Hepatic phenotypes of HNF1B gene mutations: a case of neonatal cholestasis requiring portoenterostomy and literature review

World J Gastroenterol. 2015 Feb 28;21(8):2550-7. doi: 10.3748/wjg.v21.i8.2550.


Hepatocyte nuclear factor 1-β (HNF1B) defects cause renal cysts and diabetes syndrome (RCAD), or HNF1B-maturity-onset diabetes of the young. However, the hepatic phenotype of HNF1B variants is not well studied. We present a female neonate born small for her gestational age [birth weight 2360 g; -2.02 standard deviations (SD) and birth length 45 cm; -2.40 SD at the 38(th) gestational week]. She developed neonatal cholestasis due to biliary atresia and required surgical intervention (portoenterostomy) when 32-d old. Following the operation, icterus resolved, but laboratory signs of liver dysfunction persisted. She had hyperechogenic kidneys prenatally with bilateral renal cysts and pancreatic hypoplasia postnatally that led to the diagnosis of an HNF1B deletion. This represents the most severe hepatic phenotype of an HNF1B variant recognized thus far. A review of 12 published cases with hepatic phenotypes of HNF1B defects allowed us to distinguish three severity levels, ranging from neonatal cholestasis through adult-onset cholestasis to non-cholestatic liver impairment, all of these are associated with congenital renal cysts and mostly with diabetes later in life. We conclude that to detect HNF1B variants, neonates with cholestasis should be checked for the presence of renal cysts, with special focus on those who are born small for their gestational age. Additionally, patients with diabetes and renal cysts at any age who develop cholestasis and/or exocrine pancreatic insufficiency should be tested for HNF1B variants as the true etiological factor of all disease components. Further observations are needed to confirm the potential reversibility of cholestasis in infancy in HNF1B mutation/deletion carriers.

Keywords: Biliary atresia; Hepatocyte nuclear factor 1-β; Maturity-onset diabetes of the young; Portoenterostomy; Renal cysts and diabetes syndrome.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biliary Atresia / complications
  • Biliary Atresia / diagnosis
  • Biliary Atresia / genetics*
  • Birth Weight
  • Central Nervous System Diseases / complications
  • Central Nervous System Diseases / diagnosis
  • Central Nervous System Diseases / genetics*
  • Cholangiopancreatography, Magnetic Resonance
  • Cholestasis / diagnosis
  • Cholestasis / genetics
  • Cholestasis / surgery*
  • DNA Mutational Analysis
  • Dental Enamel / abnormalities*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Hepatocyte Nuclear Factor 1-beta / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Small for Gestational Age
  • Kidney Diseases, Cystic / complications
  • Kidney Diseases, Cystic / diagnosis
  • Kidney Diseases, Cystic / genetics*
  • Mutation*
  • Phenotype
  • Portoenterostomy, Hepatic*
  • Treatment Outcome


  • HNF1B protein, human
  • Hepatocyte Nuclear Factor 1-beta

Supplementary concepts

  • Renal cysts and diabetes syndrome