• Test code: 01720
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit

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.

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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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

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