through exome sequencing with mitochondrial genome sequencing, identifying the previously unknown USP18 gene variant after years of inconclusive evaluation.
Pseudo-TORCH syndrome type 2 is a rare inherited disorder affecting neurological development. Symptoms resemble congenital infections but occur without infection. The USP18 gene regulates immune response and prevents excessive inflammation. Mutations in this gene disrupt regulation, causing harmful immune overactivation affecting brain function.
The newly identified variant alters USP18 protein structure, weakening inflammatory control. This dysregulation may explain repeated neurological decline triggered by fever. Understanding this pattern supports timely recognition, reduces unnecessary infection-based treatments, and informs management focused on immune-related mechanisms.
Aditya Kandoi, Founder and CEO, Redcliffe Labs, said; “We believe the future of diagnostics lies in uncovering answers that were once thought impossible. This breakthrough is more than a scientific milestone; it demonstrates how advanced genomics, when paired with deep clinical insight, can fundamentally change a child’s trajectory. Discovering a novel USP18 variant is not just an academic achievement; it reflects our commitment to pushing the boundaries of precision medicine in India. Complex neurological conditions often leave families navigating uncertainty for years, and breakthroughs like this help bring clarity where it matters most. I am proud of our team and our collaborators for setting a new benchmark in rare disease diagnostics. This is the kind of work that strengthens India’s leadership in genomic innovation and moves us closer to a future where no medical mystery remains unsolved.”
Commenting on the findings, Dr Himani Pandey said; “We remain committed to expanding our specialised diagnostic capabilities to address some of the most challenging medical conditions seen in clinical practice. This case is also the first documented case of USP18-related disease presenting with recurrent febrile encephalopathy. The successful diagnosis reflects the depth of expertise our team brings through advanced tests such as exome sequencing. These capabilities enable us to solve complex and often long-standing medical mysteries. We applaud the research team’s achievement. This strengthens the role of Redcliffe Labs in advancing diagnostic precision and improving outcomes for patients with rare and difficult-to-diagnose conditions.”
The study contributes new clinical and genetic evidence to the limited global research on USP18-related disorders. The confirmed diagnosis supports improved long-term care planning and highlights the role of early genetic testing in unexplained paediatric neurological conditions. The findings also provide direction for future research and potential targeted care approaches.