OLIGONEPHRONIA ASSOCIATED WITH OTHER CONDITIONS: A TWO-CASE SERIES

Oligonephronia is a form of kidney hypoplasia characterized by reduced nephron number, glomerular hypertrophy, and progressive kidney dysfunction. Only a few cases with associated conditions have been reported; we describe two additional cases.

Case 1: A 16-year-old female was born at 37 weeks, weighing 2,710 g, with no significant perinatal or family history. At 5 months, she developed a urinary tract infection and was diagnosed with left-sided vesicoureteral reflux (Grade 1). At 13 years, elevated intraocular pressure revealed proteinuria and reduced kidney function (eGFR 64 mL/min/1.73 m²). Kidney biopsy showed enlarged glomeruli and low glomerular density (1.76/mm², normal 3.5–7.0/mm²), consistent with oligonephronia. At 14 years, she developed hepatic dysfunction that improved with hepatoprotective therapy after excluding infectious, autoimmune, metabolic, and drug-related causes. The combination of oligonephronia, liver dysfunction, kidney hypoplasia, and genital anomalies suggested HNF1β-related disease (diagnostic score: 12; ≥8 indicative). Due to additional features of micrognathia and mild intellectual disability, chromosomal microarray analysis was performed, identifying a 2p15p16.1 microdeletion.Case 2: A 15-year-old girl was born at 24 weeks, weighing 450 g as the first twin of a monozygotic pair. Her family history included type 2 diabetes in her paternal grandfather, father, and younger sister. At 14 years, school screening revealed proteinuria. Further evaluation confirmed proteinuria, hematuria, and glycosuria with normal kidney function. As glycosuria suggested diabetes, she was referred for further evaluation. Kidney biopsy showed glomerular hypertrophy and low glomerular density (1.80/mm²), consistent with oligonephronia and focal segmental glomerulosclerosis (NOS variant). Based on her family history and suspected diabetes, MODY (maturity-onset diabetes of the young) was suspected, but genetic testing identified a novel heterozygous WFS1 variant (NM_006005.3, c.41A>G), confirming Wolfram syndrome.

2p15p16.1 microdeletion syndrome is known to cause facial dysmorphism and intellectual disability, but oligonephronia, liver dysfunction, and genital anomalies have not been described, suggesting a novel phenotype in Case 1. Because she was not preterm, oligonephronia is unlikely to result from prematurity. The high diagnostic score for HNF1β-related disease and its known link to oligonephronia indicate that the phenotype may result from combined genetic effects, including HNF1β involvement.Wolfram syndrome is characterized by diabetes mellitus, visual impairment, diabetes insipidus, sensorineural hearing loss, and urinary tract abnormalities, and follows an autosomal recessive inheritance pattern caused by WFS1 variants. Oligonephronia has not been previously reported in Wolfram syndrome; in Case 2, it was likely related to prematurity. The identified variant was predicted by MutationTaster to be pathogenic. Although heterozygous, her diabetes is considered a manifestation of Wolfram syndrome, consistent with reports of heterozygous individuals presenting with diabetes only.

Oligonephronia with extrarenal manifestations may indicate other genetic disorders, and genetic testing should be performed proactively.