Abstract
Background: Galloway-Mowat syndrome is a rare neurodevelopmental disorder characterized by the association of central nervous system abnormalities and nephrotic syndrome. Galloway-Mowat syndrome type 8, caused by variants in the NUP133 gene, is exceptionally rare and exhibits considerable phenotypic heterogeneity. While developmental delay, microcephaly, and renal involvement are recognized manifestations, congenital heart disease has rarely been reported. We describe case of a child with developmental delay, dysmorphic features, and ventricular septal defect without nephrotic syndrome, caused by novel missense mutations of NUP133 gene, thereby expanding the phenotypic spectrum of disease.
Case Report: A 32-month-old female child born to non-consanguineous parents presented with severe growth failure, global developmental delay, microcephaly, dysmorphic facial features, cleft palate, and syndactyly. She had previously undergone surgical correction of a large peri-membranous ventricular septal defect with atrial septal defect. Brain magnetic resonance imaging revealed cortical atrophy with delayed myelination, while renal evaluation showed no proteinuria or evidence of nephrotic syndrome. Whole genome sequencing identified two rare heterozygous NUP133 missense variants [c.2134A>G (p.Arg712Gly) and c.2228G>T (p.Arg743Leu)], both classified as variants of uncertain significance. The overall clinical and genetic findings were suggestive of Galloway-Mowat syndrome type 8.
Conclusion: This case expands the phenotypic spectrum of Galloway-Mowat syndrome by demonstrating developmental delay, microcephaly, dysmorphic features, cortical atrophy, and ventricular septal defect in the absence of nephrotic syndrome. It highlights the clinical heterogeneity of NUP133 associated disease and emphasizes the role of genomic testing in the diagnosis of rare neurodevelopmental disorders with atypical presentation.