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Genetic causes of nephrotic syndrome (NS)

Evaluation and management of inherited causes of nephrotic syndrome in pediatric patients

Nail patella syndrome

  • Inheritance: autosomal dominant
    • LMX1B encodes the LMX1B protein
      • Transcription factor that targets genes related to actin cytoskeleton
        • Important for limb, neuronal, eye development
        • Expressed in podocytes and targets podocin and genes of the glomerular basement membrane (GBM)
  • Phenotype:
    • Variable
    • Most have nail/digit findings, limb, pelvic abnormalities
      • Nail hypoplasia/dysplasia (e.g., discoloration, ridging)
      • Triangular lunulae (visible root of nail is triangular instead of crescent shaped)
      • Limb abnormalities:
        • Elbow abnormalities that limit extension, pronation and/or supination
        • Patella abnormalities can include aplasia or hypoplasia which increases knee instability and risk of dislocation
        • Hyperextensibility of the fingers
      • Pelvic abnormalities:
        • Hyperextensibility of the hips
    • ~50% with kidney manifestations
      • Proteinuria is most common
      • May have microscopic hematuria
      • May have accelerated progression of chronic kidney disease
  • Diagnosis:
    • Kidney biopsy not usually indicated
      • Classically demonstrates fibrillar collagen bundles throughout the glomerular basement membrane and mesangium[PMID 28941488]
  • Treatment:
    • Antiproteinuric medication (ACEi/ARB)