[Liver, kidneys and diabetes: three faces of HNF1B gene deficit]

Area of Science:

• Genetics
• Endocrinology
• Nephrology

Context:

• Renal Cysts and Diabetes Syndrome (RCAD), also known as HNF1B-MODY or MODY5, is a genetic disorder.
• It results from HNF1B gene mutations, leading to a deficient HNF1B transcription factor.
• RCAD presents with a spectrum of clinical manifestations affecting multiple organs.

Purpose:

• To summarize the key features and diagnostic considerations of HNF1B-related disorders.
• To highlight the association between HNF1B mutations and a distinct syndrome involving renal cysts and diabetes mellitus.
• To emphasize the importance of recognizing RCAD in patients with unexplained cystic kidney disease and/or diabetes.

Summary:

• RCAD is characterized by cystic kidney disease, diabetes mellitus (typically developing in the second decade or later), hepatic impairment (cholestatic jaundice), pancreatic atrophy, and congenital anomalies of the genital tract.
• Renal manifestations can lead to chronic renal insufficiency in childhood or young adulthood.
• Supportive findings include hypomagnesemia (up to 70% of patients) and hyperuricemia. Family history may be negative due to de novo mutations.

Impact:

• Facilitates earlier diagnosis and management of RCAD, potentially improving patient outcomes.
• Aids clinicians in identifying patients with HNF1B-related disease, especially those with unexplained cystic kidney disease or diabetes.
• Contributes to a better understanding of the genotype-phenotype correlations in HNF1B-associated conditions.