New Delhi, Nov 27 (NationPress) A group of Indian researchers has uncovered a rare mutation in the USP18 gene linked to recurrent neurological decline in children.

This unique USP18 gene mutation provides vital insights into a neurological disorder that has only been documented in 11 cases globally and is now reported for the first time in India. The research was conducted by a team from 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 condition that impacts how a child's brain develops and operates. Youngsters affected by this disorder commonly exhibit severe neurological symptoms resembling congenital infections, although no actual infection is present.

The USP18 gene typically plays a role in regulating the body's immune response, preventing excessive inflammation. When this gene malfunctions, the immune system can become hyperactive, leading to damage in the brain.

The study, published in the journal Clinical Dysmorphology, documented a previously unidentified variant, c.358C>T (p.Pro120Ser), which expands the clinical understanding of Pseudo-TORCH syndrome type 2.

Dr. Vykuntaraju K. Gowda from the Department of Pediatric Neurology at Indira Gandhi Institute of Child Health stated, "This discovery emphasizes the importance of clinical intuition supported by advanced genetic testing. For years, we treated symptoms without a clear answer, but identifying this novel USP18 mutation has not only changed the diagnosis but also transformed the child’s future.”

He added, “This finding will allow us to avoid unnecessary treatments, provide precise therapy, and most importantly, guide families through informed genetic counseling. Our research demonstrates how timely genetic insights can alter the trajectory of rare neurological disorders, offering hope where answers were previously elusive."

The study began with an 11-year-old girl who started displaying symptoms from infancy, including recurrent episodes of febrile encephalopathy, characterized by fever-linked unconsciousness, seizures, delayed development, and a smaller head size.

Over time, imaging scans revealed increasing calcium deposits in various regions of her brain.

To uncover the cause of these recurring neurological issues, advanced genetic testing was recommended. By employing a focused DNA test known as exome sequencing combined with mitochondrial genome sequencing, the team discovered a previously unknown alteration in the USP18 gene, providing clarity after years of uncertainty.

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

Recognizing this linkage is vital as it aids physicians in identifying early warning signs, avoiding unnecessary treatments for infections, and concentrating on monitoring and managing conditions associated with immune overactivation.

“This case marks the first documented instance of a USP18-related disease manifesting with recurrent febrile encephalopathy,” noted Dr. Himani Pandey, one of the researchers.

The research underscores the significance of early genetic testing for children exhibiting unexplained neurological symptoms and paves the way for more targeted care strategies in the future.