Von hippel-lindau syndrome

Inheritance

How is von Hippel-Lindau syndrome inherited?

Von Hippel-Lindau syndrome (VHL) is inherited in autosomal dominant manner. This is one way a disorder or trait can be passed down through a family. The first word, "autosomal," means on a chromosome that both males and females carry. Therefore, von Hippel-Lindau syndrome can affect either gender. The second word, "dominant," means a gene change in one copy of a person's VHL gene is enough for them to develop the disease. We have two copies of every gene - one from our mother and one from our father - for a dominant condition, only one of them needs to have the problem. This means that if a parent carries an altered VHL gene, they have a 50% chance to pass the affected gene to each of their offspring, regardless of gender. This also means that there is a 50% chance that an affected parent would not pass this on to their children.

In about 20% of people, there is no previous history of VHL syndrome in the family. The altered VHL gene occurs randomly, most likely after fertilization. This is also called a de novo mutation. The altered VHL gene in the child can be passed on as an autosomal dominant trait. In families with a child with a de novo mutation, the likelihood of having another child with VHL syndrome is extremely low.

VHL syndrome is different from many other autosomal dominant disorders. While most disorders that follow this pattern inheritance only require one altered gene, people with VHL syndrome have both their VHL genes changed. While one altered gene may be inherited (germline mutation), the other VHL gene must be altered at some point after conception (somatic mutation). There are a few different ways this might happen. Doctors call this the "two-hit theory".

If you have a family member with VHL syndrome or you would like to know more about the genetics of the disorder, genetic counselors can be found in a particular area by searching on the National Society of Genetic Counselor's website

References
  • Von Hippel-Lindau syndrome. Genetics Home Reference website. Accessed September 8, 2016. https://ghr.nlm.nih.gov/condition/von-hippel-lindau-syndrome
  • Frantzen C, Klasson TD, Links TP, Giles RH. Von Hippel-Lindau syndrome. GeneReviews website. Accessed September 8, 2016. http://www.ncbi.nlm.nih.gov/books/NBK1463/
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How likely is von Hippel-Lindau syndrome to be passed on in a family?

What does it mean to have inherited a "variant" or "variant of unknown significance" in the gene for von Hippel-Lindau syndrome?

My child has Von Hippel Lindau. Will others in the family have it?

How likely is von Hippel-Lindau syndrome to be passed on in a family?

We each get two copies of most of our genes from our parents. One copy comes from our mother and the other copy comes from our father. In von Hippel-Lindau (VHL) syndrome, only one parent must pass along a nonworking copy of the VHL gene to their child for them to have an increased risk of developing tumors and cysts. Because of this, VHL syndrome is inherited in what is called an autosomal dominant pattern. This means a person only needs one altered VHL gene to have the disorder. In most families with VHL syndrome, one parent will have an altered VHL gene, which causes their disease. So, each of their children will have a 50% chance of inheriting that mutation and developing the disease. Almost all individuals who have a pathogenic variant in VHL are symptomatic by age 65 years.

In about 20% of families, a child will develop VHL syndrome and be the first person in the family with the disorder. This occurs because of a de novo mutation, which means that the altered VHL gene occurs randomly, most likely after fertilization. The child who carries the altered gene can pass on the alteration in an autosomal dominant manner. In families with a child with a de novo mutation, the likelihood of having another child with VHL syndrome is extremely low.

To learn more about the inheritance of VHL, consult with a genetic counselor. Genetic counselors can be found in a particular area by searching on the National Society of Genetic Counselor's website

References
  • Von Hippel-Lindau syndrome. Genetics Home Reference website. Accessed September 8, 2016. https://ghr.nlm.nih.gov/condition/von-hippel-lindau-syndrome
  • Frantzen C, Klasson TD, Links TP, Giles RH. Von Hippel-Lindau syndrome. GeneReviews website. Accessed September 8, 2016. http://www.ncbi.nlm.nih.gov/books/NBK1463/
What does it mean to have inherited a "variant" or "variant of unknown significance" in the gene for von Hippel-Lindau syndrome?

Von Hippel-Lindau (VHL) syndrome is caused by a disease causing change (variant) in the VHL gene. However, not all changes or mutations in a gene necessarily cause disease. If a change is known to cause VHL syndrome, it is known as a pathogenic or disease-causing variant. Most people with a pathogenic variant in the VHL gene eventually develop symptoms by the age of 65. Sometimes gene changes are found and scientists are unsure what it means, either because it has not been found before or has only been found in a few people. This is known as a variant of unknown significance. If you have a variant of unknown significance in the VHL gene, talk to your doctor about further testing that may help find out whether the gene change is pathogenic or not. A genetic counselor may also be able to help you review your test results. To find a genetic counselor near you who can discuss testing and results, search on the National Society of Genetic Counselor's website.

References
  • Frantzen C, Klasson TD, Links TP, Giles RH. Von Hippel-Lindau syndrome. GeneReviews website. Accessed September 8, 2016. http://www.ncbi.nlm.nih.gov/books/NBK1463/
My child has Von Hippel Lindau. Will others in the family have it?

Because Von Hippel Lindau (VHL) is inherited in an autosomal dominant inheritance pattern, it means that every first degree relative of an affected individual has a 50% chance of also having it. First degree relatives are siblings, children, and parents. Second degree relatives are at 25% risk until the risk is modified based on results in closer relatives. In a specific example, let's say 27-year-old Andrea has been diagnosed with VHL and a specific disease causing gene change has been identified. Andrea has 3 children. EACH of her children has an individual 50% chance to also have it. Andrea has 2 siblings: one brother and one sister. EACH of her siblings has an individual 50% chance to also have it. Andrea's mother has testing and is negative. This means that Andrea's mothers side of the family (her siblings, her parents, etc.) is not at increased risk to be affected by VHL do NOT need to pursue further testing. Andrea's father has testing and is positive. Each of Andrea's father's siblings should have testing as well, because they now have an individual 50% chance of being positive as well.

To find a genetic counselor near you who can discuss the inheritance and testing of VHL, search on the National Society of Genetic Counselor's website.

References
  • Accessed on October 20, 2019: GeneReviews (https://www.ncbi.nlm.nih.gov/books/NBK1463/)

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