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Birt-Hogg-Dube Syndrome via the FLCN Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
FLCN 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8409FLCN81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Melanie Jones, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Birt-Hogg-Dubé syndrome (BHDS) includes cutaneous manifestations, such as fibrofolliculomas (yellowish dome-shaped papules), trichodiscomas (multiple small papules), and acrochordons (skin tags). Skin features typically appear in the third to fourth decade of life and continually grow in size and number with age. BHDS is also characterized by pulmonary cysts/history of pneumothorax, and various types of renal tumors. The renal tumors that develop are usually bilateral and multifocal, and slow growing (Toro. GeneReviews. 2014). Tumor types include renal oncocytoma, chromophobe renal cell carcinoma, oncocytic hybrid tumor, and a minority of clear cell renal cell carcinoma. The median diagnosis of renal tumors is 48 years of age (range 31-71 years) (Schmidt et al. Am J Hum Genet 76:1023–33, 2005). Some families have renal tumor and/or autosomal dominant spontaneous pneumothorax without cutaneous manifestations. Early diagnosis is important for intervention and improving patient morbidity, since mutations in the FLCN gene may be associated with other cancers (Palmirotta et al. Anticancer Research 30: 751-758 2010; Toro et al. J Med Genet 45:321–331, 2008).


BHDS is inherited in an autosomal dominant pattern with high penetrance and is caused by mutations in the FLCN gene. The proportion of de novo versus inherited mutations in FLCN is currently unknown. FLCN encodes the folliculin protein, which is highly expressed in skin, type 1 pneumocytes, and distal nephrons of the kidney (Toro. GeneReviews. 2014). Its exact function is unknown, although it may act downstream of rapamycin (mTOR), adenosine monophosphate-activated protein kinase (AMPK), and have a role in the modulation of energy/nutrient sensing and signaling pathways (Hartnan Oncogene 28(13): 1594-1604, 2009). It has also been suggested to have a role in tumor suppression from the observation that germline mutations in FLCN cause renal tumors, and the presence of somatic mutations and loss of heterozygosity in tumors tissues. The most frequent causative mutation occurs within a polycytosine C8 tract of exon 11 . This mutation probably occurs due to DNA polymerase slippage resulting in gains or losses of repeat units leading to truncated folliculin. Other causative mutations are located throughout the FLCN gene (Palmirotta et al. Anticancer Research 30: 751-758 2010). These include missense, nonsense, splicing, small and large insertions and deletions (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PG-Select

FLCN causative mutations will be detected in approximately 88% of individuals with BHDS by sequencing. Almost half of the individuals with BHDS will have a deletion (c.1285delC) or duplication (c.1285dupC) of a C nucleotide in the polycytosine tract in exon 11 (Toro. 2014. GeneReviews). Deletions and duplications are reported in 3-5% of individuals with Birt-Hogg-Dubé Syndrome (Toro. 2014. GeneReviews).

Testing Strategy

This test provides full coverage of all coding exons of the FLCN gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Molecular genetic testing is suggested for individuals known to have or suspected of having BHDS, including individuals with either one major or two minors findings as listed below (Menko et al. Lancet 10:1199, 2009):

Major criteria

• At least five fibrofolliculomas or trichodiscomas (at least one histologically confirmed)

Minor criteria

• Multiple lung cysts: bilateral basally located lung cysts with no other apparent cause, with or without spontaneous primary pneumothorax

• Renal cancer: early onset (<50 years) or multifocal or bilateral renal cancer, or renal cancer of mixed chromophobe and oncocytic histology

• A first-degree relative with BHDS


Official Gene Symbol OMIM ID
FLCN 607273
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Hereditary Leiomyomatosis and Renal Cell Cancer or Fumarase Deficiency via the FH Gene
Interstitial Lung Disease Panel
Renal Cancer Panel


  • Hartnan et al. 2008. The role of the Birt-Hogg-Dubé protein in mTOR activation and renal tumorigenesis. Oncogene 28(13): 1594-1604. PubMed ID: 19234517
  • Human Gene Mutation Database (Bio-base).
  • Menko et al. (2009) "Birt-Hogg-Dubé syndrome: diagnosis and management."  Lancet 10:1199. PubMed ID: 19959076
  • Palmirotta et al. (2010) "Association between Birt Hogg Dube syndrome and cancer predisposition." Anticancer Research 30: 751-758. PubMed ID: 20392993
  • Schmidt et al. (2005) "Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dubé syndrome." Am J Hum Genet 76:1023–33,. PubMed ID: 15852235
  • Toro et al. (2008) "BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dubé syndrome: a new series of 50 families and a review of published reports." J Med Genet 45:321–331. PubMed ID: 18234728
  • Toro JR. 2014. Birt-Hogg-Dubé Syndrome. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle,. PubMed ID: 20301695


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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