Abstract: FR-PO0138
A Case Report of Secondary FSGS Associated with Dual Genetic Variants in NIPBL and COL4A4
Session Information
- Hereditary Glomerular and Tubulointerstitial Kidney Diseases
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Authors
- Shah, Syed Zia-ur-Rehman, Division of Nephrology, Department of Medicine, Medical College of Georgia at University of Augusta, Augusta, Georgia, United States
- James, Leighton R., Division of Nephrology, Department of Medicine, Medical College of Georgia at University of Augusta, Augusta, Georgia, United States
- Mulloy, Laura L., Division of Nephrology, Department of Medicine, Medical College of Georgia at University of Augusta, Augusta, Georgia, United States
Introduction
Focal segmental glomerulosclerosis (FSGS) is a histopathologic lesion that may arise from primary podocytopathy or secondary adaptive and genetic mechanisms. While monogenetic abnormalities may account for many cases of FSGS, the spectrum of mutations causing FSGS is still being defined. We report on a patient with biopsy-proven FSGS and complex genotypic findings.
Case Description
Our patient is a 55-year-old woman referred for chronic kidney disease (stage 3b, eGFR 43 ml/min/m2) and proteinuria (spot urine albumin-creatinine ratio 1371 mg/g). She had a history of recurrent childhood urinary tract infections, hearing impairment, short stature, macular dystrophy, and longstanding hypertension.
Serologic tests (including ANA, anti-Smith, anti-PLA2R) and complement levels were negative. SPEP, UPEP, FLC ratio, and immunofixation were unremarkable and ultrasound revealed normal-sized kidneys. Kidney biopsy demonstrated FSGS with severe arteriolar hyalinosis suggestive of secondary disease. Genetic testing revealed a heterozygous pathogenic variant in the NIPBL gene associated with Cornelia de Lange syndrome (CdLS) type 1 and a heterozygous COL4A4 variant associated with autosomal dominant Alport spectrum disease
Discussion
CdLS renal manifestation includes vesicoureteral reflux, renal dysplasia, hydronephrosis, and recurrent urinary tract infections. Separately, pathogenic variants in COL4A4 are associated with Alport spectrum disease, which may manifest with hematuria, CKD, hearing impairment, ocular abnormalities, and progressive proteinuria. Heterozygous COL4A4 variants may also present as thin basement membrane nephropathy with variable penetrance. In this patient, coexistence of multisystem developmental abnormalities (caused by mutant NIPBL leading to CdLS phenotype), ocular disease, bilateral hearing loss and CKD support a complex genetically mediated nephropathy contributing to secondary FSGS