Hippel-Lindau syndrome is a hereditary benign tumor disease primarily of the retina and cerebellum. It is due to a malformation of the blood vessels. Other organs may also be affected.
What is Hippel-Lindau syndrome?
Hippel-Lindau syndrome represents a very rare benign tumor-like tissue change mainly in the retina and cerebellum. So-called angiomas (blood sponges) occur as tumors. Therefore, the disease is often called retinocerebellar angiomatosis. The brainstem and spinal cord are also often affected. The tumors develop from preforms of connective tissue and consist of vascular tangles. They are usually benign, but can also degenerate malignantly. Sometimes tumors are also found in the pancreas, adrenal gland, epididymis or kidneys. Especially the kidney tumors can develop into cancer more often. The disease was named after the German ophthalmologist Eugen von Hippel and the Swedish pathologist Arvid Lindau. Von Hippel discovered angiomas in the retina of the eye in 1904. 22 years later in 1926, Arvid Lindau described angiomas in the spinal cord. In addition to the name Hippel-Lindau syndrome, the condition is also known as Von Hippel-Lindau-Czermak syndrome, Hippel-Lindau disease, retinocerebellar angiomatosis, or retinal angiomatosis. It is a neurocutaneous syndrome characterized by vascular malformations in various organs. Neurocutaneous syndromes are diseases that manifest in the skin and central nervous system.
Causes
Hippel-Lindau syndrome is genetic. In this case, the disease is inherited in an autosomal dominant manner. However, the expression of the syndrome depends on many other factors. Although the genetic defect is passed on to the next generation, the severity of the disease varies within the family. A spontaneous mutation occurs in 50 percent of cases. Thus, in half of those with the disease, there is no hereditary burden in the family. However, this means that several mutations of the HL gene on chromosome 3 can be responsible for the development of the disease. This gene has a significant influence on the development of blood vessels and the cell cycle. It is not only a mutation on the HL gene that leads to a dysregulation of the blood vessels. It has now been established that a whole series of mutations are present at the onset of the disease, distributed throughout the gene.
Symptoms, complaints, and signs
Hippel-Lindau syndrome generally manifests as fatigue, hypertension, and headaches. In addition, there are neurologic symptoms such as balance disorders, disturbances in motor coordination, or signs of intracranial pressure. The initial symptom is often visual disturbances (visual disturbances). However, the symptoms are essentially dependent on the size and the localization of the tumors. Most often, angiomas are found in the retina, in parts of the central nervous system, in the spinal cord or in the brain stem. The cerebrum is very rarely affected. During examinations, malformations are often found in other organs as well. Cysts are found especially in the pancreas, liver or kidneys. Furthermore, benign arteriovenous vascular malformations are also present in the liver. When the adrenal glands are affected by an angioma, a pheochromocytoma develops. There are forms of Hippel-Lindau syndrome with and without pheochromocytoma. Pheochromocytoma is a benign tumor of the adrenal gland that produces increased levels of the hormones adrenaline and noradrenaline. Thereby heart rate and blood pressure are increased. Blood pressure rises in intervals and reacts particularly strongly in stressful situations.
Diagnosis and course of the disease
Detection of multiple hemangiomas in the retina of the eyes is definitive evidence of Hippel-Lindau syndrome. A family history provides information about any clustering within the family or relatives. Imaging can detect any tumors in the kidneys, adrenal glands, pancreas, or liver.
Complications
Various organs may be affected by Hippel-Lindau syndrome. In most cases, however, the affected person suffers from a general feeling of illness. Severe headaches occur, and the affected person appears fatigued. Furthermore, high blood pressure occurs, which in the worst case can lead to a heart attack.The patient also complains of visual disturbances and movement restrictions. The patient’s coordination may also be disturbed by Hippel-Lindau syndrome. In many cases, Hippel-Lindau syndrome also has a negative effect on the patient’s behavior, so that it is not uncommon for the patient to become unhinged. The heart rate increases even in simple and easy situations, so that stressful situations for the affected person can lead to sweating or panic attacks. Without treatment for Hippel-Lindau syndrome, life expectancy is usually reduced. Treatment of the syndrome is not possible in every case. This is especially true when the syndrome is genetic. However, symptomatic treatment can limit the symptoms and possibly remove the tumor. The exact course of the disease, however, depends on the extent of the tumor. Therefore, the patient’s life expectancy may also be limited.
When should you go to the doctor?
If there is a general feeling of illness, malaise, or fatigue, close self-observation should be performed. If there is persistent fatigue despite a restful night’s sleep, this is a sign of a health problem. If the complaints persist for several weeks, there is reason for a check-up. If existing symptoms spread or increase in intensity, a doctor should be consulted. If blood pressure is elevated, or if coordination or motor movements are disturbed, a doctor should be consulted. If the blood pressure rises unusually, especially in stressful life situations, a visit to the doctor is necessary. If there is a feeling of pressure inside the head, headaches, visual disturbances or a restriction of the auditory system, there is cause for concern. In severe cases, there is complete hearing loss. This should be investigated and treated as soon as possible. Problems in the area of the back, a decrease in physical performance and a diffuse experience of pain should be clarified by a physician. If the complaints occur for apparently no reason, the affected person needs a medical examination. In case of dysfunctions of the gastrointestinal tract, a feeling of heat or fluctuations in mood, a consultation with a physician is recommended. Complaints in the kidney region or abnormalities in urination are considered to be warnings from the body that should be followed up.
Treatment and therapy
Because Hippel-Lindau syndrome is a genetic disorder, causative treatment is not possible. However, existing angiomas can be removed by various procedures. These include laser kaogulation, cryotherapy, brachytherapy, transpupillary thermotherapy, photodynamic therapy, radiation therapy, proton therapy, or drug treatment. In laser therapy, smaller angiomas are caused to denature by local superheating. The diseased tissue dies and heals at that site. Cryotherapy uses temperatures as low as minus 80 degrees to ice peripherally located angiomas in the retina. Brachytherapy uses radioactive radiation to destroy angiomas. Transpupillary thermotherapy can be used for retinoblastomas, choroidal melanomas or choroidal hemangiomas. It works on the basis of heating the tumor by infrared radiation. In angiomas, the presentation of treatment successes is contradictory. For example, some studies have reported success with angioma treatment. In other studies, treatment was ineffective. Photodynamic therapy uses light in combination with a light-active substance. The light-active substance used in current studies is verteporfin. An improvement in visual acuity is observed. However, macular edema may occur. Radiation therapy does not show any breakthrough success. Visual acuity can be improved, although not all tumors shrink equally. The best success is achieved with small angiomas. Proton therapy works with very high precision. It is used when angiomas are near sensitive tissue sites.
Outlook and prognosis
The prognosis for Hippel-Lindau syndrome depends largely on the type and location of the various tumors. A mean life expectancy of 50 years has been established.However, life expectancy and quality of life can be significantly increased by early detection and treatment of the tumors. Although at the beginning the tumors are merely deformations of the connective tissue on the blood vessels and are benign, some of them can transform into a malignant tumor. Kidney carcinomas then develop particularly frequently and are a major reason for the high mortality rate. Pancreatic carcinomas (cancer of the pancreas) and carcinomas of other organs also occur. Pancreatic cancer is one of the particularly aggressive tumors that quickly lead to death. Another common cause of death is hemangioblastoma in the brain, which may lead to cerebral hemorrhage. General symptoms such as high blood pressure, headache and fatigue, and neurological symptoms also depend on the individual tumors. Some patients do not suffer symptoms when there are no hemangioblastomas yet present in the central nervous system. Hemangioblastomas in the retina can lead to retinal problems and even complete blindness as the disease progresses. Furthermore, about 10 percent of patients may develop tumors that cause complete hearing loss. The course of the disease can vary so much that an accurate prognosis for the individual affected is not possible.
Prevention
There is no prevention of Hippel-Lindau syndrome because it is a genetic disorder. If there is a family history of the disease, human genetic counseling should be performed if the patient wishes to have children, he said.
Follow-up
After being diagnosed with Hippel-Lindau syndrome, the whole life changes for affected individuals. Henceforth, they must keep a close watch on their bodies and consult a doctor for clarification whenever a new lump is formed. The earlier tumors are treated, the greater the likelihood of successful treatment and the fewer complications. Patients need to have regular examinations throughout their lives. Because new masses can appear anywhere in the body, they must be performed by physicians in a variety of specialties. Annual general clinical examinations include discussion of all palpable space-occupying lesions, measurement of blood pressure, and discussion of further therapy. Annual ophthalmologic examinations allow early detection of retinal hemangioblastomas. Also annually, a check of collected urine is performed, by means of which pheochromocytomas can be diagnosed. MRI examinations of the head and spinal cord are performed every three years to image and treat spinal hemangioblastomas. An MRI of the abdomen is additionally used to rule out pheochromocytomas, renal cell carcinomas and pancreatic tumors. Under certain circumstances, the treating physicians also use other examination methods such as positron emission tomography or single photon emission tomography or scintigraphy to supplement the diagnosis of the type and spread of tumors. In individual cases, this may also require catheterization of blood vessels to obliterate the vessels leading to the tumor and facilitate subsequent therapy.
What you can do yourself
In Hippel-Lindau syndrome, there are no particular self-help options available to the affected person. Unfortunately, the syndrome also cannot be prevented or treated causally, so only symptomatic treatment is available. However, even after successful treatment, the patient is often dependent on regular examinations in order to diagnose and treat further tumors at an early stage. The tumors are usually removed by surgery. The type of surgery depends largely on the location and extent of the tumor. However, Hippel-Lindau syndrome does not usually reduce the life expectancy of the affected person, as the tumors can be removed and are benign. Often psychological upsets or depression can be avoided by talking to other affected persons or to the closest friends and relatives. Especially in the case of children, an informative conversation should always take place to educate them about the possible consequences of the disease. In most cases, treatment of Hippel-Lindau syndrome can also improve the vision of the affected person. However, these patients continue to rely on visual aids to cope with everyday life. Due to the high blood pressure, stressful situations and strenuous sports or activities should be avoided.This protects the patient’s circulation and heart.
