Redcliffe Labs has identified a rare USP18 gene mutation associated with recurrent neurological deterioration in children. The findings, published in Clinical Dysmorphology, describe a previously unreported variant, c.358C>T (p.Pro120Ser), significantly expanding the clinical understanding of Pseudo-TORCH syndrome type 2—a condition often misdiagnosed due to its similarity to infectious and metabolic disorders.
Breakthrough Driven by Collaborative Clinical Expertise
As reported by Express Healthcare, the diagnostic evaluation and ongoing management of the patient were guided by Dr Himani Pandey, Lab Head, Genomics, Redcliffe Labs, and Dr Vykuntaraju K. Gowda, Department of Paediatric Neurology, Indira Gandhi Institute of Child Health, Bengaluru. Their combined expertise enabled accurate diagnosis after years of inconclusive assessments.
Case of an 11-Year-Old Reveals New Clinical Insights
The discovery emerged from the case of an 11-year-old girl who had shown symptoms since infancy. She experienced repeated febrile encephalopathy, seizures, developmental delays, and microcephaly. Over time, brain imaging revealed progressive calcium deposits in multiple regions. With only 11 similar cases reported worldwide, this study adds valuable evidence to a very limited pool of knowledge.
Using exome sequencing with mitochondrial genome sequencing, clinicians identified the novel USP18 variant after years of uncertainty, establishing the first confirmed diagnosis of its kind.
Understanding Pseudo-TORCH Syndrome Type 2
Pseudo-TORCH syndrome type 2 is a rare inherited neurological disorder. Although the symptoms mimic congenital infections, no infection is present. The USP18 gene plays a crucial role in regulating immune responses and preventing excessive inflammation.
Mutations in this gene disrupt immune regulation, causing harmful overactivation that damages the brain. The newly discovered variant alters the USP18 protein structure, reducing its ability to control inflammation. This likely explains the child’s recurrent neurological decline during fever episodes.
Impact on Clinical Care and Diagnosis
Recognising this mutation helps clinicians identify similar cases earlier, minimising unnecessary infection-related treatments. Furthermore, it shifts management strategies toward immune-focused interventions, offering clearer pathways for long-term care.
Leaders Highlight Importance of Precision Diagnostics
Aditya Kandoi, Founder and CEO of Redcliffe Labs, said the discovery underscores the transformative role of advanced genomics. He emphasised that uncovering novel genetic variants not only advances science but also brings clarity to families facing complex neurological conditions. He added that such breakthroughs strengthen India’s leadership in genomic innovation.
Commenting on the findings, Dr Himani Pandey noted that this case represents the first documented instance of USP18-related disease presenting with recurrent febrile encephalopathy. She highlighted the crucial role of sophisticated testing, such as exome sequencing, in solving complex medical mysteries and improving diagnostic precision for rare diseases.
Strengthening Global Understanding of USP18 Disorders
The study adds new clinical and genetic evidence to the limited global research on USP18-related disorders. It reinforces the value of early genetic testing in unexplained paediatric neurological cases and provides direction for future research, potential targeted therapies, and improved long-term management strategies.