HLS stands for the 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 can also be affected.
What is Hippel-Lindau Syndrome?
The Hippel-Lindau syndrome is a very rare, benign, tumor-like tissue change, mainly in the area of the retina and cerebellum. So-called angiomas (blood sponges) occur as tumors . Therefore, the disease is often referred to as retinocerebellar angiomatosis. The brainstem and spinal cord are also often affected.
The tumors develop from precursors of the connective tissue and consist of vascular balls. They are mostly benign, but can also become malignant. Sometimes tumors are also found in the pancreas, adrenal gland, epididymis, or kidneys. Kidney tumors in particular are more likely to develop into cancer. The condition was named after the German ophthalmologist Eugen von Hippel and the Swedish pathologist Arvid Lindau. In 1904 von Hippel discovered angiomas in the retina of the eye.
22 years later, in 1926, Arvid Lindau described the angiomas in the spinal cord. In addition to the designation Hippel-Lindau syndrome, the disease 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 disorders that manifest themselves in the skin and central nervous system.
Hippel-Lindau syndrome is genetic. The disease is inherited in an autosomal dominant manner. However, the severity 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 families. Spontaneous mutation occurs in 50 percent. This means that half of the sick people in the family have no hereditary burden.
However, this means that several mutations in the HL gene on chromosome 3 can be responsible for the development of the disease. This gene has a significant impact on blood vessel development and the cell cycle. It is not just a mutation in the HL gene that leads to dysregulation of the blood vessels. In the meantime, it has been established that when the disease breaks out, there are a whole series of mutations that are distributed over the entire gene.
Symptoms, Ailments & Signs
The Hippel-Lindau syndrome generally manifests itself in exhaustion, high blood pressure and headaches. In addition, there are neurological symptoms such as balance disorders, disturbances in the coordination of movements or signs of intracranial pressure. Visual disturbances ( visual disturbances ) are often the initial symptom . However, the symptoms are largely dependent on the size and location of the tumors.
Angiomas are usually found in the retina, in parts of the central nervous system, in the spinal cord or in the brainstem. The cerebrum is rarely affected. During examinations, abnormalities are often found in other organs as well. Cysts are found particularly in the pancreas, liver or kidneys. 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. A pheochromocytoma is a benign tumor of the adrenal gland that produces increased levels of the hormones adrenaline and noradrenaline. Heart rate and blood pressure increase. Blood pressure rises at intervals and reacts particularly strongly in stressful situations.
Diagnosis & disease progression
The detection of multiple hemangiomas in the retina of the eyes is clear evidence of Hippel-Lindau syndrome. A family history provides information about a possible accumulation within the family or relatives. Imaging procedures can be used to detect any tumors in the kidneys, adrenal glands, pancreas or liver.
Various organs can be affected by Hippel-Lindau syndrome. In most cases, however, the person affected suffers from a general feeling of illness. This leads to severe headaches and the affected person looks exhausted. High blood pressure also occurs, which in the worst case can lead to a heart attack. The patient also complains of visual disturbances and restricted mobility.
The coordination of the patient can also be disturbed by the Hippel-Lindau syndrome. In many cases, the Hippel-Lindau syndrome also has a negative effect on the patient’s behavior, so that it is not uncommon for an adeptness to develop. The heart rate increases even in simple and easy situations, so that stressful situations can lead to sweating or panic attacks for the person concerned. Without treatment for Hippel-Lindau syndrome, life expectancy is usually reduced.
The syndrome cannot be treated in every case. This is especially true when the syndrome is genetic. However, symptomatic treatment can limit the symptoms and possibly remove the tumor. However, the exact course of the disease depends on the severity of the tumor. The life expectancy of the patient may therefore also be limited.
When should you go to the doctor?
In case of a general feeling of illness, malaise or exhaustion, a precise self-observation should be carried out. If there is persistent tiredness despite a restful night’s sleep, this is a sign of a health problem. If the symptoms persist for several weeks, there is a reason for a check-up. If existing symptoms spread or increase in intensity, a doctor should be consulted. If you have high blood pressure, coordination disorders or motor movement processes, you should consult a doctor.
If your blood pressure rises to an unusually high level, especially in stressful life situations, you need to see a doctor. 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 back area, a drop in physical performance and a diffuse pain experience must be clarified by a doctor.
If the symptoms appear without a reason, the person concerned needs a medical examination. In the case of functional disorders of the gastrointestinal tract, a feeling of heat or mood swings, a consultation with a doctor is recommended. Complaints in the kidney region or abnormalities when urinating are considered warning signals from the body that should be followed up.
Treatment & Therapy
Since Hippel-Lindau syndrome is a genetic disease, causal treatment is not possible. However, existing angiomas can be removed through various procedures. These include laser coagulation, cryotherapy, brachytherapy, transpupillary thermotherapy, photodynamic therapy, radiation therapy, proton therapy or drug treatment. In laser therapy, small angiomas are denatured by local overheating. The diseased tissue dies and heals at this point.
Cryotherapy uses temperatures down to minus 80 degrees to freeze peripheral angiomas in the retina. Brachytherapy uses radioactive radiation to destroy angiomas. Transpupillary thermotherapy can be used for retinoblastoma, choroidal melanoma, or choroidal hemangioma. It works on the basis of heating the tumor with infrared radiation. In the case of angiomas, the presentation of treatment successes is contradictory. Some studies have reported successes in treating angiomas. In other studies, the treatment was ineffective.
Photodynamic therapy uses light in combination with a light-active substance. Verteporfin is used as the light-active substance in current studies. An improvement in eyesight is noted. However, macular edema can occur. Radiation therapy shows no drastic successes. Vision can be improved, but not all tumors shrink evenly. The best results are achieved with small angiomas. Proton therapy works with very high precision. It is used when the angiomas are near sensitive tissue sites.
Outlook & Forecast
The prognosis for Hippel-Lindau syndrome depends largely on the type and location of the various tumors. An average age of 50 years was determined as the mean life expectancy. However, life expectancy and quality of life can be significantly increased through early detection and treatment of the tumors. Although the tumors initially represent only deformations of the connective tissue on the blood vessels and are benign, some of them can transform into a malignant tumor. Kidney carcinomas, which are a main reason for the high mortality, then develop particularly frequently.
Pancreatic carcinomas (cancer of the pancreas) and carcinomas in 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 can lead to cerebral hemorrhage. The general symptoms such as high blood pressure, headaches and fatigue as well as the neurological symptoms also depend on the individual tumors.
Some patients have no symptoms if central nervous system hemangioblastomas are not present. As the disease progresses, hemangioblastomas in the retina can lead to retinal problems and even complete blindness. Furthermore, tumors can occur in about 10 percent of patients, causing complete hearing loss. The course of the disease can vary so much that an exact prognosis for the individual affected is not possible.
There is no prevention of Hippel-Lindau syndrome because it is a genetic disease. If there is a family history of the disease, human genetic counseling should be carried out if you wish to have children.
After being diagnosed with Hippel-Lindau syndrome, the whole life of those affected changes. From now on you have to keep a close eye on your body and consult a doctor for any newly formed lumps. The earlier masses are treated, the greater the likelihood of good treatment success and the fewer the complications.
Patients must have regular check-ups throughout their lives. Since new masses can appear anywhere in the body, they must be performed by doctors from different specialties. In annual general clinical examinations, all palpable masses are discussed, blood pressure measured and further therapy discussed. Annual ophthalmological examinations enable the early detection of retinal hemangioblastomas.
The urine collected is also checked annually, which can be used to diagnose pheochromocytomas. MRI scans of the head and spinal cord are performed every three years to image and treat spinal hemangioblastoma. An MRI of the abdomen also serves 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 type and spread diagnostics of tumors. In individual cases, a catheter examination of blood vessels may also be necessary in order to obliterate the vessels leading to the tumor and to facilitate later therapy.
You can do that yourself
In the case of the Hippel-Lindau syndrome, the person affected has no special options for self-help. Unfortunately, the syndrome cannot be prevented or treated causally either, so that only symptomatic treatment is given. 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 surgically. The type of intervention depends heavily on the location and severity of the tumor. As a rule, however, the life expectancy of those affected is not reduced by the Hippel-Lindau syndrome, since the tumors can be removed and are benign. Psychological upsets or depression can often be avoided by talking to other sufferers or to close friends and relatives. Especially with children, an informative conversation should always take place in order to enlighten them about the possible consequences of the disease.
In most cases, treatment for Hippel-Lindau syndrome can also improve the sufferer’s vision. However, they continue to be dependent on visual aids in order to be able 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.