What is Thyroid Transcription Factor Related Lung Disease?
Surfactant is important for normal lungs. Thyroid transcription factor (TTF1) is a protein that switches on genes that help make surfactant. Read more about normal surfactant here.
TTF1-related lung disease happens when there is a problem with the TTF1 protein. The surfactant is not made normally. It may build up inside cells in the alveoli. This causes lung inflammation and injury. Children may also have breathing problems because they don’t have enough normal surfactant in their lungs. Their lungs may also not be fully developed.
This is caused by a mutation (mistake) in the thyroid transcription factor 1 gene (NKX2.1). It is an autosomal dominant condition. This means that a child only needs to have one copy of the abnormal gene to show symptoms. The mutation happens randomly in most cases. It is usually not passed on from parents.
Babies and children with TTF1-related disease can have problems breathing and low oxygen levels. They may also have problems with their thyroid or brain function. For this reason, it is sometimes called ‘brain-lung-thyroid disease’.
Diagnosis:
TTF1-related disease is possible when babies or children have trouble breathing and abnormal chest imaging. Several studies may need to be done. These include:
- A chest x-ray may show areas of pneumonia.
- A lung scan (chest CT) may show areas of grayish-white and could look like areas of pneumonia.
- Genetic testing for the NKX2.1 mutation is usually what can tell us the diagnosis. The results of genetic testing will usually take several weeks. Sometimes testing also needs to be done in parents.
- A lung biopsy may be needed if a child is very sick or if a diagnosis is not made through genetic testing.
- In children aged 6 years and older, pulmonary function tests are used to follow changes in lung function.
After diagnosis, testing should also be done to look at the thyroid and brain.
Treatment:
Treatment is to support breathing and nutrition. There is no cure for any of the surfactant disorders. There are several treatments that doctors might recommend.
Children may need oxygen to help keep their oxygen levels normal. They may need positive pressure to help them breathe oxygen in and carbon dioxide out. Children who are very sick with TTF1-related disease may need the intensive care unit for help breathing. Lung transplant may be considered for babies or children with very severe symptoms.
For new babies, artificial surfactant may help with breathing. It is given through a breathing tube. This only helps for a short time and does not treat the problem long-term. Medicines are often used to block the inflammation in the lungs caused by SP-C build-up. These might include steroids (given by mouth or by injection), azithromycin, or hydroxychloroquine. Some children benefit more from these treatments than others. More research is needed to help doctors understand how well these medications work.
Your medical team will help decide which medicines to use and how long to use them.
What does TTF1-Related Disease mean for my child?
TTF1-related disease can cause different levels of illness in children. Different people with exactly the same TTF1 mutation can be affected in different ways. This makes it hard for doctors to predict what life will be like.
Some children only have mild problems and may not be diagnosed until they are several years old. Their symptoms may be well-controlled with medicines and not need oxygen or other breathing support. Children with more severe disease are usually diagnosed very young. They may need oxygen or positive pressure during their whole life. Some patients will need a lung transplant while others will improve as they get older.
Most children with TTF1 lung disease will also have problems with their thyroid and/or brain. Thyroid disease is usually present from birth, and causes the thyroid gland to be underactive. These children don’t make enough thyroid hormone. Without treatment, this can lead to symptoms including feeling cold, feeling extremely tired, poor growth, and having difficulty learning. This can be treated by giving replacement thyroid hormone as a daily medicine. Brain disease usually causes uncontrollable jerky movements of arms, legs, and face. This usually happens later in childhood. Symptoms may be treatable with medicines.
It is important to protect your child’s lungs from infection by making sure they get the recommended vaccines.
What to watch out for:
- If your child is working hard to breathe, talk to a health care provider. If possible. ask to see a lung specialist who is experienced with these conditions.
- Try to prevent infections from common childhood illnesses. Wash your hands often and ask your friends and family to let you know if they are sick before they are around your child.
- Get your child’s vaccines and yearly flu shot.
This information is for Educational Purposes only. It should not be used as a substitute for the medical advice of one’s healthcare provider.
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Author(s): Marie Wright Reviewer(s): Katelyn Krivchenia Version: