Recurrent fever-associated acute liver failure and cranial dysmorphism in children caused by RINT1 gene mutations: a rare case report

TL;DR

A rare case of liver failure and cranial abnormalities in a child is linked to mutations in the RINT1 gene.

Contribution

This case report expands the known phenotypic spectrum of ILFS3 by highlighting cranial dysmorphism as a feature.

Findings

Compound heterozygous RINT1 gene mutations were identified in a 9-month-old infant with recurrent fever-associated ALF.

The patient showed cranial dysmorphism and vertebral deformities, expanding the clinical features of ILFS3.

Early genetic diagnosis and antipyretic intervention may improve outcomes in such cases.

Abstract

Mutations in the RINT1 gene represent a rare genetic cause of recurrent fever-associated acute liver failure (ALF) accompanied by skeletal abnormalities in infants and children. We report the case of a 9-month-old infant presenting with multisystem involvement, primarily characterized by recurrent fever-associated ALF and cranial dysmorphism, due to compound heterozygous mutations in the RINT1 gene. The patient exhibited abnormal liver function tests and coagulation dysfunction following febrile episodes. Over a period of more than one year, the patient initially experienced two episodes of acute liver injury, followed by two episodes of ALF, with progressively worsening clinical manifestations. Whole-exome sequencing (WES) identified compound heterozygous variants in the RINT1 gene (exons 12–14 deletion; intron 11, c.1672-1G > T, p.?), consistent with a diagnosis of infantile liver failure syndrome-3 (ILFS3). Between episodes, liver function failed to return fully to baseline and was accompanied by growth retardation, delayed psychomotor development, cranial dysmorphism, and beak-like deformities of vertebral bodies. This case highlights the critical role of RINT1 mutations in the pathogenesis of recurrent fever-associated ALF and emphasizes the importance of recognizing associated skeletal developmental abnormalities, including cranial dysmorphism. Early genetic diagnosis and prompt antipyretic intervention may mitigate liver injury and improve long-term outcomes. By documenting cranial dysmorphism in this context, we aim to expand the recognized phenotypic spectrum of ILFS3 and improve clinical awareness among pediatricians and geneticists.

Figures