Expanding the Phenotypic Spectrum of NUP133 Associated Galloway-Mowat Syndrome: A Case Report with Developmental delay, Dysmorphism, and Ventricular Septal Defect without Nephrotic Syndrome.

Abstract

Background: Galloway-Mowat syndrome (GAMOS) is a rare neurodevelopmental disorder characterized by the association of central nervous system abnormalities and nephrotic syndrome. GAMOS type 8 (GAMOS8), 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 a child with developmental delay, dysmorphic features, and ventricular septal defect (VSD) without nephrotic syndrome, thereby expanding the phenotypic spectrum of NUP133 associated disease. Case summary: 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 VSD with atrial septal defect. Brain MRI 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 GAMOS8. Conclusion: This case expands the phenotypic spectrum of GAMOS8 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.