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Birt-Hogg-Dubé Syndrome

What is Birt-Hogg-Dubé Syndrome?

Birt-Hogg-Dubé Syndrome is a complex and rare genetic skin disease that characteristically leads to the development of skin papules. These papules generally occur on the head, upper torso and the face. The skin papules often take the form of tumors but are mostly noncancerous in their nature and appear at the hair follicles. They are called fibrofolliculomas. The condition of Birt-Hogg-Dubé syndrome can also lead to pneumothorax which is a condition of repeated failure of the lungs or development of cysts in the lungs. It can also lead to kidney neoplasia. Birt-Hogg-Dubé syndrome can cause mutation of the FLCN gene which can happen due to an autosomal trait.

What is Birt-Hogg-Dubé Syndrome?

Signs and Symptoms of Birt-Hogg-Dubé Syndrome

There is not much of standard parity when we talk of the symptoms that are common in this condition. The symptoms of Birt-Hogg-Dubé Syndrome can widely vary from person to person. However, even then it has been seen that there are some very common symptoms.(1) They are pulmonary or lung cysts, the formation of skin lesions, a repeated threat of lung collapse and renal neoplasia. Almost 85% of the patients suffering from Birt-Hogg-Dubé Syndrome are seen to develop skin papules. However, there can also be instances of patients developing lung cysts and kidney neoplasia without the formation of skin lesions.(2)

Skin papules that are also referred to as fibrofolliculomas although commonly occurs on the necks, face and the scalp, it can also be found on the regions of oral mucosa and ear lobes. The symptoms can vary widely in patients even in those from the same family. This is because the symptoms will depend on the nature of the mutation of the genes. For example, the number of skin lesions can vary in a dramatic manner. Some patients are seen to have just a few of them whereas others have a large number of them.

People suffering from Birt-Hogg-Dubé syndrome can also develop multiple lung cysts that can affect both the lungs. This has been seen in nearly 80% of the people who are affected by this disease. In most cases, these cysts do not hamper the normal functioning of the lungs. Normally one-third of Birt-Hogg-Dubé Syndrome patients face the condition of the collapse of the lungs. This happens when air gets trapped in the surrounding region of the lungs. It can happen in younger people and has been reported in children around the age of 7 to 16 years. A child who has been affected by FLCN mutation has 50% greater chances of lung collapse as compared to their siblings who do not have this mutation.(2)

Nearly 30% of patients with Birt-Hogg-Dube Syndrome develop renal neoplasms. These growths are generally slow and can develop over a span of many years. It is around the age of 45 – 50 years that the symptoms become potent enough to get diagnosed. People who have been affected by Birt-Hogg-Dubé syndrome have a greater risk of developing cancerous kidney growths as compared to other people.

Diagnosis of Birt-Hogg-Dubé Syndrome

The condition of Birt Hogg Dube Syndrome is often diagnosed on the basis of clinical findings. However, this is a condition that can also be diagnosed on the basis of molecular genetic testing which is done for finding out the extent and the nature of mutation of the FLCN gene.

Clinical Trial of Birt-Hogg-Dubé Syndrome

One of the main factors that help in the diagnosis of the condition is the presence of the cutaneous manifestations that are common in Birt-Hogg-Dubé syndrome. These growths were initially described as the fibrofolliculomas or also as abnormal growth in the reign of the hair follicle, trichodiscomas which occurs in the region of the hair follicle periphery and is common in the area of the face. The acrochordons or skin tags are also a common symptom of Birt-Hogg-Dubé Syndrome The first symptoms of cutaneous manifestations can be confirmed through the process of histology. Often it has been seen that nearly 89% of people who has Birt-Hogg-Dubé syndrome has multiple cysts in both their lungs. Nearly 24% of these patients must have experienced some episodes of pneumothorax. These cysts and their presence can be made out with the help of CT scan of the chest. Renal tumors and its other types are also discerned with the help of pathological subtypes. Initially the diagnosis was based on the cutaneous findings; however, in recent times other procedures of diagnosis that relates to the pulmonary readings and the renal readings are also brought to use. The skin lesions are also tested in order to find out about the condition. The nature of these skin lesions can be found out on the basis of genetic tests of FLCN mutation.

Genetic Testing for Birt-Hogg-Dubé Syndrome

Genetic testing is also done so that a diagnosis of the condition can be made. This is also known as sequencing that is used in the context of a minimum of 88% of patients. People who do not have symptoms can be diagnosed with the help of the clinical test that shows the mutation of genes. At this stage, certain tests in the exonic regions of the body are also made that gives more direct indications at the existence of the condition. Often further genetic testing is prescribed so that the findings of the clinical diagnosis can be further confirmed. This is one of the most common practices that are being followed by the doctors so that they can be doubly sure of the situation.

Through the genetic testing, other family members who have not shown the symptoms of Birt-Hogg-Dubé Syndrome but might be at risk of developing the condition in the future can also be discerned. This will help in the further process of management of the condition.

Differential Diagnosis for Birt-Hogg-Dubé Syndrome

Finding out the condition of Birt-Hogg-Dubé syndrome just on the basis of clinical testing is not possible. This is because the symptoms could be from other health problems and not this condition in particular. Renal tumors that are common in this condition also occur in the context of von Hippel-Lindau disease, hereditary papillary renal cancer, and many other renal related problems. The differentiation can be done on the basis of the turner histology tests. There are other conditions like Marfan syndrome, TSC, cystic fibrosis and lot many other conditions where the symptoms could be similar to those of Birt-Hogg-Dubé syndrome. A proper diagnosis is made only after a detailed analysis of patient history.

Causes of Birt-Hogg-Dubé Syndrome

The Birt-Hogg-Dubé Syndrome is an inherited condition that can affect people with an inherited mutated gene. Such genetic disorder is dependent on the combination or the single genes that could be inherited either from both or any single parent. Such gene could also occur as a singular and independent mutation where none of the parents might have the trait in them. Each pregnancy has a 50% chance where the infant can inherit the mutated gene. Both male and female children are at the same risk levels.(1)

In certain cases, it is seen that a spontaneous genetic mutation occurs at the sperm or the egg cell itself. This is a condition where the child does not really inherit the mutated gene from their parents.

The Birt-Hogg-Dubé syndrome is caused due to a mutation of the FLCN gene. The FLCN gene contains follicle which is a protein. The precise function of this protein is not known yet. However, this protein helps in the growth of the cells. The FLCN gene is a tumor suppressor gene that helps to check the growth of the cells and repairs the damages done for the DNA cells. Mutation of this gene can cause a rise of cancerous tumors.

Epidemiology of Birt-Hogg-Dubé Syndrome

This is a highly debatable issue. It has been stated that Birt-Hogg-Dubé Syndrome can arise for people who might have inherited the mutated genes from their parents. This means that children or infants who have parents with affected genes might get this syndrome. However, it is also seen that often patients who have this syndrome have a perfectly healthy set of parents. It could be due to the fact that their parents have been asymptomatic or did not have a problem at all. In the latter case, it has been seen that patients have developed the problem on their own as the FLCN gene mutations have happened for them alone and have not been passed to them by their parents.

Treatment of Birt-Hogg-Dubé Syndrome

Birt-Hogg-Dubé syndrome is a condition that leads to a number of problematic situations as it has a number of adverse effects on the human body. The kind of treatment that is to be given to Birt-Hogg-Dubé Syndrome patient will depend on the nature and the extent of the damage that has been rendered to the patient. In many situations where a tumor needs to be removed, different methods are applied for the task such as skin resurfacing, excision, laser ablation, shave and curettage. However, none of this happens to be a permanent solution as such tumors can reappear. Often if this tumor happens in the kidneys, a preventive measure of keeping a track and observation of the tumor is followed by the doctors.(2) In the process of doing so, MRI is preferred over CT scan as it has minimum radiation. To treat the renal tumor, the method of partial nephrectomy is done so that just a part of the kidney that has the tumor is removed instead of the whole kidney.


A lot of research needs to be made into the domain so that healthcare professionals can understand the exact nature and the true causes of the problem. However, it has been understood that the role of human genes plays a very important role here. The human gene is a highly dynamic and also complex thing. The nature and the behavior of these genes are still not completely understood. It has been agreed that one can inherit them from the parents and the chromosomes from the parents can affect the genes to a great extent. However, mutation of these genes is also a very important part of the study and has not been understood till date. There could be various factors that actually affect its working. As on today, the management revolves around symptomatic management.


Pramod Kerkar, M.D., FFARCSI, DA
Pramod Kerkar, M.D., FFARCSI, DA
Written, Edited or Reviewed By: Pramod Kerkar, M.D., FFARCSI, DA Pain Assist Inc. This article does not provide medical advice. See disclaimer
Last Modified On:October 10, 2019

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