Birt-Hogg-Dubé Syndrome

Birt-Hogg-Dubé syndrome (BHD syndrome)

What is BHD syndrome?

Birt-Hogg-Dubé syndrome (ORPHA:122, OMIM:135150) is a rare genetic condition that increases the risk of kidney cancer. A widely quoted figure states that 1 in 200,000 individuals will have BHD syndrome, but the conditions is generally considered to be underdiagnosed and the true prevalence is unclear. Persons with BHD syndrome can develop:

• Benign skin tumours: particularly on the face, neck and upper chest that appear around 20-30 years of age and become larger and more numerous over time.
• Pulmonary manifestations: persons with BHD syndrome are at an increased risk of spontaneous lung collapse and during their lifetime 25-50% will experience one or more incidences. The majority of individuals have multiple cyst in the lungs, which is not known to affect lung function.
• Benign and malign (cancerous) kidney tumours: persons with BHD syndrome are at an increased risk for kidney tumours and during their lifetime 15-30% of individuals will develop kidney cancer. Typically kidney tumours appear around age 40-50 years and are slow growing. Often they are bilateral and/or multifocal.

Dermatologists and doctors working in respiratory medicine have an important role in referring for genetic testing for BHD syndrome as the manifestations of BHD syndrome in skin and lung often are present before kidney cancer develops.

What causes BHD syndrome?

A definitive diagnosis of BHD syndrome is made by the detection of a pathogenic variant in one of an individual's two copies of the FLCN gene. In a subset of individuals a clinical diagnosis of BHD syndrome can be made based on clinical criteria even if a pathogenic FLCN variant is not identified.

How is BHD syndrome inherited?

BHD syndrome caused by FLCN pathogenic variants is inherited in an autosomal dominant way, which means that each child of an affected person has a 50% chance to inherit the FLCN variant and thereby BHD syndrome. Persons with BHD who are planning pregnancy should be offered referral to a medical genetics specialist for information and (reproductive) counselling. Pre-implantation genetic testing and/or invasive testing in pregnancy is technically possible.

What are the surveillance options for BHD syndrome?

According to the Clinical practice guidelines for the diagnosis, surveillance and management of people with Birt-Hogg-Dubé syndrome written by ERN GENTURIS:

• Kidney
  
  From age 20 years and life-long: Every 1-2 years renal imaging preferable by MRI with contrast, otherwise ultrasound.

• Lung
  
  Regular chest imaging or lung function testing is not indicated. At diagnosis a baseline CT of the chest can be considered.
  
  For specialised counselling regarding activities that may pose a risk for lung collapse (working as a pilot, flying unpressurised aircrafts, diving) referral to a pulmonologist familiar with BHD syndrome should be offered.

• Skin
  
  Referral to dermatological evaluation and treatment at diagnosis or on request.

 

More information Birt-Hogg-Dubé syndrome can be found on:

GeneReviews^® - Birt-Hogg-Dubé Syndrome
Orphanet: Birt-Hogg-Dubé syndrome

ERN GENTURIS documents

Clinical practice guidelines	ERN GENTURIS care pathway	ERN GENTURIS patient journey	ERN GENTURIS publications
Written by ERN GENTURIS
BHD syndrome guideline - Clinical practice guidelines for the diagnosis, surveillance and management of people with Birt-Hogg-Dubé syndrome	Care pathway - Birt-Hogg-Dubé syndrome (BHD syndrome)	Under development	Thematic Group 4: Other rare – predominantly malignant – genturis Birt-Hogg-Dubé syndrome

 

ERN GENTURIS education

ERN GENTURIS webinars - Thematic group 4: Other rare genturis

ERN GENTURIS webinars - General

 

ERN GENTURIS healthcare providers

A list of healthcare providers with expertise in Thematic Group 4: Other rare - predominantly malignant - genturis can be found here.

 

Patient associations for hereditary cancer syndromes

A non-exhaustive list of patient associations for genetic tumour risk syndromes in EU member states can be found here.