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Case Reports
. 2018 Mar 16;19(1):45.
doi: 10.1186/s12881-018-0558-0.

Delayed diagnosis of Birt-Hogg-Dubé syndrome due to marked intrafamilial clinical variability: a case report

E C Sattler  1 , O K Steinlein  2
Affiliations
Case Reports

Delayed diagnosis of Birt-Hogg-Dubé syndrome due to marked intrafamilial clinical variability: a case report

E C Sattler et al. BMC Med Genet. .

Abstract

Background: Birt-Hogg-Dubé syndrome is a genetic syndrome caused by mutations in the FLCN gene. The main symptoms are lung bullae and pneumothorax, benign and malignant kidney tumors, and facial fibrofolliculoma. The risk of pneumothorax is considerable between ages 20-40 years, but decreases markedly after this age range and first-time pneumothorax after age 50 years is rare. Fibrofolliculomas usually occur between ages 35 and 45 years, while the risk for kidney cancer increases steadily with age, starting in young adulthood. However, we demonstrate here that within the same family patients might develop symptoms significantly before or after the usual age range, obscuring the typical clinical pattern and delaying diagnosis.

Case presentation: The 43 year old index patient had a history of lung bullae and recurrent pneumothoraces starting 14 years earlier. His father (age 83 years) and one of the paternal uncles experienced their first pneumothorax unusually late after the age of 60 years. The uncle subsequently had four more pneumothoraces, and was diagnosed with kidney in his early 70s. Considerable differences in age of onset were also observed with regard to facial fibrofolliculomas that both paternal uncles developed very early around age 20 years, but which the father only started to show in his eighth decade. Birt-Hogg-Dubé syndrome was finally diagnosed when the index patient started to develop fibrofolliculomas within the typical age range.

Conclusions: The family described here illustrates that Birt-Hogg-Dubé syndrome can be difficult to recognize, if presenting with considerable intrafamilial clinical variability. With a life-time kidney cancer risk of about 14-35% the consequences of delayed diagnosis might be grave for the affected family members. The possibility of Birt-Hogg-Dubé syndrome should therefore be taken into consideration in apparently sporadic patients presenting with lung bullae and pneumothorax.

Keywords: Birt-Hogg-Dubé syndrom; FLCN; Kidney cancer; Lung bullae; Pneumothorax.

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Conflict of interest statement

Ethics approval and consent to participate

All research was conducted according to the declaration of Helsinki principles. The study has been approved of by the ethical committee/institutional review board (IRB) of the Medical Faculty, University Hospital Munich, under the project-number: 508/16UE.

Consent for publication

Written informed consent for the publication of medical data (including those of the index patients son), images, and medical history of family members was obtained from the index patient.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Pedigree of BDHS family. The index patient is marked by an arrow. Black symbol, BHDS confirmed by mutation analysis; grey symbols, clinical suspicion of BHDS
Fig. 2
Fig. 2
Chest computed tomography scan from the index patient. Bilateral pneumothorax (large arrows) and lung bullae (small arrows) are indicated. The pneumothorax is mostly localized in the basal parts of the chest cavity due to previous pleurodesis treatment
Fig. 3
Fig. 3
Sequence electropherogram demonstrating the mutation c.1285dupC (p.His429ProfsX27) within exon 11. The position of the duplicated cytosine is marked by an arrow
See this image and copyright information in PMC

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