Hepatocyte nuclear factor 1ß (HNF1ß)–associated disease

The signs and symptoms of HNFB1-associated disease can vary from person to person. Kidney abnormalities associated with HNF1B-associated disease can occur at any age, from infancy to adulthood.^[1][5] The kidney abnormalities seen with HNFB1-associated disease can include:

• Small, fluid-filled sacs in the kidney (renal cysts) 
• Small, abnormally shaped kidney
• An absent kidney
• Abnormalities of internal kidney structure
• Kidney failure (end-stage renal disease)

Additional signs and symptoms can include ^[2]:
• Diabetes before age 25 (but can occur at any age)
• Underdeveloped pancreas and abnormal pancreatic function
• High levels of liver enzymes suggesting abnormal liver function 
• Abnormalities of the male and female sex organs  (genitals)
• Over-active parathyroid gland causing too much calcium in the body
• Low magnesium levels that can cause muscle weakness and spasms
• Gout at a young age
• Possible increased risk for kidney cancer

The HNF1B  gene is one of many genes found on chromosome 17. In conditions that involve missing pieces of chromosome 17, the HNF1B gene might be missing along with other genes, resulting in a loss of the HNF1B protein and other proteins. Missing pieces of chromosome 17 that involve the HNF1B gene, along with other missing genes, have been associated with epilepsy, autism spectrum disorder and developmental delay.^[2][3]

HNF1B-associated disease is caused by a mistake (mutation) in the HNF1B gene, which is responsible for making a protein that is involved in the early development of many different organs within the body.^[1] Mutations in the HNF1B gene can cause abnormal development of the kidneys, pancreas, parathyroid gland and liver.^[4]

HNF1B-associated disease can be inherited in an autosomal dominant pattern.^[1][2] All individuals inherit two copies of each gene. In autosomal dominant conditions, having a mutation in just one copy of the associated [HNF1B] gene causes the person to have the disease. Many people who have HNF1B-associated disease are born with this condition due to a new genetic mutation (de novo) and do not have a history of this condition in their family. There is nothing either parent can do, before or during pregnancy, to cause a child to have this.

Each child of an individual with an autosomal dominant condition has a 50% or 1 in 2 chance of inheriting the HNF1B mutation and HNF1B-associated disease. Children who inherit the HNF1B mutation will have HNF1B-associated disease, although they could be more or less severely affected than their parent.

The diagnosis of HNF1B-associated disease is made based on the symptoms and genetic testing.  A family history of kidney disease, diabetes or gout at an early age may be helpful, but many people with HNF1B-associated disease are the first person in their family to have the diagnosis. Laboratory testing may include blood tests to monitor kidney function, check for diabetes, and measure magnesium and calcium.^[5]

There is no specific treatment for HNF1B-associated disease. Treatment is based on individual symptoms. Kidney disease can be managed with dialysis. Kidney transplant is an option for treating kidney failure.^[5] Some people with this condition may also benefit from a pancreas transplant. Gout can be prevented with certain medications (allopurinol  or febuxostat) or managed with nonsteroidal anti-inflammatories.^[5] Diabetes can be managed with medication and diet.

The long-term outlook for people with HNF1B-associated disease varies based on the severity of the symptoms.^[2] Early diagnosis may be helpful for children with this condition.^[5]

The exact prevalence of HNF1B-associated disease is difficult to estimate.^[1] Renal cysts and diabetes may occur is about 1-9/1,000,000 people.^[3]