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HNF1B-associated disease refers to a multisystem developmental disorder caused by mutations or deletions in the HNF1B gene (Hepatocyte Nuclear Factor 1-beta, formerly called TCF2) on chromosome 17q12.

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• It is the most common known monogenic cause of developmental kidney disease.
• The clinical spectrum is highly variable, ranging from isolated renal cysts to a syndromic phenotype with renal, pancreatic, metabolic, hepatic, and genital involvement.

Genetics & Pathogenesis

• Inheritance: Autosomal dominant (but ~50% are de novo).
• Mechanism: HNF1B encodes a transcription factor critical for nephrogenesis, pancreatic development, liver function, and genital tract formation.
• Mutations/Deletions → defective transcriptional regulation → renal dysplasia, cysts, and systemic manifestations.
• Part of the 17q12 deletion syndrome, where larger deletions also cause neurodevelopmental delay, autism, and epilepsy.

Clinical Features

Renal involvement (most consistent; hallmark)

• Bilateral renal cysts (cortical or medullary, variably sized).
• Hyperechogenic or dysplastic kidneys on antenatal ultrasound.
• Hypoplastic or glomerulocystic kidneys.
• Progressive chronic kidney disease (CKD), often in adolescence/early adulthood.

Endocrine / Metabolic features

• MODY5 (Maturity-Onset Diabetes of the Young type 5):
  • Early-onset, non-obese diabetes, often requiring insulin.
• Hypomagnesemia (renal Mg wasting).
• Hyperuricemia and early-onset gout.