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Test ID: FLCNZ Birt-Hogg-Dube Syndrome, Full Gene Analysis

Useful For

Genetic diagnosis of Birt-Hogg-Dube syndrome for clinical management, risk assessment for related clinical symptoms, and genetic counseling for family members

Method Name

Polymerase Chain Reaction (PCR) Amplification/DNA Sequencing and Deletion Detection by Multiplex Ligation-Dependent Probe Amplification (MLPA)

Reporting Name

FLCN Gene, Full Gene Analysis

Specimen Type

Varies


Specimen Required


Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Additional Information: Specimen preferred to arrive within 96 hours of collection.

Specimen Stability Information: Ambient (preferred)/Refrigerated


Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time
Varies Ambient (preferred)
  Frozen 
  Refrigerated 

Clinical Information

The clinical characteristics of Birt-Hogg-Dube syndrome (BHDS) include cutaneous manifestations (fibrofolliculomas, trichodiscomas/angiofibromas, perifollicular fibromas, and acrochordons), pulmonary cysts/history of pneumothorax, and various types of renal tumors. Skin lesions typically appear during the third and fourth decades of life and typically increase in size and number with age. Lung cysts are mostly bilateral and multifocal; most individuals are asymptomatic but have a high risk for spontaneous pneumothorax. Individuals with BHDS have an increased risk of renal tumors that are typically bilateral and multifocal and usually slow growing; median age of tumor diagnosis is 48 years with a range from 31 to 71 years. Some families have renal tumor and/or autosomal dominant spontaneous pneumothorax without cutaneous manifestations.

 

BHDS is inherited in an autosomal dominant manner and penetrance is considered to be very high. FLCN (also known as folliculin or BHD) is the only gene known to be associated with BHDS. Sequence analysis detects mutations in FLCN in 88% of affected individuals. Recent studies have reported that multi-exonic deletions can account for up to 5% to 10% of additional mutations.(2, 3)

 

Molecular genetic testing is indicated in all individuals known to have or suspected of having BHDS, including individuals with one of the following:

-Five or more facial or truncal papules with at least 1 histologically confirmed fibrofolliculoma, with or without a family history of BHDS

-Facial papules histologically confirmed to be angiofibroma in an individual who does not fit the clinical criteria of tuberous sclerosis complex (TSC) or multiple endocrine neoplasia type 1 (MEN1)

-Multiple and bilateral chromophobe, oncocytic, and/or hybrid renal tumors

-A single oncocytic, chromophobe, or oncocytic hybrid renal tumor and a family history of renal cancer with any of these renal cell tumor family history of renal cancer with any of the above renal cell tumor types

-A family history of autosomal dominant primary spontaneous pneumothorax without a history of smoking or chronic obstructive pulmonary disease (COPD)

 

In the absence of an increased risk of developing childhood malignancy, the American Society of Clinical Oncology (ASCO) recommends delaying genetic testing in at-risk individuals until they reach age 18 years and are able to make informed decisions regarding genetic testing.

Reference Values

An interpretive report will be provided.

Interpretation

All detected alterations will be evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(1) Variants will be classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Clinical Reference

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424

2. Benhammou JN, Vocke CD, Santani A, et al: Identification of intragenic deletions and duplication in the FLCN gene in Birt-Hogg-Dube syndrome. Genes Chromosomes Cancer 2011;50:466-477

3. Houweling AC, Gijezen LM, Joneker MA, et al: Renal cancer and pneumothorax risk in Birt-Hogg-Dube syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families. Br J Cancer 2011;105:1912-1919

4. Schmidt LS, Nickerson ML, Warren MB, et al: Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dube Syndrome. Am J Hum Genet 2005;76:1023-1033

Day(s) and Time(s) Performed

Performed weekly, Varies

Analytic Time

14 days

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81479-Unlisted molecular pathology procedure code

LOINC Code Information

Test ID Test Order Name Order LOINC Value
FLCNZ FLCN Gene, Full Gene Analysis In Process

 

Result ID Test Result Name Result LOINC Value
53908 Result Summary 50397-9
53909 Result In Process
53910 Interpretation In Process
53911 Additional Information 48767-8
53912 Specimen In Process
53913 Source 31208-2
53914 Released By No LOINC Needed

Forms

1. Molecular Genetics: Inherited Cancer Syndromes Patient Information (T519) in Special Instructions

2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-inherited-molecular