What is Birt-Hogg-Dube Syndrome?
Birt-Hogg-Dube syndrome (BHDS) is a genetic skin disorder that typically starts showing symptoms around a person’s 30s. People with this syndrome tend to have numerous small, non-cancerous skin growths like fibrofolliculomas, trichodiscomas, and acrochordons. In simple language, those are skin bumps that form around hair follicles or in other areas. But more than this, people with BHDS are at an increased risk of kidney cancer, developing lung cysts (small, fluid-filled sacs in the lungs), and experiencing collapsed lungs, which can occur spontaneously without a clear cause.
What Causes Birt-Hogg-Dube Syndrome?
Appendicitis is caused by something blocking the appendix (a small organ attached to the large intestine), leading to inflammation or swelling. This blockage may be due to different reasons, like hardened stool particles, growths in the appendix, worm infections, or the swelling of tissue in the appendix. The specific reasons for these blockages can differ based on age, making it important to consider the patient’s age when diagnosing and treating appendicitis.
The appendix naturally contains certain types of bacteria, including Escherichia coli and Bacteroides spp. When the appendix is blocked, these bacteria can multiply too rapidly, causing it to become inflamed and potentially leading to an abscess (a painful, pus-filled area).
In children, appendicitis often occurs due to the overgrowth of a type of tissue called lymphoid tissue in the appendix. This leads to inflammation and poor blood flow to the area. This situation increases the risk of the appendix rupturing (bursting), leading to an abscess and the possibility of an infection spreading throughout the abdomen. Sometimes, this overgrowth of lymphoid tissue is mistakenly identified as one of the other causes of appendicitis.
In adults, appendicitis can happen due to a variety of reasons, including infections, hardened fecal matter, or tumors (abnormal growth of tissue) in the appendix.
Risk Factors and Frequency for Birt-Hogg-Dube Syndrome
Birt-Hogg-Dube syndrome is an uncommon condition that affects both men and women. Most often, people first experience symptoms when they are young adults.
Signs and Symptoms of Birt-Hogg-Dube Syndrome
Birt-Hogg-Dube Syndrome (BHDS) is a condition that presents itself with many small, waxy, dome-like white bumps, typically 2 to 4 millimeters in size. These are often found on the nose and cheeks but can also appear on the ears, neck, and body. Some people may only have a few, whilst others could have hundreds.
These bumps are safe and non-cancerous growths known as trichodiscomas or fibrofolliculomas. Experts still debate if these two types of growths, along with another kind called acrochordons or skin tags, are different expressions of the same type of lesion. They can be hard to tell apart when just looking at them, and even when examining them under a microscope, sometimes the specific features of fibrofolliculomas only come into view when the sample is cut horizontally. In BHDS, skin tags might be a form of fibrofolliculomas, but this is still a point of contention.
BHDS can also cause other skin changes and internal symptoms:
- Soft bumps on the lips, gums, and inside the cheeks
- Connective tissue nevi
- Lipomas
- Angiolipomas
- Facial angiofibromas
- Medullary thyroid cancer
- Thyroid adenomas
- Parotid oncocytomas (a type of salivary gland tumor)
- Basal lung cysts
- Parathyroid adenomas
In the past, it was thought that BHDS could increase the risk of developing colon polyps and other tumors, but recent studies have found no such link. Because BHDS can manifest in so many different ways, it’s often not diagnosed until more severe symptoms show up, such as kidney cancer or a collapsed lung. Both of these conditions can also happen on their own, without any genetic cause, so doctors may not suspect BHDS at first.
Testing for Birt-Hogg-Dube Syndrome
In 2009, Menko and his team laid out a set of criteria for diagnosing Birt-Hogg-Dube syndrome (BHDS). The patient needs to meet either one major criterion or two minor criteria to be diagnosed with this condition (Table 1).
The major criteria include either having at least five particular skin bumps, known as fibrofolliculomas or trichodiscomas, confirmed by skin tissue examination, and developing in adulthood or having a proven harmful mutation in the FLCN gene. However, in up to 40% of patients who test negative for the FLCN gene mutation, the diagnosis of BHDS can still be made if other criteria are met.
The minor criteria cover having multiple lung cysts that are located on both lungs and towards the bottom, developing kidney cancer before turning 50 years old or having it spread to both kidneys or a mix of chromophobe and oncocytic histology (types of kidney cancers). The last minor criterion would be having a close family member, such as a parent or sibling, diagnosed with BHDS.
One unique feature of BHDS is sometimes seeing kidney cancers that are a mix of chromophobe and oncocytoma. These types of cancer together in the same patient are fairly unique to BHDS.
The tools used to check for symptoms related to BHDS include a chest X-ray and high-resolution chest computed tomography (CT) scan, which can be used to look for lung cysts. Doctors might also use an abdominal CT scan or a magnetic resonance imaging (MRI) scan to examine the kidneys.
Treatment Options for Birt-Hogg-Dube Syndrome
Birt-Hogg-Dube syndrome, or BHDS, is associated with a range of skin abnormalties. Several treatments have been tried to deal with these abnormalties, including electrocautery, curettage, and laser ablation, which are techniques to remove or destroy the lesions. However, these methods often result in the lesions returning later on.
There’s been some research into using a medication called rapamycin that has been found to decrease kidney damage and increase survival rates in animal models with BHDS. However, evidence from human trials has shown no significant improvements when using rapamycin as a topical application for certain skin growths associated with BHDS.
People living with BHDS are also at a higher risk of kidney tumors, usually around the age of 50. To manage this, doctors recommend that kidney checks should begin from the age of 20. Different experts suggest different types of scans, including MRI, ultrasound, or CT scans at varying frequencies to monitor the kidneys.
In addition to kidney tumors, folks with BHDS are also susceptible to pneumothoraces, a condition where air collects in the area between the lung and the chest wall. This condition affects about a quarter of patients in their later years. Regular chest scans are recommended to monitor this as well. Despite these risks, there is currently no evidence suggesting that air travel can worsen the condition. It’s very important, nonetheless, for patients to quit smoking, as it can trigger pneumothoraces.
Lastly, regular full-body skin checks are crucial for these patients to look for any suspicious changes in pigmentation or growths on the skin. This monitoring is particularly important as some research suggests there may be a connection between skin cancer, specifically malignant melanoma, and BHDS.
What else can Birt-Hogg-Dube Syndrome be?
Flesh-colored bumps on the head and neck can be found in several different conditions. For example, one disorder is called Cowden syndrome, where a person has many skin growths, called trichilemmomas, on the face, neck, and ears. This syndrome is passed down through families, and people with this condition might also have skin changes inside the mouth, rough-textured lips, skin growths on the hands and feet, and an enlarged heart.
Another condition to consider is Hornstein-Knickenberg syndrome. In this disorder, also passed down through families, the person has small skin growths or tiny fibromas around the hair follicles. What sets this syndrome apart is a higher risk of growths in the colon.
On a similar note, diseases like tuberous sclerosis and Brooke-Spiegler syndrome can also show up as flesh-colored bumps. Tuberous sclerosis, caused by a faulty gene, can lead to skin growths called angiofibromas and collagenomas, white patches on the skin, and small fibroid growths around the nails.
Brooke-Spiegler syndrome, due to a different faulty gene, leads to the appearance of spiradenomas, trichoepitheliomas, and cylindromas. Trichoepitheliomas are firm, flesh-colored lumps that mainly crop up on the creases around the nostrils, nose, upper lip, and head.
Basaloid follicular hamartoma syndrome is another possible condition, which also shows up as flesh-colored bumps. However, these bumps often turn pinkish over time and form a raised, rough area on the skin. To find out what’s causing the bumps, doctors often will take a sample to examine under a microscope, and they’ll discuss any other symptoms the patient might have, their past health problems, and their family’s health history.
You should know that some conditions might lead to lung cysts and pneumothorax, like lymphangioleiomyomatosis, emphysema, and pulmonary Langerhans cell histiocytosis. Kidney tumors might be seen in syndromes such as von Hippel-Lindau syndrome or hereditary leiomyomatosis. However, most cases of lung and kidney issues occur without a clear genetic link.
