According to abbreviationfinder, Hornstein-Knickenberg syndrome is a genetic disorder associated with mutation of elements of the mTOR signaling cascade. Because this signaling cascade affects cell growth and mortality, a mutation manifests itself in multiple cell proliferation. The tumors manifest themselves as a 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. The complex of symptoms they described was henceforth called Hornstein-Knickenberg syndrome in honor of the first descriptors.
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 a common synonym for the disease. Since it is a rare fibroid disease, the syndrome is also referred to as fibromatosis cutis. The symptoms of the disease do not manifest themselves until adulthood, although the disease is considered to be a genetic and therefore congenital disease.
The incidence of the disease has not been clarified in detail. However, the prevalence is estimated at around one case in 200,000. According to these estimates, the syndrome would be more common than some other genetic diseases. The syndrome can be assigned to tumorous diseases in the broadest sense, since those affected develop multiple and histologically different papules on the skin and organs. So far, the syndrome has been described in around 100 families.
Causes
The cause of Hornstein-Knickenberg syndrome appears to be genetic. A gender preference could not be observed. The symptom complex has also been described as hereditary as often as familial or sporadic. In cases of familial accumulation, an autosomal dominant inheritance has been observed. The exact causes of the development of the symptoms have not been finally clarified.
However, there is a lot of speculation about this. The most likely assumes causative mutations in the FLCN gene at gene locus 17p11.2. This gene codes for the protein folliculin in the DNA. 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 cascade has been shown to be a critical element in cell survival, growth and mortality. If there is a mutation in the FLCN gene, the folliculin protein is defective. If, as speculated, it actually represents an element of the mTOR signaling chain, the mutation within this signaling chain could explain the excessive cell growth and thus the symptomatic proliferation of Hornstein-Knickenberg syndrome.
Symptoms, Ailments & Signs
Hornstein-Knickenberg syndrome is characterized by various clinical features. From about the fourth decade of life, patients usually suffer from skin-colored to flesh-colored, waxy skin lesions that are up to five millimeters in size, hemispherical and usually asymptomatic.
In addition to the dermal lesions, oral papules also occur. Histologically, the multiple lesions correspond to combinations of different structures. In addition to perifollicular fibroids of the trunk and head area, oscillating fibroids in the groin area, on the armpits or near the neck are common symptoms. In addition, adenomatous colon polyps are usually present. Tumors of the hairy disc, lipomas, angiolipomas and basal cell carcinoma ]e can also fit into the clinical picture, as can connective tissue nevus.
In addition to the dermal manifestations, the disease can also manifest itself in organic manifestations. It often affects the organ system with symptoms such as colon carcinomas or adenomas, prostate carcinomas, renal cysts, angiolipomas or hyperuricemia. Emphysema of the lungs can also occur. The same applies to bronchiectasis, hamartomas or pulmonary cysts.
In the area of the eyes, retinopathy, chorioretinopathy or glaucoma are often present. Patients’ endocrine system may be affected by thyroid carcinoma and parathyroid adenoma. With regard to the endocrine system, hypothyroidism or diabetes can also occur. In addition, hypertonia of the muscles, facial paralysis, progressive deafness, or aplasia of the arteries can also fit into the clinical picture as accompanying symptoms.
Diagnosis & disease progression
The first step in diagnosing Hornstein-Knickenberg Syndrome is to identify all clinical manifestations and findings as symptoms of the same condition. If the symptoms are detected by imaging and the doctor has identified the manifestations of a syndrome, he can confirm the suspected 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 tumor in the individual case.
Complications
Hornstein-Knickenberg syndrome causes cell proliferation. These generally have a very negative effect on the health of the patient. As a rule, this leads to skin lesions, which, however, do not lead to any particular symptoms. The affected person also suffers from fibroids and tumors in various regions of the body.
The internal organs can also be affected, so that if left untreated, the patient usually dies. It is not uncommon for the eyes to be affected by Hornstein-Knickenberg syndrome, and glaucoma can occur. Furthermore, most patients suffer from diabetes and deafness. The deafness is progressive and usually develops over the course of the disease.
It is not possible to treat the Hornstein-Knickenberg syndrome causally. For this reason, only the symptoms and signs 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 reduces the life expectancy of the patient. In most cases, patients also need psychological care to alleviate the psychological symptoms.
When should you go to the doctor?
If skin lesions and oral papules are suddenly noticed, Hornstein-Knickenberg syndrome may be the underlying cause. A doctor’s visit is indicated if the symptoms persist over a longer period of time or other symptoms occur. It is typical for the disease that it occurs from the fourth decade of life. In most cases, the symptoms increase over the years and eventually also cause mental illness. The genetic defect must be promptly examined and treated by a general practitioner or dermatologist. Otherwise, serious complications can develop.
At the latest when the characteristic tumors of the hair disc are noticed, medical advice is required. In the case of visual disturbances, it is best to consult an ophthalmologist. Organ diseases require clarification by a specialist in internal diseases. Individuals who already have diabetes or deafness should report any unusual symptoms to their healthcare practitioner and work with a nutritionist to adjust their diet. Comprehensive medical treatment, supported by self-help measures, can reduce the symptoms of Hornstein-Knochenberg syndrome.
Treatment & Therapy
There is no causal therapy for patients with Hornstein-Knickenberg syndrome as long as gene therapy measures are not approved. For this reason, treatment is currently symptomatic and supportive. The dermatological manifestations of the syndrome cannot be specifically treated. Manifestations such as political perifollicular fibroma are surgically removed.
In the past, electrodesiccation and dermabrasion were also discussed as therapeutic options, although these are often associated with recurrences. If there are already manifestations in the organ system, these manifestations must also be surgically or microsurgically removed and, if necessary, post-treated. Close-meshed check-ups are always indicated for patients with Hornstein-Knickenberg syndrome.
In this way, attacks on the organ system in particular should be recognized in good time. Supportive psychotherapeutic care is usually suggested to the patient. In addition to this step, those affected receive genetic counseling and are informed in this counseling primarily about the disease risk of planned children and similar connections.
Outlook & Forecast
The prognosis and outlook are based, among other things, on 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 significantly more negative than when the skin and other external organs are only affected. In principle, there is a chance of healing if the disease is recognized and treated early. Patients have to undergo chemotherapy or radiation therapy, which can lead to other physical symptoms. However, the complications can be reduced by optimally adjusted medication and comprehensive aftercare.
If Hornstein-Knickenberg syndrome is recognized late, the prognosis is poor. Then internal organs may already be affected and operations and other measures must be taken, which are not always successful. However, with Hornstein-Knickenberg syndrome there is always a chance of a full recovery. The patient must be treated early and also comply with the doctor’s specifications. As recurrences form, the chances of recovery decrease proportionately. Life expectancy is not necessarily limited by Hornstein-Knickenberg syndrome.
The quality of life, on the other hand, is greatly reduced because the multisystem disease affects the entire body and causes a variety of symptoms. Painkillers and surgery can improve well-being in the long term. However, full recovery is unlikely, which is why Hornstein-Knickenberg syndrome does not conclusively offer a good prognosis.
Prevention
So far, Hornstein-Knickenberg syndrome can hardly be prevented. Since a hereditary basis is suspected, the only preventive measure is not to have children if the syndrome is already known in one’s family.
Aftercare
In most cases, patients with Hornstein-Knickenberg syndrome have no or only very few direct follow-up measures available. In the case of this disease, a doctor must be consulted immediately to prevent further complications or, in the worst case, death of the person concerned. If the syndrome is not recognized early and treated by a doctor, the tumors can spread.
Therefore, the patient should consult a doctor at the first symptoms and signs of the disease in order to prevent further complaints. The symptoms themselves are usually alleviated by surgery. The patient should definitely rest after such an operation and take care of the body.
In any case, exertion or stressful physical activities should be avoided in order not to unnecessarily burden the body. Furthermore, regular examinations by a doctor are very useful in order to detect and treat new tumors early. The Hornstein-Knickenberg syndrome may lead to a reduced life expectancy for the patient. Since the syndrome can also lead to psychological upsets or depression, talking to friends or family is often very useful to prevent this.
You can do that yourself
Unfortunately, the options for self-help with Hornstein-Knickenberg syndrome are relatively limited, so that the person affected is primarily dependent on medical treatment to alleviate the symptoms.
In the case of diabetes, a strict diet must be followed to avoid further complications and discomfort. A nutritionist can also be consulted, who can draw up a nutrition plan for the person concerned. The discomfort in the area of the eyes can usually be compensated by various visual aids. Furthermore, the use of nourishing creams and ointments can have a very positive effect on and alleviate the skin problems associated with Hornstein-Knickenberg syndrome. However, those affected are dependent on surgical interventions to effectively combat the disease.
Psychological support continues to have a positive effect on the course of the disease. This support does not necessarily have to be provided by a psychologist. Friends and relatives can also contribute to the psychological stability of the patient and alleviate depression. Especially with children, a clarifying discussion about the possible course of the disease should be carried out. Furthermore, those affected should undergo genetic counseling to avoid Hornstein-Knickenberg syndrome in children.