Neonatal Noonan syndrome with acute kidney injury and systemic capillary leak syndrome caused by a RIT1 variant: a case report and literature review.

OBJECTIVE

To report a rare case of neonatal Noonan syndrome (NS) caused by a RIT1 c.247A>C (p.Thr83Pro), and to expand the understanding of life-threatening presentations in neonatal RIT1 associated NS.

METHODS

The clinical data of a neonate with NS admitted to the Neonatal Intensive Care Unit of Wuhan Children's Hospital were retrospectively analyzed, and Vitro functional studies were performed to investigate the pathogenic mechanism of the variant. A literature review of RIT1-NS cases reported between 2014 and 2025 was also performed.

RESULTS

The proband was a term female neonate presenting with progressive acute kidney injury (AKI), systemic capillary leak syndrome (SCLS), refractory chylothorax, and a large patent ductus arteriosus. Whole-exome sequencing identified a de novo heterozygous RIT1:c.247A>C p.(Thr83Pro). Functional studies revealed that this variant significantly enhanced the phosphorylation of ERK, JNK, and p38, and markedly upregulated IL-1β, IL-6, and TNF-α mRNA expression. Among 54 reported RIT1-NS cases, the p. Thr83Pro variant accounted for 3.7% (2/54); our case was the only one presenting with AKI and SCLS. Among the reported neonatal cases, 4 of 10 died during the neonatal period.

CONCLUSION

The RIT1:c.247A>C p.(Thr83Pro) might contribute to life-threatening NS in the neonatal period, and that early genetic testing may facilitate diagnosis and prognostic assessment.