New Delhi, Nov 27: A group of researchers from India has discovered a rare mutation in the USP18 gene that is associated with recurrent neurological deterioration in children.

This unique mutation provides vital insights into a neurological condition that has been documented in only 11 cases globally, marking its first identification in India. The research was conducted by the Indira Gandhi Institute of Child Health in Bangalore, in collaboration with Ramjas College, University of Delhi, and Redcliffe Labs.

Pseudo-TORCH syndrome type 2 is an extremely rare inherited disorder that impacts the development and functioning of a child's brain. Affected children often exhibit severe neurological symptoms that mimic congenital infections, despite the absence of any actual infection.

The USP18 gene plays a crucial role in regulating the immune response, preventing excessive inflammation. When this gene malfunctions, the immune system can become overly active, leading to damage in the brain.

The findings, published in the journal Clinical Dysmorphology, describe a previously unreported variant, c.358C>T (p.Pro120Ser), which enhances the clinical understanding of Pseudo-TORCH syndrome type 2.

Dr. Vykuntaraju K. Gowda from the Department of Pediatric Neurology at IGICH stated, "This discovery underscores the significance of clinical intuition supported by advanced genetic testing. For years, we managed symptoms without a clear diagnosis, but identifying this new USP18 mutation has not only clarified the diagnosis but also improved the child's prognosis.”

He further explained, “This finding will help us avoid unnecessary treatments, provide targeted therapies, and importantly, assist families with informed genetic counseling. Our research illustrates how timely genetic insights can alter the trajectory of rare neurological disorders, offering hope where previously there were none.”

The study began with an 11-year-old girl who exhibited symptoms from infancy, including recurrent febrile encephalopathy, characterized by fever-induced unconsciousness, seizures, developmental delays, and a smaller head size.

Over time, her brain scans revealed increasing calcium deposits in various regions. To uncover the root cause of her ongoing neurological issues, advanced genetic testing was advised. Utilizing a specialized DNA test known as exome sequencing combined with mitochondrial genome sequencing, the team identified a novel alteration in the USP18 gene, providing clarity after years of uncertainty.

This newly discovered mutation modifies the structure of the USP18 protein, diminishing its capacity to regulate inflammation. This heightened immune response may account for the child's recurrent episodes of fever-related neurological decline.

Recognizing this connection is crucial as it enables healthcare providers to identify early warning signs, avoid unnecessary treatments for infections, and concentrate on monitoring and managing conditions associated with immune overactivity.

Dr. Himani Pandey, another researcher involved, noted, "This case is the first documented instance of a USP18-related disease manifesting with recurrent febrile encephalopathy.”

The research emphasizes the necessity of early genetic testing in children with unexplained neurological symptoms and paves the way for more focused care strategies in the future.