Acute Kidney Injury and Systemic Capillary Leak Syndrome in a Neonate

Background

Noonan syndrome (NS) is an autosomal dominant disorder with a significant incidence in neonates, often leading to serious complications. RIT1 variants account for a notable percentage of NS cases, and understanding their clinical presentations is crucial for timely diagnosis and management.

Data Highlights

The proband was a term female neonate with the following clinical features:

• Progressive acute kidney injury (AKI)
• Systemic capillary leak syndrome (SCLS)
• Refractory chylothorax
• Large patent ductus arteriosus

Key Findings

• The neonate was diagnosed with RIT1-associated Noonan syndrome (RIT1-NS) due to the variant RIT1:c.247A>C (p.Thr83Pro).
• This variant accounted for 3.7% of reported RIT1-NS cases, with the proband being the only one presenting with AKI and SCLS.
• Among 54 reported RIT1-NS cases, 4 out of 10 neonatal cases resulted in death during the neonatal period.
• Functional studies indicated that the RIT1 variant significantly enhanced phosphorylation of ERK, JNK, and p38, and upregulated inflammatory cytokines.
• Early genetic testing may facilitate diagnosis and prognostic assessment in similar cases.

Clinical Implications

Clinicians should consider the potential for severe presentations of Noonan syndrome in neonates with RIT1 variants.

Conclusion

The case highlights the critical need for awareness of the severe manifestations of RIT1-NS in neonates.

Related Resources & Content

1. Author(s)/Org, Source, Year -- Title
2. Frontiers in Medicine — Early continuous renal replacement therapy for acute kidney injury in a very low birth weight infant: a case report and literature review
3. Frontiers in Pediatrics — A case report of neonatal renal pseudohypoaldosteronism type I caused by a de novo variant in the NR3C2 gene
4. Frontiers in Pediatrics — Multisystem Hemorrhage in a Very Preterm Infant Born to a Mother with Immune Thrombocytopenia: A Case Report and Literature Review
5. Frontiers in Endocrinology — Coexistence of 21-Hydroxylase Deficiency and Gitelman Syndrome in a Neonate Presenting With Severe Hyponatremic Seizures: A Case Report
6. Early continuous renal replacement therapy for acute kidney injury in a very low birth weight infant: a case report and literature review
7. A case report of neonatal renal pseudohypoaldosteronism type I caused by a de novo variant in the NR3C2 gene
8. Multisystem Hemorrhage in a Very Preterm Infant Born to a Mother with Immune Thrombocytopenia: A Case Report and Literature Review
9. Noonan Syndrome - GeneReviews®
10. Acute kidney injury in neonates | Intensive Care Medicine – Paediatric and Neonatal
11. https://www.thieme-connect.com/products/ejournals/pdf/10.1055/a-2770-4952.pdf
12. NM_006912.6(RIT1):c.247A>C (p.Thr83Pro) AND Noonan syndrome 8 - ClinVar - NCBI
13. Neonatal Acute Kidney Injury: Diagnosis, Recognition and Prevention - ScienceDirect
14. Topic
15. Goal-directed Perfusion to Reduce Acute Kidney Injury After Pediatric Cardiac Operation - PubMed
16. Systemic capillary leak syndrome: a nosological entity that the nephrologist must be aware of
17. Idiopathic systemic capillary leak syndrome and related shock in PICU: an underdiagnosed disease? - PubMed
18. Frontiers | Thoracic fluid content as a novel and rapid diagnostic indicator of secondary capillary leak syndrome in pediatric patients post-cardiopulmonary bypass
19. Frontiers | The clinical application of subcutaneous thoracic ratio and capillary leakage index on the occurrence of capillary leak syndrome in neonates with sepsis