Short summary

Birt-Hogg-Dubé syndrome (BHD) is a rare genetic disease which involves lungs, skin and kidneys. This observational study aims to describe characteristics of patients with Birt-Hogg-Dubé syndrome followed in CAKS in order to examine how pulmonary manifestations of BHD develop over time.

Rationale

Birt-Hogg-Dubé syndrome (BHD) is a rare genetic disease which is characterized by growth of cutaneous hamartomas, multiple lung cyst which can lead to spontaneous pneumothorax, and renal cysts that might transform into renal cell cancer (RCC).

Currently, the diagnosis and follow-up of BHD in the Region of Southern Denmark is handled at Odense University Hospital (OUH) in clinical collaboration between the departments of respiratory medicine, clinical genetics, urology, dermatology, and radiology through the "Center for Arvelige og Komplekse Sygdomme (CAKS)". The Department of Respiratory Medicine is responsible for each individual patient course. The Danish societies for respiratory medicine, genetics and dermatology have collaborated on a national guideline for obtaining diagnosis and follow-up for BHD. Follow-up is conducted every two years at the department of respiratory medicine, which includes respiratory function testing and MRI scan of the kidneys.

Through CAKS' follow-up experience of BHD patients, the impression alongside with other Danish BHD-centres is that lung cysts associated with BHD exhibit very slow development and are only sparsely observed on lung physiological tests and thoracic imaging. The need for prolonged follow-up for several years may therefore not be necessary from a pulmonary perspective. However, in Denmark we have no available long-term follow-up data to explore this assertion.

As such, we hypothesize that the current BHD guideline concerning respiratory examinations may lead to thoracic imaging and pulmonary function tests, which do not lead to further respiratory interventions. As a potential consequence, the frequency and time for follow-up may be reduced or shifted to solely urological follow-up regarding continuous risk monitoring for RCC.

Description of the cohort

The study population cover BHD patients registered in CAKS at OUH who are verified with positive FLCN gene test compatible with BHD in the period 02.10.2018 - 01.02.2023. During this observation period, the index date was defined as the date of BHD diagnosis (ICD-10 code: DQ878K).

At present (Oct. 2022) 98 patients are registered with BHD in CAKS.

Data and biological material

Patient information which are estimated to be included by medical records review: Genetic mutation, smoking and abuse, comorbidities, respiratory function, HRCT-thorax findings, MR-kidneys findings, bloodwork, impact on lungs (spontaneous pneumothorax, pleurodesis, bullectomy, histology, pathology etc), impact on skin (skin lesions, treatment, histology, pathology etc), impact on kidneys (tumors/cyst, surgery, biopsy, histology, pathology etc).

Collaborating researchers and departments

Department of Respiratory Medicine, Odense University Hospital

• Associate Professor, Jesper Rømhild Davidsen, Specialist Chief Consultant, MD, PhD
• Casper Falster, MD, PhD-student

Department of Radiology, Odense University Hospital

• Professor Ole Grauman, MD, PhD