USP18 gene mutation associated with recurrent encephalopathy, intracranial calcification, and microcephaly: case report, long-term follow-up, and literature review.

INTRODUCTION

Pseudo-TORCH syndrome type 2 is a rare autosomal recessive disorder caused by biallelic variants in the USP18 gene. Clinically, affected individuals exhibit multisystem involvement, including intracranial calcification (ICC) and haemorrhage, seizures, hepatosplenomegaly, and thrombocytopenia. To date, only 11 cases have been reported in the literature.

CASE REPORT: We report a case of an Indian girl child born to consanguineous parents, presenting with recurrent febrile encephalopathy, developmental delay, microcephaly, tone abnormalities, organomegaly, thrombocytopenia, and ICCs. A similar clinical history was noted in the elder sibling who succumbed to the same illness.

RESULTS

Exome sequencing revealed a novel homozygous missense variant, c.358C>T (p.Pro120Ser), in exon four of the USP18 gene. Sanger sequencing of the asymptomatic parents confirmed heterozygosity of this variant.

CONCLUSION

To our knowledge, this is the first reported case of USP18 -related disease presenting with recurrent febrile encephalopathy. Further studies are required to understand better the variable presentations associated with the disease.