Folliculin Gene-negative Birt-Hogg-Dube Syndrome: a Case Report

Overview

Journal Ann Med Surg (Lond)

Publisher Wolters Kluwer

Specialty Medical Education

Date 2024 Feb 9

PMID 38333273

Authors

Mohammad F Dwikat

Jehad Azar

Rama Rabayah

Ruba Salameh

Fatima Abdeljaleel

Waseem Almadhoun

Alaa Ayyad

Farah Ibraik

Omar Safarini

Affiliations

Soon will be listed here.

Abstract

Introduction And Importance: Birt-Hogg-Dube (BHD) is a rare genetic disorder that results from a mutation in the folliculin (FLCN) gene. Manifestations include pulmonary cysts, fibrofolliculomas, renal tumors, and pneumothoraces. Genetic testing can be used to confirm the diagnosis when suspected. BHD syndrome is diagnosed in patients with negative FLCN gene results using diagnostic criteria.

Case Presentation: A male in his 20s presented with recurrent pneumothoraces. A physical examination revealed bumps on his face and upper body. A chest computed tomography scan revealed cystic lesions. Blood tests, ESR, and CRP levels were unremarkable. Punch skin biopsy revealed fibrofolliculomas. Genetic testing for the FLCN mutation returned negative. His history, physical exam, imaging, and histopathology suggested BHD syndrome despite having a negative family history and genetic analysis. Eventually, the patient was diagnosed with FLCN gene-negative BHD syndrome.

Clinical Discussion: More than a hundred families have been identified to have BHD worldwide. There are a few cases in the literature describing patients phenotypically presenting with BHD despite having a negative genetic analysis. One study in Japan found 16 out of 157 individuals having a clinical presentation of BHD with no mutations. Also, decreased expression of the FLCN mRNA may lead to BHD.

Conclusion: BHD syndrome can present with a negative FLCN gene mutation; however, patients must meet the known diagnostic criteria such as criteria made by Menko ., Gupta ., and Schmidt . in order to have a diagnosis of BHD syndrome. Also, a qualitative decrease of FLCN with the absence of mutations may also lead to BHD.

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