Von Hippel-Lindau syndrome (VHL) is a rare, genetically determined disease that is inherited in an autosomal dominant fashion. The most common group of changes in the course of VHL are fetal hemangiomas of the retina and the central nervous system, and pancreatic cysts. What are the symptoms of von Hippel-Lindau syndrome? How is the treatment going?

von Hippel-Lindau syndrome(von Hippel-Lindau disease, von Hippel-Lindau syndrome, HLS, VHL, familial cerebelloretinal angiomatosis, Latin. hemangioblastomatosis, angiophakomatosis retinae et cerebelli) is characterized by the presence of embryonic hemangiomas (hemangioblastoma) in the cerebellar hemispheres, the retina and, less frequently, in the brainstem, spinal cord and nerve roots. Visceral tumors and cysts may also be present in organs such as the pancreas, liver, and kidneys. Patients are also at increased risk of developing renal cell carcinoma. This syndrome affects 1 in 30,000-40,000 people.

Von Hippel-Lindau syndrome: causes

The disease is caused by mutations in the VHL suppressor gene on chromosome 3. This gene codes for a protein, part of the ubiquitin-ligase complex, that marks the degradation of the transcription factor HIF (hypoxia-inducible factor). This factor has many different features, such as promoting cell survival under stress, stimulating angiogenesis, and increasing erythropoiesis and glycolysis. In von Hippel-Lindau syndrome, the function of the protein encoded by the VHL gene is completely lost, which is associated with a high level of HIF. This creates perfect conditions for the formation and development of cancer.

Von Hippel-Lindau syndrome: symptoms

In von Hippel-Lindau syndrome, the initial symptoms usually result from the presence of vascular anomalies in the central nervous system, but in some patients the first manifestation of the disease may be symptoms of a phaeochromocytoma or a tumor of the kidney, pancreas, liver or epididymis.

The most common group of changes in the course of VHL are fetal hemangiomas of the retina and the central nervous system, and pancreatic cysts.

Fetal hemangiomas are benign, slow-growing vascular neoplasms and their symptoms aredue to hemorrhages or a mass effect at the site of growth. Histologically, they are composed of vascular channels lined with endothelium, surrounded by stromal cells and pericytes. There are also mast cells that can produce erythropoietin. This may result in the development of polycythemia as a paraneoplastic syndrome.

In spinal cord hemangiomas, there is usually focal back or neck pain, sensory disturbances and paresis.

Retinal hemangiomas may be asymptomatic, especially when they occur around the periphery of the retina. Loss of vision may occur if the lesions are large and central. Haemorrhage can result in retinal damage and detachment, glaucoma, uveitis, macular edema, and sympathetic eye inflammation. Fetal cerebral hemangiomas are present in less than 5 percent of VHL patients and are most common in the cerebellum, medulla, and bulb. Initial symptoms usually include headache, followed by ataxia, nausea and vomiting, and nystagmus. Symptoms are often decelerating or slowly progressive, but approximately 20% of patients experience an acute onset, usually after a minor head injury.

Renal cysts are present in more than half of patients and are usually asymptomatic. Extensive cysts rarely lead to failure. More attention is being paid to renal cell carcinoma, which develops in approximately 70% of affected patients and is a major cause of death. These tumors are usually multiple and tend to occur at a younger age than sporadic ones.

Pheochromocytomas may be the only clinical manifestation of the disease. It happens that they are bilateral and occur outside the adrenal glands. They may manifest as paroxysmal or persistent arterial hypertension, severe headaches, as well as hot flashes and redness with increased sweating. In advanced stages, hypertensive crises, stroke, myocardial infarction, and heart failure may occur.

Pancreatic and epididymis cysts and tumors may also occur in the course of von Hippel-Lindau syndrome. The pancreas contains neoplasms of non-secretory pancreatic islet cells, ordinary cysts, microcystic serous adenomas and glandular carcinomas. Fortunately, asymptomatic pancreatic cysts are the most common and present symptoms when the bile duct is obstructed. It should be borne in mind that numerous pancreatic cysts can cause pancreatic failure.

von Hippel-Lindau syndrome: diagnosis

Fetal hemangiomas of the brain and spinespinal cord is diagnosed on the basis of imaging tests. For this purpose, magnetic resonance imaging with contrast is used. Arteriography is not necessary for diagnosis, but can be useful in identifying afferent vessels in cases where surgery is planned.

The diagnosis of pheochromocytoma is based on the detection of excessive levels of catecholamines in the serum and urine. Norepinephrine and adrenaline are elevated in both serum and urine, and vanillin-mandelic acid in urine.

Von Hippel-Lindau syndrome: treatment

Unfortunately, there is no treatment for the causal von Hippel-Lindau syndrome. The mainstay of therapy is the surgical removal of tumors. Small or slow-growing hemangiomas do not require treatment, only observation. On the other hand, large and rapidly growing hemangiomas or those that cause symptoms require surgical removal, or radiotherapy.

Kidney tumors larger than 3 cm in diameter or rapidly growing kidney tumors are surgically removed.

In the case of retinal hemangiomas, laser photocoagulation or cryotherapy is used. Vitrectomy should be considered in patients with retinal detachment.

Screening for von Hippel-Lindau syndrome is very important. This is especially true for patients with liver cysts, multiple or bilateral kidney tumors, multiple retinal hemangiomas and cerebellar hemangiomas. Also, do not forget about the testing of first-degree relatives in a family with VHL or phaeochromocytoma.

Category:

Genetic diseases