Abbreviated as BHD by Abbreviationfinder.org, the Birt-Hogg-Dube syndrome is an autosomal dominant hereditary disease based on mutations in the FLCN gene. The patients suffer from multiple skin lesions, lung cysts and kidney tumors. Treatment is limited to symptomatic resection and, if necessary, post-treatment of the tumors.
What is Birt-Hogg-Dube Syndrome?
Hereditary diseases are diseases that are caused by mutation or several mutations in one or more genes and that shape genetic dispositions. Some hereditary diseases occur not only in certain inheritance patterns, but also spontaneously. Birt-Hogg-Dube syndrome falls into the group of hereditary diseases.
The disease is also known as chert Knickenberg syndrome or Fibrofollikulomie with Trichodiskomen and Akrochordonen known. The disease is named after its three first descriptions, the Canadian doctors Birt, Dogg and Dube. It is estimated that the prevalence of Birt-Hogg-Dube syndrome is one to nine cases in 1,000,000 people.
In addition to skin lesions, kidney tumors and lung cysts are among the symptoms of the disease. Usually the age of onset is in adulthood. Although the disease was first described in 1977 and only 100 to 400 family cases have been reported since then, the causes of Birt-Hogg-Dube syndrome are now relatively well researched.
An autosomal dominant inheritance pattern is observed for BHD. Family accumulation was documented in more than 100 families. The individual families showed different variants of the syndrome. This observation justifies the suspicion of a clinical picture that is influenced by the family. Various mutations can be considered as the genetic cause of BHD.
For example, some researchers consider mutations in the FLCN gene at gene locus 17p11.2 to be a possible main cause. This gene codes for folliculin within the DNA. The function of this substance is not yet known. According to speculation, however, the largely unexplored protein is part of the mTOR or Mammalian Target-Of-Rapamycin signal chain.
In addition to folliculin, other proteins may be relevant to the syndrome in a relationship with any hamartoma syndromes. At least for the development of symptomatic kidney tumors and the associated changes, however, mutations in the gene locus 17p11.2 seem to make sense.
Symptoms, ailments & signs
Patients with Birt-Hogg-Dube syndrome suffer from skin lesions, lung cysts, and kidney tumors. The kidney tumors can correspond to benign oncocytomas, malignant chromophobic and clear cell and papillary renal cell carcinomas. Mixed kidney tumors are also possible in terms of symptoms.
Fibrofolliculomas with a circumscribed proliferation of the fibroblasts appear on the skin. Accumulations of collagen are observed around the hair follicle. Basaloid cells sometimes extend into the surrounding fibromucinous stroma. Skin lesions such as trichdiscome or acrochordons can also be characteristic. In most cases, the dermatological symptoms of the syndrome do not appear until between the ages of three and four and persist later.
Often the kidney tumors form later than the skin lesions. The lung cysts of the patients show cystic enlargements of the alveolar spaces and can correspond to microscopic foci as well as take on diameters of several millimeters. The cysts appear thin-walled and are equipped with epithelium. The inhalation pressure can tear them and cause pneumothorax.
Diagnosis & course
The diagnosis of Birt-Hogg-Dube syndrome is based on the typical clinical manifestation and the findings of the histology. A family history can also provide initial clues about the syndrome. Molecular genetic mutation detection in the FLCN gene can confirm the diagnosis and rule out differential diagnoses such as multiple papules.
As part of the diagnosis, a more detailed determination of the multiple lesions is carried out. Such epithelial origins are distinguished from changes of mesodermal and mixed origins. The prognosis for patients with Birt-Hogg-Dube syndrome depends primarily on the severity of the severity. The involvement of internal organs is just as crucial in terms of prognosis as the type of kidney tumor.
Patients with Birt-Hogg-Dube syndrome suffer from kidney tumors, lung cysts and multiple skin lesions. The kidney tumors can be both benign and malignant. Papillary renal cell carcinomas and mixed forms limited to the mucous membrane are also possible. The dermatological symptoms appear in the form of skin rashes of varying degrees.
The lung cysts are microscopic to several millimeters in size. They are thin-walled and provided with a surface-covering cell layer. The pressure in the lungs when you breathe can rupture the cysts, causing a build-up of air between your lungs and your chest in the form of a pneumothorax.
Although the causes of this hereditary disease are relatively well understood, it remains unclear what role the genetic defect plays. Therefore, causal therapeutic approaches are not yet available and treatment is symptomatic. The success of the treatment and the prognosis depend on how far the Birt-Hogg-Dube syndrome has progressed.
There is no specific, dermatological treatment for skin rashes. Surgical removal of the affected areas of the house is possible, although there is a high relapse rate. Since the kidney tumors can spread to surrounding organs, a regular check for potentially malignant changes in these areas must be carried out.
The lung cysts also increase the risk of developing lung cancer. The removal of tumors in the kidney is possible depending on the extent of the diseased tissue. Life expectancy depends on the severity of the kidney tumors and the involvement of the internal organs.
When should you go to the doctor?
Birt-Hogg-Dube syndrome is a hereditary disease that usually only manifests itself in adulthood. People in whose families the Birt-Hogg-Dube syndrome has already occurred should familiarize themselves with the symptoms and the course of the disease in order to recognize the first signs as such and to discuss them with a doctor as soon as possible.
Skin lesions, especially benign skin tumors such as fibrofolliculomas, are typical of the disease. These skin changes often have the effect of red blisters or pustules on those affected, which also show up in childhood illnesses or a contact allergy. If Birt-Hogg-Dube syndrome has already occurred in the family, however, all skin changes, even if they seem harmless at first, should be presented to a doctor immediately. In doing so, the doctor must be made aware of the hereditary disease.
The prompt consultation of a doctor is particularly important because the skin lesions usually show up before the other typical symptoms, in particular lung cysts and kidney tumors, set in. While the skin changes are mostly a cosmetic problem that does not necessarily require immediate medical attention, the early detection and treatment of malignant tumors can save the patient’s life.
Treatment & Therapy
The causes of the Birt-Hogg-Dube syndrome are relatively well understood, but the role of the defective protein has so far been rather unclear. A causal therapy is not available to the patient. Since the syndrome is a genetic defect, advances in gene therapy over the next few decades could open up causal treatment approaches.
So far, however, gene therapy has not reached the clinical stage. Therefore, patients with BHD are currently being treated more or less symptomatically. The individual therapy steps therefore depend on the severity of the disease and the symptoms present in the individual case. As a supportive step, the affected patients are offered genetic counseling, which may include molecular analyzes.
The dermatological manifestations of the syndrome are treated depending on the individual case. There is no specific treatment for the skin lesions. In some cases, resection is the treatment of choice. Solitary and perifollicular fibroids, for example, must be treated using invasive procedures. These invasive procedures are equivalent to surgically removing the lesion as completely as possible.
In individual cases, applications such as dermabrasion or electro-desiccation are possible. In many cases, the skin lesions are at high risk of recurrence. Regular check-ups by a dermatologist are therefore recommended. In addition, patients with the syndrome should be checked regularly for changes in the lungs, kidneys and gastrointestinal tract.
When kidney tumors are removed, the entire kidney is usually not removed. Since those affected have an increased risk of lung cancer, they are strongly advised not to smoke.
Outlook & forecast
Birt-Hogg-Dube syndrome has a poor prognosis. It is a genetic disease that cannot be cured with current medical and scientific knowledge. What makes it more difficult is that, due to legal requirements, interference with human genetics is not permitted.
However, the chances of symptom relief without the use of medical care become even worse. The patient’s well-being and quality of life decrease significantly, as the disease is associated with numerous secondary diseases. The risk of premature death also increases significantly, since most patients suffer from cancer.
The individual complaints are treated in a medical care. The cysts or tumors that have formed are removed. In addition, the organism is given timely support in the event of deficiency symptoms. This strengthens the immune system and helps to physically cope with the disease and its sequelae.
Skin changes can be detected and diagnosed at an early stage in regular check-ups. The treatment enables the patient to improve their living conditions and extend their chances of life. In addition, the emotional and mental stability of the person affected can be promoted in psychotherapy. There the patient learns to live with the disease and can thus cope better with the challenges of everyday life.
Birt-Hogg-Dube syndrome can only be prevented by genetic counseling in the family planning phase. If the results are appropriate, couples can decide against having their own children and instead initiate adoptions.
Since Birt-Hogg-Dube syndrome is a hereditary disease, direct follow-up care is usually not possible and also not necessary. The affected person is therefore dependent on medical treatment throughout his life in order to avoid further complications. However, since Birt-Hogg-Dube syndrome significantly increases the likelihood of tumors occurring, regular examinations are necessary to prevent the tumor from spreading.
Regular visits to a dermatologist are also required to relieve the skin discomfort. In some cases, the skin complaints can be completely healed so that further treatment is no longer necessary. However, examinations for carcinomas are also necessary on the face.
Since patients with Birt-Hogg-Dube syndrome have a significantly increased risk of lung cancer, smoking should be avoided completely. In some cases with Birt-Hogg-Dube syndrome, a visit to a psychologist can also be useful to treat or prevent psychological complaints. The parents and relatives of the patient can also seek psychological treatment, as they too suffer from the disease.
A causal treatment is not possible in this syndrome. If you want to have children again, genetic counseling should be carried out in order to possibly prevent the recurrence of Birt-Hogg-Dube syndrome.
You can do that yourself
The Birt-Hogg-Dube syndrome is a genetic hereditary disease. Those affected cannot take any self-help measures that have a causal effect.
People who have had the syndrome in their families should familiarize themselves with the disease and see a qualified doctor at the first sign. The disease usually only shows up in adulthood. The first symptoms are skin lesions, which medical laypeople can confuse with an allergic rash or other harmless skin lesion. The skin lesions themselves are usually harmless, even if they are often disfiguring.
Depending on their severity, they can be removed by a dermatologist or even only concealed with cosmetic products. For other reasons, however, patients should react promptly. The skin changes usually show up before other typical symptoms of the disease set in. The characteristic symptoms include cysts and tumors, which predominantly affect the kidneys. These tumors can be malignant. The earlier they are recognized and treated, the greater the patient’s chances of recovery.
The most important contribution to self-help for those affected by Birt-Hogg-Dube Syndrome is to know and observe their own body well so that they can react quickly to pathological changes.