Pathogenic variants in the IFT140 gene and an intriguing clinical presentation in two pediatric patients. Cases report and review of literature.

Abstract

Background: The IFT140 gene is one of many genes involved in the synthesis of proteins needed for cilium function. Ciliopathies are a group of disorders associated with the dysfunction of ciliary structures and express as an individual organ system disease as well as multisystem disorders. Dysfunctional cilia typically manifest as pleiotropic clinical features, reflecting their widespread distribution and varied functionality.

Cases presentation: We present two cases: Case 1, a male with two pathological variations in IFT140 gene, a compound heterozygote, with kidney failure, retinal dystrophy, cardiomyopathy, and situs inversus and Case 2, a female with an IFT140 pathogenic homozygous variant, presented with nephrotic range proteinuria, retinitis pigmentosa, and pseudotumor cerebri.

Conclusions: As cilia dysfunction is known to cause pleiotropic clinical features due to the presence of cilia in different organs in the body, the clinical picture of the IFT140 mutation is also very heterogeneous. Our cases reveal unprecedented manifestations - LVNC, situs inversus, and pseudotumor cerebri - not previously documented in IFT140 mutation. These findings underscore the importance of genetic screening in ciliopathies.