Prevalance of Birt-Hogg-Dubé syndrome among patients with (hereditary) spontaneous pneumothorax

Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant disease,
characterized by skin fibrofolliculomas, renal cancer, multiple lung cysts and
pneumothorax.
The BHD-Syndrome is caused by a mutation in the FLCN-gene, which is localised
on chromosome 17, and encodes for the protein folliculin.
In over 80 percent of the patients with clinical BHD syndrome, a pathogenic
FLCN mutation can be demonstrated. The clinical expression is variable:
patients may present with skin lesions, renal cancer or pneumothorax.
The skin signs consist of are 1-5 mm multiple white or skin-coloured papules,
in particular on the face, neck and torso. These fibrofolliculomas are benign
lesions originating from hair follicles. Treatment is cosmetic with laser
techniques .
The observed prevalence of renal cancer in BHD-patients has varied between 6
and 35%. Renal cancer in BHD is diagnosed at a relative young age and is often
multifocal and/ or bilateral. For early detection and treatment FLCN mutation
carriers are advised to undergo yearly renal ultrasound.
Lung cysts have been found in 80-90% of patients with BHD syndrome, more often
localised basally than in the apical regions. These lung cysts may cause
pneumothorax. In about 25% of FLCN mutation carriers pneumothorax before the
age of 50 has been observed. Recurrent pneumothorax is common.
.
Familial occurrence of pneumothorax is found in about 10% the patients with
spontaneous pneumothorax.
As stated above, the clinical expression of BHD is variable. BHD families with
*pneumothorax-only*have been observed without skin or renal lesions.
Based on recent studies, 15-25% of the familial pneumothorax is due to an
underlying FLCN mutation.

To assess the prevalence of BHD among patients with spontaneous sporadic and
familial pneumothorax.

Based on the results of our pilotstudy in VUmc, in which 3 out of 40 tested
patients had a pathological FLCN mutation, we decided to extend the study to a
second center; Rijnstate ziekenhuis Arnhem.
In this hospital was performed retrospective research in february 2014. We
searched in 750 patientfiles. Totally, we included 450 PSP patients who were
admitted in the pulmonary ward between 2003 and 2013. In the dossiers we
searched for medical history, pneumothorax side and recurrence, diagnostic
imaging, treatment, co-morbidity, complications of treatment,
skinabnormalities, kidneydisease, smoking behaviour, medication, and familial
incidence of pneumothorax and other diseases.
This group of patients will recieve a lettre with explanation of the research
and a questionary in which we ask them their medical status, co-morbidty,
pneumothorax (number and side), smkoing behaviour, use of drugs, familial
incidence of pneumothorax and other diseases.

Patients who have given consent to be included in further research, will be
invited to come to our outpatient clinic for one visit. As above discribed, it
concernes a onetime non-invasive examination, the patient will sign a consent
form. The participation will include a low dose CT scan (2mSv) and the 2 venous
blood samples (2x8ml).