1. Case description
A 50-year-old woman presented with multiple cutaneous lesions that had been present for many years (Figure 1a and 1b) similar to other family members. Her past history was significant for seronegative arthritis, juvenile rheumatoid arthritis, iron deficiency anaemia, menorrhagia and cholecystectomy. She had never smoked. Family history was significant for thyroid cancer in her mother. Computed Tomography (CT) scan of her thorax demonstrated multiple intraparenchymal pulmonary cysts and subpleural bullae bilaterally (Figure 1c and 1d). A magnetic resonance imaging (MRI) abdomen was done to screen for renal tumours but did not reveal any abnormalities.
2. What is the diagnosis?
2.1 Diagnosis
2.1.1 Birt-Hogg-Dube syndrome
Genetic testing revealed a heterozygous variant FLCN mutation associated with Birt-Hogg-Dube Syndrome (BHDS). BHDS is a rare, autosomal-dominant disorder, described and genetically confirmed in around 200 families, characterized by the development of cutaneous lesions, renal tumours and pulmonary cysts [
[1]
]. The gene responsible for BHDS is located on chromosome 17p11.2 [[2]
]. Germline mutations in this gene result in loss of function of folliculin (FLCN); which is thought to have a tumor-suppressor role [[2]
].Dermatological manifestations of BHDS include fibrofolliculomas, trichodiscomas, perifollicular fibromas and acrochordons [
[3]
]. Clinical hallmarks are fibrofolliculomas, bilateral pulmonary cysts and repeated pneumothoraces [[1]
]. Pulmonary cysts manifest as rounded lesions with well-defined interface with normal lung parenchyma [[1]
]. Renal cancers are the most serious complication of BHDS with a 7-fold increased risk compared to the general population [[1]
]. Multiple other benign and malignant tumours have been associated in patients with BHDS [[1]
].Diagnosis should be suspected in young patients with the above clinical hallmarks [
[1]
]. Management of BHDS should be with a multidisciplinary team, including a Genetics service. Management includes treatment/prevention of pneumothoraces and screening for renal tumours (with MRI or ultrasonography) [[1]
]. Although BHDS is a rare condition, increased awareness of the manifestations and imaging findings are crucial for management of complications and early detection of malignancies.Declaration of Competing interest
All of the case authors declare no financial or other potential conflicts of interest.
References
- Birt-Hogg-Dubé syndrome: state-of-the-art review with emphasis on pulmonary involvement.Respir Med. 2015; 109: 289-296
- Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome.Cancer Cell. 2002; 2: 157-164
- Birt-Hogg-Dubé syndrome: a review of dermatological manifestations and other symptoms.Am J Clin Dermatol. 2018; 19: 87-101
Article info
Publication history
Published online: May 19, 2020
Accepted:
April 20,
2020
Received:
March 1,
2020
Identification
Copyright
© 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
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