Dr Julien Nithianandan1, Dr Patrick Cooney1, Anna Leaver2, Dr Po Yee Mia Leung3,4
1Department of Renal Medicine, Bendigo Health, , Australia, 2Clinical Genetics, Austin Health, , Australia, 3Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, , Australia, 4Department of Nephrology, Austin Health, , Australia
Biography:
Julien is a nephrology advanced trainee who has worked in Victoria and the Northern Territory. His interests include chronic disease management, lupus nephritis, and the health of Aboriginal and Torres Strait Islander peoples.
Background:
Nail-Patella Syndrome (NPS) is a rare autosomal dominant disorder characterised by changes in the nails, elbows, patellae, and iliac horns. 85% of cases are linked to mutations in the LMX1B gene, essential for podocyte structure and function. 30-40% of affected individuals develop kidney involvement.
Case Report:
A female in her 50s presented for perioperative assessment prior to elbow debridement for osteoarthritis. She had no family history of kidney disease. Blood pressure was 120/70mmHg and there was no peripheral oedema. Investigations showed normal renal function, nephrotic-range proteinuria and microscopic haematuria. Renal imaging was normal. Renal biopsy showed focal segmental glomerulosclerosis (FSGS) with electron microscopy demonstrating 50% podocyte foot process effacement, no deposits, and focal glomerular basement membrane thickening. No secondary causes of FSGS were apparent.
Genomic testing using whole exome sequencing was conducted and the PanelApp Australia Kidneyome SuperPanel gene list was analysed. This revealed a class IV (likely pathogenic) LMX1B variant, consistent with a genetic diagnosis of NPS.
Targeted assessment revealed phenotypic features consistent with NPS including bilateral elbow osteoarthritis and previous left patella dislocation requiring operative management. She had pathognomonic nail changes including dystrophic and split thumbnail, and triangular lacunae. Re-review of the renal biopsy did not show classic “holes” in the glomerular basement membrane.
She was commenced on supportive management and counselled on annual screening for glaucoma (associated with NPS). A family letter was provided for consideration of cascade testing.
Conclusion:
Clinicians should be cognisant of FSGS as a manifestation of syndromic disorders, of which NPS is a rare example with significant familial implications. Genomic testing is an increasingly important tool in the evaluation of FSGS, allowing for precise diagnosis, consideration of immunosuppression utility, and prognostication.