Hornstein-Knickenberg syndrome is a genetic disorder associated with mutation of elements of the mTOR signaling chain. Because this signaling chain affects cell growth and mortality, mutation manifests in multiple cell proliferations. The tumors manifest as multisystem disease.
What is Hornstein-Knickenberg syndrome?
Hornstein-Knickenberg syndrome was first described in the 20th century by German dermatology professor Otto P. Hornstein and assistant Monika Knickenberg. In honor of the first describers, the complex of symptoms they described was henceforth called Hornstein-Knickenberg syndrome. Because the symptom complex was also described months later by Arthur R. Birt, W. James Dubé, and Georgina R. Hogg, the clinical term Birt-Hogg-Dubé syndrome is considered a common synonym for the disorder. Because it is a rare fibroma, the syndrome is also referred to as fibromatosis cutis. Symptoms of the disease do not manifest until adulthood, although the disease is considered genetic and therefore congenital. The incidence of the disease is not well understood. However, the prevalence is estimated to be about one case in 200,000. Thus, according to these estimates, the syndrome would be more common than some other genetic disorders. The syndrome can be broadly classified as a tumorous disease, as affected individuals develop multiple and histologically distinct papules on the skin and organs. To date, the syndrome has been described in approximately 100 families.
Causes
The cause of Hornstein-Knickenberg syndrome appears to be genetics. A sex preference has not been observed. The symptom complex has also been described as hereditary as often as familial or sporadic. An autosomal dominant inheritance was observed in cases of familial clustering. The exact causes for the development of the symptoms have not been conclusively clarified. However, there are a number of speculations in this regard. The most probable assumes causative mutations in the FLCN gene at gene locus 17p11.2. This gene codes in the DNA for the protein folliculin. The function of this endogenous substance is not yet known. However, there is speculation that folliculin is an element of the mTOR signaling chain. This is the so-called mammalian Target Of Rapamycin. This signaling chain has been shown to be a critical element for cell survival, cell growth and cell mortality. When the FLCN gene is mutated, the folliculin protein is defective. If, as speculated, it is indeed an element of the mTOR signaling chain, the mutation within this signaling chain could explain the excessive cell growth and thus the symptomatic proliferations of Hornstein-Knickenberg syndrome.
Symptoms, complaints, and signs
Hornstein-Knickenberg syndrome is characterized by various, clinical features. Usually beginning around the fourth decade of life, patients suffer from skin-colored to flesh-colored, waxy dermal lesions that are up to five millimeters in size, hemispherical, and usually asymptomatic. In addition to dermal lesions, oral papules also occur. Histologically, the multiple lesions correspond to combinations of different structures. In addition to perifollicular fibromas of the trunk and head, pendulous fibromas in the groin area, axillae, or near the neck are common symptoms. In addition, adenomatous colon polyps are usually present. Tumors of the hair disc, lipomas, angiolipomas and basal cell carcinoma]e may also fit into the clinical picture as well as connective tissue nevus. In addition to dermal manifestations, the disease may also manifest itself in organic manifestations. It frequently affects the organ system with symptoms such as colon carcinomas or adenomas, prostate carcinomas, renal cysts, angiolipomas, or hyperuricemias. Emphysema of the lungs may also occur. Dasselne applies to bronchiectasis, hamartomas or lung cysts. In the eyes, retinopathy, chorioretinopathy, or glaucoma are often present. The endocrine system of patients may be affected by thyroid carcinomas and parathyroid adenomas. With regard to the endocrine system, hypothyroidism or diabetes may also develop. In addition, hypertonia of the muscles, facial paresis, progressive deafness, or aplasia of the arteries may also fit into the clinical picture.
Diagnosis and course of the disease
The first step toward diagnosis for Hornstein-Knickenberg syndrome corresponds to the identification of all clinical manifestations and findings as symptoms of the same clinical picture. Once the symptoms have been demonstrated by imaging and the physician has pinned the manifestations to one syndrome, he or she can confirm the tentative diagnosis of Hornstein-Knickenberg syndrome by detecting the mutations in the FLCN gene. The prognosis depends on the time of diagnosis, the involvement of internal organs, and the type of tumors in each case.
Complications
Cell proliferation occurs as a result of Hornstein-Knickenberg syndrome. These generally have a very negative effect on the patient’s health. Usually, this results in skin lesions, which, however, do not lead to any particular symptoms. The affected person also suffers from fibromas and tumors in various regions of the body. The internal organs can also be affected, so that without treatment the patient usually dies. Not infrequently, the eyes are also affected by Hornstein-Knickenberg syndrome, and glaucoma may occur. Furthermore, most patients suffer from diabetes and deafness. The deafness is progressive and usually develops during the course of the disease. It is not possible to treat Hornstein-Knickenberg syndrome causally. For this reason, only the symptoms and complaints of the syndrome can be limited and treated. Although there are no complications, a positive course of the disease cannot be guaranteed. In some cases, this limits the life expectancy of the patient. In most cases, patients also require psychological care to alleviate the psychological symptoms.
When should you see a doctor?
If skin lesions and oral papules are suddenly noticed, Hornstein-Knickenberg syndrome may be underlying. A visit to the doctor is indicated if the symptoms persist over a longer period of time or if further complaints occur. It is typical for the disease to appear from the fourth decade of life onwards. In most cases, the symptoms increase over the years and eventually also cause mental suffering. The genetic defect must be promptly examined and treated by a family doctor or dermatologist. Otherwise, serious complications may develop. At the latest when the characteristic tumors of the hair disc are noticed, medical advice is needed. In case of visual disturbances, it is best to consult an ophthalmologist. Organ diseases require clarification by a specialist in internal diseases. People who already suffer from diabetes or deafness should inform the responsible physician about unusual symptoms and adjust their diet in cooperation with a nutritionist. Comprehensive medical treatment supported by self-help measures can reduce the symptoms of Hornstein-Bochenberg syndrome.
Treatment and therapy
Causal therapy does not exist for patients with Hornstein-Knickenberg syndrome until gene therapy interventions are approved. For this reason, treatment is currently symptomatic and supportive. The dermatological manifestations of the syndrome cannot be specifically treated. Manifestations such as the political perifollicular fibroma are surgically removed. Therapeutically, electrodesiccation and dermabrasion have also been discussed in the past, but these are often associated with recurrences. If manifestations are already present in the organ system, these manifestations must also be surgically or microsurgically removed and, if necessary, retreated. Close monitoring is always indicated for patients with Hornstein-Knickenberg syndrome. In this way, especially assaults on the organ system should be detected in time. Supportive psychotherapeutic care is usually suggested to the patients. In addition to this step, affected individuals receive genetic counseling and, in this counseling, are especially informed about the risk of disease in planned children and similar correlations.
Prospect and prognosis
Prognosis and outlook are based on factors including the time of diagnosis, the type and number of tumors, and the extent of the disease. If the internal organs are involved, the prognosis is much more negative than if only the skin and other external organs are affected.In principle, there is a prospect of cure, provided the disease is detected and treated at an early stage. Patients have to undergo chemotherapy or radiotherapy, which can lead to further physical complaints. However, complications can be reduced by optimally adjusted medication and comprehensive follow-up care. If Hornstein-Knickenberg syndrome is diagnosed late, the prognosis is poor. By then, internal organs may already be affected and surgery and other measures must be taken, which are not always successful. However, in Hornstein-Knickenberg syndrome, there is always a chance of complete recovery. The patient must seek treatment early and also follow the doctor’s instructions. If recurrences form, the chances of recovery decrease proportionally. Life expectancy is not necessarily reduced by Hornstein-Knickenberg syndrome. Quality of life, on the other hand, is greatly reduced because the multisystem disease affects the entire body and causes multiform complaints. Painkillers and surgery can improve well-being in the long term. Nevertheless, complete recovery is unlikely, so in conclusion, Hornstein-Knickenberg syndrome does not offer a good prognosis.
Prevention
To date, it is virtually impossible to prevent Hornstein-Knickenberg syndrome. Because a hereditary basis is suspected, the only preventive measure is not to have children of one’s own if the syndrome is already known within one’s family.
Follow-up
In most cases, the patient has no or very few measures of direct aftercare available for Hornstein-Knickenberg syndrome. In this disease, a physician must be consulted immediately to prevent further complications or, in the worst case, death of the affected individual. If the syndrome is not detected early and treated by a physician, the tumors may spread. Therefore, the patient should see a doctor at the first symptoms and signs of the disease to prevent further discomfort. The symptoms themselves are usually relieved by surgical intervention. In any case, the patient should rest and take it easy on the body after such an operation. Efforts or stressful physical activities should be avoided in any case, in order not to put unnecessary strain on the body. Furthermore, regular examinations by a doctor are also very useful in order to detect and treat new tumors at an early stage. Possibly, the Hornstein-Knickenberg syndrome leads to a reduced life expectancy of the patient. Since the syndrome can also lead to psychological upset or depression, discussions with friends or family are often very useful to prevent it.
Here’s what you can do yourself
Unfortunately, the options for self-help are relatively limited in the case of Hornstein-Knickenberg syndrome, so the affected person must rely primarily on medical treatment to alleviate the symptoms. In the case of diabetes, a strict diet must be followed to avoid further complications and discomfort. In this regard, a nutritionist can also be consulted, who can provide the affected person with a diet plan. The discomfort in the area of the eyes can usually be compensated by various visual aids. Furthermore, the use of caring creams and ointments can have a very positive effect on the skin complaints of Hornstein-Knickenberg syndrome and alleviate them. However, sufferers must rely on surgical interventions to effectively combat the disease. Psychological care continues to have a positive effect on the course of the disease. This care does not necessarily have to be provided by a psychologist. Friends and relatives can also contribute to the patient’s psychological stability and alleviate depression. Especially in the case of children, a clarifying discussion about the possible course of the disease should be conducted. Furthermore, those affected should undergo genetic counseling in order to prevent Hornstein-Knickenberg syndrome in children.
