Atypical renal phenotype with tubular proteinuria and hypercalciuria in siblings with nail-patella syndrome: evidence for a dual genetic diagnosis.
Geneviève Benoit, Philippe M Campeau, Mélissa Fiscaletti et al.
✦ AI-curated · Sources linked
Case in brief
Three brothers had the skeletal features of nail-patella syndrome and carried the same maternally inherited heterozygous LMX1B mutation. Two developed early-onset proteinuria, predominantly low-molecular-weight, with hypercalciuria and eye abnormalities including cataracts and glaucoma; one also had nephrocalcinosis. Further testing found a hemizygous pathogenic OCRL mutation in these two brothers, but not in their brother, who had no renal involvement. The differing renal presentations alongside the genetic findings supported a dual diagnosis in the affected siblings.
What made this case unusual
The renal phenotype—tubular-predominant proteinuria with hypercalciuria—differed from the glomerular proteinuria typically associated with nail-patella syndrome, and the OCRL mutation was present only in the two brothers with renal involvement.
Diagnostic / clinical pearl
When renal findings in a patient with nail-patella syndrome are atypical, reconsider whether a second genetic diagnosis may explain the phenotype; comprehensive genetic testing can help clarify intrafamilial differences.