Bengaluru: Paediatric specialists in the city have documented what is believed to be India’s first known case of pseudo-TORCH syndrome associated with the USP18 gene, an exceptionally rare genetic disorder seen in only a handful of children worldwide. The case, identified in an 11-year-old girl and treated at the state-run Indira Gandhi Institute of Child Health (IGICH), is also thought to be just the 12th recorded instance globally. A detailed case report was recently published in a Wolters Kluwer Health journal, marking a significant medical milestone for the country’s clinical genetics and paediatric neurology community.
Rare disorder mimics congenital infections
Pseudo-TORCH syndrome is a poorly defined autosomal recessive genetic condition that clinically resembles congenital TORCH infections — a group of infections transmitted from mother to foetus. Children with pseudo-TORCH present with symptoms such as microcephaly, seizures, developmental delays, intracranial calcifications and recurrent episodes of neurological dysfunction.
The disorder remains vastly underdiagnosed because of its similarity to infectious conditions and the limited access to advanced genetic testing, especially in low- and middle-income settings. Globally, only 11 cases linked to the USP18 gene — a gene involved in regulating the body’s antiviral immune response — have been confirmed before this report.
Child had long history of severe neurological symptoms
The 11-year-old patient, born to consanguineous parents, had a complex medical history beginning in infancy. Doctors said her elder sibling had died at just eight months from a similar neuro-inflammatory illness, raising early suspicion of an inherited condition.
The girl herself experienced her first episode of febrile encephalopathy with seizures at eight months — the same age at which her sibling had fallen ill. Over the years, she suffered repeated hospitalisations due to fever-triggered neurological relapses, developmental delays, learning difficulties and persistent cognitive challenges. Her family eventually discontinued her formal schooling after Class 3, as she struggled with basic arithmetic and letter recognition despite being able to perform daily activities independently.
Latest episode led to crucial genetic diagnosis
In her recent clinical episode, the child developed high-grade intermittent fever for 15 days, followed by a rash on her chest that gradually evolved into a lesion. When she was admitted to IGICH, clinicians found her drowsy but responsive, with retained memory and comprehension. They also observed distinct dysmorphic facial features, including arched eyebrows, a broad nasal bridge, bulbous nasal tip and a prominent chin.
A CT scan revealed intracranial calcifications, a classical hallmark of pseudo-TORCH conditions. However, her TORCH infection panel returned negative results, prompting doctors to proceed with exome sequencing, a comprehensive genetic test.
“Exome sequencing confirmed the diagnosis of USP18-related pseudo-TORCH syndrome,” a clinician involved in her care said.
Global survival rate extremely low
Discussing prognosis, doctors highlighted that of the 11 previously reported global cases, nine children had died, and only two survived beyond early childhood, underlining the disorder’s severity and the urgent need for early diagnosis.
The IGICH patient, however, has shown encouraging signs of stability under Baricitinib therapy, a Janus kinase (JAK) inhibitor commonly used as an anti-inflammatory agent. The child continues to remain under close medical follow-up with no new complaints reported since the initiation of the treatment.
Timely genetic testing critical, say neurologists
Dr Vykunta Raju Gowda, paediatric neurologist at IGICH and one of the lead clinicians managing the case, emphasised the importance of early genetic investigations.
“Timely genetic testing in children presenting with unexplained encephalopathy accompanied by intracranial calcification can significantly improve prognosis and guide more effective management,” he said.
He added that increasing awareness among paediatricians regarding rare genetic conditions can help reduce misdiagnosis and avoid unnecessary treatments targeted at infections.
Significance for Indian paediatrics and genetic research
Experts say this case not only adds to global medical literature but also underscores the growing importance of genomic medicine in India’s public healthcare system. With more tertiary centres adopting exome sequencing and precision-based diagnostics, clinicians now have better opportunities to identify rare genetic disorders that previously went undetected.
For the family, the diagnosis has provided long-awaited clarity. For clinicians, it has highlighted the need for establishing stronger rare-disease registries, improved surveillance and enhanced access to genetic counselling for high-risk families, especially those with histories of consanguineous marriage.
As the patient continues her treatment, doctors hope that the case will pave the way for a broader understanding of USP18-related disorders and better therapeutic approaches in the future.