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Abstract: SA-PO553

Refractory Focal Segmental Glomerulosclerosis: A Presentation of Alport Syndrome

Session Information

  • Genetic Diseases: Diagnosis
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

  • 1102 Genetic Diseases of the Kidneys: Non-Cystic


  • Alrejjal, Kenan Mohd Rashad Said, CLS Health, Houston, Texas, United States
  • Abdullatif, Umayma, CLS Health, Houston, Texas, United States
  • Beretich, Lauren, Natera, Inc., Austin, Texas, United States
  • Bloom, Michelle, Natera, Inc., Austin, Texas, United States
  • Punj, Sumit, Natera, Inc., Austin, Texas, United States
  • Abdellatif, Abdul A., Baylor College of Medicine, Houston, Texas, United States

Alport syndrome (AS) is a genetic condition caused by variants in the COL4A3/4/5 genes. While classically characterized by progressive kidney disease, hearing loss, and ocular abnormalities, the use of genetic testing has expanded our understanding of the AS phenotype. Individuals with AS, notably autosomal dominant, are also known to present with benign hematuria, thin basement membrane nephropathy, and focal segmental glomerulosclerosis (FSGS) with or without extrarenal manifestations. The purpose of this study was to describe a case of FSGS refractory to multiple immunosuppressive regimens that was later diagnosed as AS.

Case Description

A 38-year-old Caucasian female with a history of biopsy-proven FSGS at 19 years of age with severe nephrotic syndrome. The patient was refractory to multiple lines of immunosuppressive therapy. Furthermore, an eye exam revealed keratoconus. These findings along with her family history of kidney conditions prompted genetic testing with a panel of 385 genes (the RenasightTM test) to help understand the etiology of her renal presentation and to determine further management.

Genetic testing identified a heterozygous, likely pathogenic variant (c.1565G>A, p.Trp522*) in COL4A4, associated with AS. This variant is predicted to result in a stop-gain in exon 22 of the COL4A4 gene. While c.1565G>A (p.Trp522*) is private to this family, other putative loss-of-function variants downstream of this position have been reported to be pathogenic. The patient’s 10 year old daughter was also found to have hematuria, and was subsequently found to have the familial variant in COL4A4.


This case exemplifies the variable presentation of AS and the value of genetic testing for the proband and their family. The patient’s condition was reclassified, enabling appropriate intervention, treatment resistance assessment and family testing. In addition, the patient’s daughter received an early diagnosis, guiding future treatment plans and options while avoiding unnecessary risk exposure. The family’s genetic diagnosis allowed for accurate genetic risk assessment and may increase access to targeted treatments or clinical trials in the future. Ultimately, genetic testing should be considered for individuals with FSGS, given the association with AS and other genetic conditions.