Impaired lymphatic drainage in a child with hydrops fetalis and a novel variant in the PROX1 gene: case report and review of literature.

PROX1 is a gene that encodes a protein that may play a key role in the development of the lymphatic system. This report describes impaired lymphatic drainage, with non-immune hydrops fetalis, congenital bilateral chylothorax, chylous ascites, and the need for peritoneal dialysis in a preterm neonate born at 32 weeks of gestation. The child died at about seven months of life. Clinical Exome Sequencing revealed the novel heterozygous variant c.502C > T in the PROX1 gene, which determines the change p.Arg168Trp at the protein level. This de novo missense variant was not detected in the analyzed parental DNA samples and has not been previously described in the literature. Although the identified PROX1 variant represents a biologically plausible contributor to the phenotype, causality cannot currently be established, and additional environmental or maternal factors cannot be excluded. Identifying this variant in affected individuals can have implications for perinatal and postnatal management and genetic counseling. To the best of our knowledge, this is the first case reported of a child carrier of a PROX1 variant with hydrops fetalis. PROX1 screening could be requested in prenatal diagnosis of hydrops fetalis and included in Next-Generation DNA Sequencing panels.