Hepatocyte Nuclear Factor-1 Beta (HNF1B) is a gene involved in the development of several organs including the kidneys, pancreas, reproductive tract and liver. People with a change in the HNF1B gene can have a variety of problems associated with these organs. This is sometimes called the Renal Cysts and Diabetes (RCAD) syndrome because these are the most common features.
How does this affect the kidneys?
The kidney is the most common organ to be affected. The most common feature is cysts (fluid filled swellings) in the kidneys. These are usually seen when an ultrasound scan is performed to look at the size, shape and structure of the kidneys.
Other findings may include small kidneys or the presence of only one kidney, which may be of normal or abnormal shape. Sometimes these changes can be seen before birth on an antenatal scan.
These abnormalities have a variable effect on how well the kidneys work. Some people are only mildly affected and although they have cysts, their kidneys work normally. Other people may be more severely affected and their kidneys may fail. In very rare cases an affected foetus may not survive.
What about HNF1B and diabetes?
Diabetes is the second most common problem. However not all people with a change in HNF1B will develop diabetes. Diabetes can develop at any age but particularly in adolescence or young adulthood. Sometimes it appears for the first time in pregnancy.
Diabetes is a problem with the pancreas, the organ that makes insulin. Some people with changes in HNF1B have a pancreas that is smaller than usual. This can be picked up on different types of scans (CT, MRI and sometimes ultrasound). (Visit the Clinicians page for more information on diabetes testing). The pancreas, which is in the abdomen, produces enzymes to digest food. If people cannot make enough of these enzymes, it can cause loose stools and weight loss.
What other abnormalities can be caused by changes in HNF1B?
Women can have abnormalities of the reproductive tract. This usually means that the uterus is a different shape or there may be a double uterus. These problems may be picked up on an ultrasound scan. Some of these abnormalities may reduce the ability to conceive or have a successful pregnancy. However it is possible for a woman with a uterine abnormality caused by a change in the HNF1B gene to have a successful pregnancy.
Some people with changes in the HNF1B gene have mild abnormalities of the liver. These are picked up either on blood tests of liver function or on an ultrasound scan. However significant liver disease is very unlikely.
Some people, including women and young adults, are prone to attacks of gout and high levels of uric acid in the blood. This form of gout is different from the common condition affecting older people, usually men, that is associated with high blood pressure, obesity and diabetes.
Some people have low levels of magnesium. While this may cause cramp, it is usually symptomless.
People who are missing one copy of the HNF1B gene may have a neurodevelopmental disorder such as autism or autism spectrum disorder.
For many people with kidney abnormalities, no treatment is needed. It is important however that renal function, blood sugar and blood pressure are all checked regularly, as indicated by the patient’s clinician.
If kidney function decreases, treatment will depend upon the Stage of Chronic Kidney Disease (CKD). Artificial kidney treatment (dialysis or transplantation) would only be required if function is very low (CKD 4-5).
Diabetes caused by changes in HNF1B is usually treated with insulin injections. However it may be possible to use diet modification or anti-diabetic tablets initially.
Women intending to become pregnant may wish to seek obstetric advice to identify any future risks to their own health or that of their baby. They may also at this time request clinical genetic advice (see How the disease works below).
Patients should have their level of uric acid measured from time to time, as indicated by their clinician. This should give advance warning of the risk of developing gout. If the risk is high, or if they have already developed symptoms, patients will be treated with an oral medication to reduce the build up of uric acid.
If patients develop cramp that is caused by low magnesium levels in the blood, oral magnesium supplements may help.
The first HNF1B patient information day was held in September 2012. Presentations are available here. The second patient information day took place on Saturday 27th February 2016 at the Nowgen Centre, 29 Grafton Street, Manchester. Presentations are available here.
Hepatocyte Nuclear Factor1Beta (HNF1B) acts as a switch to turn other genes on and off. It is involved in the early development of several organs, including the kidneys, pancreas, reproductive tract and liver.
If the development is abnormal, this affects the structure of the organs concerned. For example, irregular growth and development of the microscopic tubules in the kidney can result in the formation of cysts. Likewise, if the pancreas doesn’t develop normally there may not be enough of the insulin-producing beta cells to provide normal regulation of blood sugar. Even where an organ is structurally abnormal, it may still provide adequate function for health for a considerable time.
If you have renal cysts and diabetes it is worth undergoing genetic testing to see if there are disease-causing changes in HNF1B.
There are two ways in which the abnormality can occur. An individual may be the first person in a family to have the mutation (new mutation). Alternatively it may have been passed down from one or other parent. Everyone has two copies of HNF1B, one inherited from each parent. Because the disease is so variable, even within the same family, a parent may carry and pass on the gene without showing signs of illness themselves. The reason for this wide variation in the severity of the disease is currently unknown.
Sometimes when a person has been correctly diagnosed, and the gene change confirmed, the disease can be recognised in other family members for the first time. For example, if other members of a patient’s family have kidney abnormalities such as cysts or diabetes it is quite likely that they also carry the same change in the HNF1B gene.
Anyone who has a change in the HNF1B gene has a 50% chance of passing this on to their child. Professional genetic advice may be obtained from a regional genetic service, to which you or a family can be referred by your hospital consultant or GP.
The HNF1B Rare Disease Group is currently setting up an on-line registry for patients with this condition. The aim is to find new and improved treatments and to empower patients. A first step will be to compare the symptoms and genetic markers of HNF1B. The database may also be used to find suitable people to take part in future research trials to monitor the effectiveness of new treatments and medicines. The data will be anonymous and confidential. Participation in the registry is entirely voluntary.
If you are interested in finding out more about the registry please visit the HNF1B RDG page.