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Did you know how Von Hippel–Lindau disease affects your vision and balance?
Von Hippel–Lindau disease (VHL), also known as Von Hippel–Lindau syndrome, is a rare genetic disorder involving a series of problems in multiple systems. This condition is characterized by visceral cysts and benign tumors with a potential risk of malignant transformation. VHL disorders are caused by mutations in the Von Hippel–Lindau tumor suppressor gene located on chromosome 3p25.3.
Signs and symptoms
Signs and symptoms of VHL disease include headaches, balance and walking problems, dizziness, weakness, vision problems, and high blood pressure. The disease may also cause the following health conditions:
"About 40% of patients with VHL disease are accompanied by hemangioblastoma of the central nervous system, and it can be found in 60-80% of people."
Among them, retinal hemangioblastoma (angiomatosis) occurs in 37.2% of patients, which causes vision loss is quite common. In addition, other organs may be affected, and common side effects include stroke, heart disease, and cardiovascular disease. Most VHL patients begin to experience symptoms in their twenties, which profoundly affects their quality of life and daily activities.
Pathological mechanism
VHL disease is caused by mutations in the VHL tumor suppressor gene on the short arm of chromosome 3. These mutations include more than 1,500 germline and somatic mutations. There are two copies of the gene in each human body, and if one of them is mutated, it will lead to the production of a dysfunctional VHL protein (pVHL). However, normal genes can still produce functional proteins, making the disease inherited in an autosomal dominant manner. If a parent carries the defective gene, their children have an increased risk of developing tumors.
Function of VHL protein
VHL protein (pVHL) plays a crucial role in oxygen regulation. Especially under physiological conditions with oxygen, pVHL can recognize and bind HIF1α and promote its degradation. On the contrary, under hypoxic conditions or VHL gene mutations, HIF1α chooses to bind to HIF1β, thereby activating the transcription of multiple genes, which may further affect the development of tumors.
Diagnostic methods
When diagnosing VHL disease, depending on the patient's family history, specialized tumor testing can improve the efficiency of diagnosis. In the presence of a family history, the presence of a hemangioblastoma, pheochromocytoma, or renal cell carcinoma is sufficient to confirm the diagnosis. Patients with no family history need to be tested for at least two tumors to confirm the diagnosis. In addition, genetic tests such as Southern blot and gene sequencing can also be used for diagnosis, providing patients with a clearer clinical path.
Classification of VHL disease
The classification of VHL disease is mainly based on whether it is accompanied by pheochromocytoma. There are two classifications of VHL: VHL type 1 without pheochromocytoma, while VHL type 2 includes individuals with pheochromocytoma and is further subdivided into three subtypes: 2A, 2B, and 2C.
Treatment methods
Early recognition and treatment of specific manifestations of VHL disease can significantly reduce complications and improve quality of life. Patients usually undergo regular screening for retinal hemangioblastoma, CNS hemangioblastoma, clear cell renal cancer, and pheochromocytoma. Early surgical removal of these tumors is critical at the onset of symptoms.
"The drug Belzutifan for the treatment of VHL-related renal cell carcinoma is still under investigation."
Epidemiology
The incidence of VHL disease is approximately one in every 36,000 births. By the age of 65, the incidence rate exceeds 90%. The age at diagnosis of the disease ranges from infancy to 60 to 70 years old, with the average age at diagnosis being 26 years.
Historical background
VHL disease was first described by German ophthalmologist Eugene von Hipper in 1904. Arvid Lindau conducted further research into brain and spinal tumors in 1927, and by 1936, the term "Von Hippel-Lindau disease" began to be widely used.
Notable cases
Historically, some descendants of the McCoy family have been speculated to be carriers of VHL disease. According to an article published in The Associated Press, experts speculate that some members of the McCoy family produce too much adrenaline due to pheochromocytoma, which may also affect their moods and lead to conflicts. It shows the profound impact of VHL disease on life.
Have you ever thought about whether other rare diseases may inadvertently affect our daily lives and interpersonal relationships?
