Vhl mutations predispose to the development of a variety of tumours most commonly retinal and central nervous system haemangioblastomas, clear cell renal carcinoma and phaeochromocytomas. Mutation or loss of both vhl alleles has been documented in sporadic renal cell. Although the majority of tumors occur in adults, children and adolescents with the condition develop a significant proportion of vhl manifestations and are. The principal feature is a single or multiple tumour of bloodforming tissue haemangioblastoma in the retina, the cerebellum, the brainstem or the spinal cord. Vhl disease most frequently affects the eyes, cerebellum, kidneys, spinal cord, adrenal gland or pancreas. It is characterized by visceral cysts and benign tumors with potential for subsequent malignant transformation. A germline mutation in the vonhippel lindau vhl gene predisposes carriers to development of abundantly vascularised. Vhl disease demonstrates agedependent and incomplete penetrance and variable expression 4,5,6. Ultimately, such insight will improve the diagnostics, surveillance and treatment of vhl patients.
Novel genotypephenotype correlations in five chinese families. However, cases with this triad syndrome are more advanced and rare. Read more about symptoms, diagnosis, treatment, complications, causes and prognosis. A vhl database study supported by the vhl alliance was recently published from toronto canada pmid 3682. It is caused by germline mutations of the tumor suppressor gene vhl, located on. In cases of vhl disease undergoing annual surveillance, the early detection and treatment pathways for symptomatic retinal. These tumors can be either benign noncancerous and malignant cancerous. Vhls is associated with the presence of vascular tumors, often hemangioblastoma of the central nervous system, retina, or spinal cord and, less frequently, pancreatic cystic neoplasm, pancreatic neuroendocrine tumor, clear. The most important lesions are hemangioblastomas of the retina, cerebellum, brain stem, and spinal cord. These tumors may be benign or malignant but can often cause other problems depending on where they are located in the body. Early microsurgical treatment for spinal hemangioblastomas. Increased renal cancer clear cell renal cell carcinoma. The aim of the current study is to demonstrate the benefit of early surgical resection of large spinal hbs in selected asymptomatic patients with vhl.
It is caused by germline mutations of the tumor suppressor gene vhl, located on the short arm of chromosome 3. Similar to other tumor suppressor gene disorders, vhl disease is characterized by frequent development of specific types of tumors in selective organs. This is the only gene currently known to cause vhl. These abnormal growths can further develop into tumors and cysts. Abstract 1934 html downloads 3418 pdf downloads 776 xml. Vonhippellindaus disease vhl is a rare autosomal dominant disorder with. Vhl disease effects 1 in 36,000 people 10,000 cases in the u. It can affect several different parts of the body and cause several types of problems. But some tumors, such as those in the kidney and pancreas, can become cancerous. They can grow in your brain and spinal cord, kidneys, pancreas, adrenal glands, and reproductive tract.
European society of endocrinology clinical practice. Loss of function variants in vhl are the only known cause of vhl, and germline vhl variants can be detected in up to 100% of vhl families. Hemangioblastomas that develop in the brain and spinal cord can cause headaches, vomiting, weakness, and a loss of muscle coordination ataxia. This disorder is not rare about one in 36 000 livebirths and is inherited as a highly penetrant autosomal dominant trait ie, with a high individual risk of disease. It is characterized clinically by vascular tumors, including retinal and central nervous system hemangioblastomas cerebellar, spinal, and brain stem. Clinical hallmarks of vhl disease include the development of retinal and central nervous system cns hemangioblastomas blood. Four missense mutations in vhl have been identified in 21.
The most common pathological lesions are hemangioblastomas of the central nervous system, retinal angiomas, renal clear cell carcinomas, and pheochromocytomas. Inherited in an autosomal dominant manner, it arises from germline mutations in the vhl gene. Vhl is an autosomal dominant disorder, with a prevalence. It is caused by a flaw in one gene, the vhl gene, which regulates cell growth causing patients to battle a series of tumors throughout their life. This flaw, for which the cause is unknown, leads to the abnormal growth of. A 37yearold man, who complained about a headache, nausea, and vomiting, was referred to our hospital. Hallmark lesions include retinal angiomas, hemangioblastomas of the cerebellum and spinal cord, and renal cell carcinomas. European journal of endocrinology 2016 174, g1g10 european journal of endocrinology clinical practice guideline p f plouin and others ese guidelines on ppgl followup 174. Pheochromocytoma, pancreatic neuroendocrine tumours and papillary cystadenoma of the epididymis.
Slowgrowing hemgioblastomas benign tumors with many blood vessels may develop in the brain, spinal cord, the. Although most of the tumors are benign, individuals with vhl have an increased risk of several types of cancer, including renal carcinoma and pancreatic neuroendocrine tumors. Central nervous system and retina tumors called hemangioblastomas. The general hallmarks of a hereditary endocrine neoplasia predisposition syndrome include any one of the following.
Lindau vhl syndrome omim 193300 is an autosomal dominant disorder caused by deletions or mutations in a tumor suppressor gene mapped to human chromosome 3p25. Slowgrowing hemgioblastomas benign tumors with many blood vessels may develop in the brain, spinal cord, the retinas of the eyes, and near the inner ear. The incidence of vhl disease is assessed about one in 36,000 livebirths and the penetrance is higher than 90%. Vhl disease is an inherited disorder that causes tumors and cysts to grow in certain areas of the body, including the central nervous system including the brainstem, cerebellum, and spinal cord, retina, endolymphatic sac in the ear, adrenal glands, pancreas, kidneys, epididymis in males, and broad ligament in females. In this disease, the vhl protein becomes inactivated by germline mutations of the vhl tumor suppressor gene on chromosome 3p2526, resulting in an overproduction of vegf in nonhypoxic conditions. The gene product, pvhl, has multiple functions, but the best documented, and the one most clearly linked to tumor development, relates to its role as the substrate recognition module of. Vhl causes cysts and tumours to develop in various organs from late childhood. The hormonal and hemodynamic changes in pregnancy accelerate the growth of hemangioblastomas, leading to increased symptoms and consequent risk to the mother and fetus.
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