Invitae Birt-Hogg-Dubé Syndrome Test


Test description

This test analyzes the FLCN gene. Pathogenic variants in this gene are associated with Birt-Hogg-Dubé syndrome (BHD). Features of BHD include benign cutaneous lesions, pulmonary cysts, and renal cancer.

Many of the features of BHD are nonspecific, can occur as isolated findings, and can present as features of other conditions. Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

Order test

Primary panel (1 gene)


Birt-Hogg-Dubé syndrome

Birt-Hogg-Dubé (BHD) is a rare disorder that affects the skin, lungs, and kidneys. The condition is also associated with an increased risk of certain tumors.

The characteristic skin findings in BHD typically present in the third and fourth decades of life. These lesions include benign cutaneous tumors such as fibrofolliculomas, trichodiscomas, angiofibromas, perifollicular fibromas, and skin tags (acrochordons), most often found on the face, neck, and upper chest. These growths typically increase in size and number over time.
The lungs and kidneys are also often affected. Non-cancerous pulmonary cysts may develop that can lead to spontaneous pneumothorax. Additionally, there is an increased risk of adult-onset benign and malignant kidney tumors, most often hybrid oncocytic renal cell carcinoma, oncocytoma, chromophobe renal cell carcinoma, and, less commonly, clear cell renal carcinoma.

Other types of cancer have also been reported in affected individuals, but it is unclear whether these tumors are actually a feature of Birt-Hogg-Dubé syndrome. The signs and symptoms are highly variable from person to person, even among family members. In some cases, affected individuals may present with the typical pulmonary and/or renal findings in the absence of the characteristic skin features.

While it appears that most individuals who have a pathogenic variant in the FLCN gene will develop symptoms of the condition, the specific penetrance is unknown. The risk for renal cancer is approximately 16%. There is also limited evidence to suggest there may be an increased risk of colon cancer.

FLCN sequencing identifies pathogenic variants in 88% of individuals with BHD. An additional 3%-5% have partial or whole-gene deletions. Approximately 7%-9% of affected individuals who meet the clinical diagnostic criteria for BHD will not have an identifiable FLCN pathogenic variant.

In many cases, BHD is inherited from a parent in an autosomal dominant pattern; however, an unknown percentage of BHD cases occurs as the result of a spontaneous de novo mutation.

Birt-Hogg-Dube syndrome is considered to be rare, but the exact prevalence is unknown. Because the condition is highly variable, it may be underdiagnosed.

BHDS may be suspected in individuals with a personal and/or family history of the following:

  • spontaneous pneumothorax
  • pulmonary cysts
  • multiple papular skin lesions
  • renal cysts and/or renal cancer

Clinical diagnostic criteria have also been proposed:

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
FLCN NM_144997.5