Von Hippel–Lindau disease (VHL) is a rare genetic condition which is inherited in an autosomal dominant pattern, with a frequency of approximately 1 in 36,000 live births. VHL is a hereditary cancer syndrome predisposing to a variety of malignant and benign neoplasms, most frequently retinal, cerebellar, and spinal hemangioblastoma, renal cell carcinoma (RCC), pheochromocytoma, and pancreatic tumors.

The disease results from a mutation in the Von Hippel-Lindau tumor suppresser gene (VHL gene) which located on the short arm of chromosome 3p25.3. The defect of VHL gene causes the loss of VHL protein activity results in an increased amount of HIF1a, and thus increased levels of angiogenic factors. In turn, this leads to unregulated blood vessel growth which is a predisposing factor for tumor formation leading to the disease. VHL may be diagnosed when one of its associated symptoms start to cause discomfort in the person suffering from the disease. Retinal and CNS hemangioblastomas are pathognomonic for the disease and their presence is a critical clue to diagnosis. Surgery is the mainstay of treatment for tumors that arise in patients with Von Hippel-Lindau disease. Current Medication for VHL-related cancers mainly targets the HIF pathway such as VEGF has recently been approved by FDA.

However, VHL is one of the single gene disorders that Superior A.R.T. can provide a preimplantation genetic diagnosis using polymerase chain reaction (PGD-PCR) to exclude the embryos affected with the disease. Therefore, only the disease-free embryos will be transferred to the uterus for further implantation. Commonly, PGD is used when a couple is aware of the possibility that their offspring will inherit a genetic disease. Where a couple are interested in PGD for detecting a single gene disorder, you can refer the patient with the following protocol. The fiirst process of PGD-PCR is a specific test kit preparation, at this stage the important information is required for test kit preparation are;

• Mutation reports of a couple and / or relative family members.
• Blood samples or DNA sample of a couple and relative family members

The procedure for test kit preparation:

• Clinician with a clinical geneticist or genetic counselor will arrange a consultation to a couple for the information of IVF/PGD-PCR treatment.
• A couple should be given an interview with a PGD scientist for family history and take family pedigree. The PGD scientist will assess a feasibility of test kit preparation from mutation report and indicate the appropriate blood samples to be collected from family members for test kit preparation.
• Collect blood samples from the couple and relevant family members. This should either be a) 3-4 ml blood collected in an EDTA tube or, b) blood collected onto a blood card. In some circumstances a buccal sample (mouth swab) may be collected.
• The test kit preparation will commence when PGD scientist has received all necessary mutation reports and blood samples. The test kit preparation normally takes 8-10 weeks to complete.
• * The patient should be informed that no stimulation can commence until a completed test is available at Superior A.R.T.*
• PGD scientist and nurse coordinator of Superior A.R.T. will report a completed test to clinician and patient. Following this a stimulation cycle can commence.
• Please notify nurse coordinator at Superior A.R.T. immediately when the stimulation cycle has started, in order to prepare case setting-up. Furthermore, you can directly bring your patient to start stimulation cycle at Superior A.R.T.
• If a patient comes through for any subsequent test cycles, PGD scientist at Superior A.R.T. should be notified immediately at least 2-3 weeks before or at start of any drug treatment. The scientist will review amount of test kit available. If insufficient then a new test kit will have to be made up and tested with no additional cost.

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