BHD Toolkit: Getting your Diagnosis

We know that receiving a diagnosis for a rare condition can sometimes be a confusing and overwhelming process. Following on from our first BHD Toolkit, we spoke to Dr Derek Lim, Consultant Clinical Geneticist at Birmingham Women’s and Children’s Hospital, UK to help understand what happens at an appointment with a clinical geneticist. Although this pathway is specific to the UK, we hope this provides a general idea of what to expect when you see a clinical geneticist.

How do you get an appointment with a clinical geneticist?

Dr Lim described the three main routes by which individuals are referred to his monthly BHD genetics clinic.

  1. Individuals who have already had a positive diagnostic genetic test for BHD and are referred to discuss the diagnosis, management, surveillance and genetic counselling.
  2. Individuals who are referred to him for a possible diagnosis of BHD (i.e. they have not yet had a genetic test).
  3. Individuals who have a family member who has been diagnosed with BHD.

What happens during your appointment?

What happens during the appointment will depend on whether an individual has already had a genetic test for BHD.

If this is the case (i.e. route number 1), then the genetic test result is explained to them along with an explanation of BHD including the different manifestations and recommended management and surveillance strategies. Dr Lim explained he would also take a thorough family history, examine individuals for skin bumps and refer them for a CT scan of their lungs if they have not already had one and arrange a scan of the kidneys.

If an individual has not had a genetic test for folliculin (FLCN) and are being referred for a possible BHD diagnosis (i.e. route number 2), then Dr Lim provides an explanation of BHD and offers a skin examination to check for skin bumps. If there is sufficient evidence to suspect BHD, a genetic test to look for FLCN variants will be offered. In this instance, the results are often relayed to the individual in a letter as BHD and the management of the condition have already been explained. There is, however, less opportunity to offer further explanation of the sequencing result itself but a follow-up consultation can be arranged if required.

If an individual has been referred to the clinic because a family member has been diagnosed with BHD (i.e. route number 3), a genetic test for the specific variant identified in the family is offered in the following cases: If there are clinical signs of BHD (e.g. skin bumps, or history of pneumothorax/lung cysts or kidney tumours) – this is called a “diagnostic test” or, if there are no clinical signs  a “pre-symptomatic test” is offered. Sometimes it may be appropriate to test another family member first (e.g. a parent of the individual being seen in clinic).

Why is it important to know the specific FLCN variants?

There are several reasons why knowing the specific variant an affected individual has is important. Firstly, from a clinical perspective, the test required for other family members is simpler and cheaper than having to test for variants in the entire FLCN gene, or potentially panel of genes. Dr Lim likened this to finding a spelling mistake in a book. It is a much easier task to find the spelling mistake once you have been able to narrow down the page, paragraph and line the spelling mistake is in. Secondly, knowing the specific variant is also useful to predict the effect of the mutation on the function of the FLCN protein. In turn, this allows the prediction of whether the FLCN variant will be pathogenic, in other words, how likely it is to develop any symptoms associated with BHD. Finally, it is useful for scientists to know what different variants exist so that research can be done to identify if there are any correlations between genotype (the genetic code) and phenotype (the symptoms of BHD), e.g. whether having a particular FLCN variant increases the risk of developing kidney cancer.

What are some of the common questions asked during an appointment?

During appointments where an individual is discussing their diagnosis, a lot of information can be given in a short space of time, and it may be difficult to think of questions that might be relevant.  We asked Dr Lim the most common questions he is asked in his clinic and here are his top 3:

  1. When should my children be tested?
    In the UK, monitoring of the kidneys (preferably a MRI scan) begins at 18 years of age and so appointments to discuss genetic testing are usually made between the ages of 16 and 18.
  2. How often do I need lung scans?
    In the UK, regular monitoring of the lungs isn’t recommended due to repeated radiation exposure through CT imaging. A CT scan is recommended at diagnosis if the individual has not already had one. Importantly, individuals are made aware of the symptoms of a pneumothorax and what to do if an individual experiences one.
  3. Will I get skin bumps and what are the available treatments?
    Although skin bumps are the most common manifestation of BHD, it is not guaranteed an individual will develop them Some individuals may only have a few whereas others may have hundreds. There are treatments available, however they do not prevent the formation of new skin bumps. You can find a list of possible treatments here.

We are extremely thankful to Dr Lim for providing us with his insight into what happens during a clinical genetics appointment. If you have any further questions about genetic testing for BHD please get in touch with us by email and we will be happy to help. Our next toolkit will delve deeper into the actual sequencing results to help you understand what they mean!

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