BHD at Rare Diseases International Policy Event

The Myrovlytis Trust/BHD Foundation attended the Rare Diseases International Policy Event “The Right to Health: The Rare Disease Perspective” at the beginning of February in Geneva.

You can check the livestream recordings of the 3 panels, the presentations, the photos and all other relevant information about the meeting here.

New BHD clinical trial on ClinicalTrials.gov

An observational study  – Assessment of Safery of Air Travel in Patients with BHD Syndrome – aims to assess the safety of air travel in patients with BHD syndrome via a questionnaire. Secondary aims of this study include further characterisation of the clinical aspects of disease and to establish a contact registry for these patients, in order to facilitate future studies.

Further details about the study, including access to the study questionnaire, are provided in the link below:

https://redcap.research.cchmc.org/surveys/?s=oNTxfZ9gqz

Four new BHD case studies

Li et al., 2017 report two Chinese BHD patients with novel FLCN mutations (c.946-947delAG and c.770-772delCCT), a 54-year-old man and a 37-year-old man. Both had RCC and spontaneous pneumothorax without fibrofolliculomas and spontaneous pneumothorax on their family history. The incidence of fibrofolliculomas may be lower among Asian BHD patients compared with the higher incidence reported among patients from the United States and Europe.  In patients with RCC and pulmonary cysts but without cutaneous lesions, screening for mutations in the FLCN gene should be performed, especially for those with a family history of RCC or pulmonary cysts.

Castellucci et al., 2016 report the case of a patient with seven kidney tumours discovered after ultrasound performed for other reasons. Tumours were classified as multifocal type chromophobe renal cell carcinoma and clear cell. After 1 month, the patient was readmitted for spontaneous pneumothorax. Genome analysis highlighted the FLCN mutation c. 1379_1380. Currently, the patient is under close follow-up. After 1 year, the chest computed tomography (CT) confirmed the presence of minute air bubbles scattered on both sides of the lungs.

Wiyono et al., 2016 present the case of a 51-year-old Indonesian female presenting with recurrent spontaneous pneumothorax, multiple cysts in both lungs, and a renal cyst. Her family history revealed that her mother had a history of renal tumour. Genetic testing detected a pathogenic FLCN mutation c.601C > T.

Monserrate et al., 2016 present the case of a 54-year-old male with a past medical history of spontaneous pneumothorax. Family history was significant for emphysema and pneumothorax. A chest CT confirmed diagnosis of pneumothorax, with severe bilateral bullous changes. Patient underwent bronchoscopy with placement of intra bronchial valves (IBVs). Because of persistent cough, IBVs were removed 3 weeks after discharge. During the follow-up, the patient achieved complete resolution of respiratory symptoms. Genetic testing revealed a FLCN gene mutation confirming BHD syndrome. This is the first case report in the literature on the use of IBV for the management of pneumothorax in BHD. IBVs are emerging as a new minimally invasive therapy to be considered in patients who develop spontaneous pneumothoraces with persistent air leaks and underlying lung disease leading to fewer surgical interventions and pleurodesis.

Case studies are freely available to download in the BHD Article Library: Clinical Research.

New Japanese case study and clinical features of Japanese studies

Tanegashima et al., 2016 report the case of a 54-year-old Japanese man presenting with skin-coloured papules on his face and neck. Pathological examination revealed the presence of fibrofolliculoma. The patient’s sister was previously diagnosed with BHD Syndrome with multiple pulmonary cysts and renal cell carcinomas but no skin symptoms. CT exams revealed the presence of multiple pulmonary cysts and a renal tumor diagnosed as a chromophobe renal cell carcinoma on the male patient. Genetic analysis revealed a germ line mutation of FLCN in exon 11 (c.1285dupC), the same as his sister. He was diagnosed with BHD with all three symptoms. It is possible that the frequency of each clinical BHD symptom differs with race and gender. The authors analyzed the symptoms of 68 Japanese BHD cases from the available publications from 1990 to 2015. Pulmonary cysts and renal cell carcinomas were found in 82.4% and 29.4% of Japanese patients, and their prevalence was similar to that in Caucasians. However, significantly fewer skin lesions were found in Japanese than in Caucasians (43.1% vs 90.0%). In addition, Japanese men had a significantly higher prevalence of skin lesions than women (66.7% vs 31.3%).

First case of BHD Syndrome reported in Poland

Radzikowska et al. (2016) report the case of a 54-year-old woman presenting with recurrent pneumothoraces and with recurrent pneumothoraces in her family history. A CT scan showed multiple cysts in the lower parts of both lungs. In addition,  liver and renal cysts were revealed in the abdomen. Genetic analysis revealed a mutation in the FLCN gene (c.469_471delTTC(p.Phe157del)) confirming the diagnosis of BHD.

According to the authors, this is the first case of BHD reported in Poland.

This case study is freely available to download in the BHD Article Library: Clinical Research

New website coming + closing “Living with BHDS” Forum

Hi everyone! We are close to launching our new BHDsyndrome website, we are very excited about it! We will close the Forum “Living with BHD Syndrome” and we suggest that people join the Birt Hogg Dube Syndrome group on Facebook that serves the same purpose: asking questions and sharing experiences. We will keep the Forum info archived and available on the new website. As always suggestions and feedback are very welcome

New study: FLCN mutations in Danish BHD patients

In their new study, Rossing et al. (2016) have identified 13 different variants and 3 common polymorphism in the FLCN gene in 143 Danish patients with suspected BHD syndrome. 6 of these variants are novel, 9 are classified as pathogenic and 1 as likely pathogenic. Single nucleotide polymorphism (SNP) analysis revealed that a specific variant (c.1062+2T>G) is a founder mutation shared among all the Danish carriers. These findings contribute to extend our knowledge of the FLCN mutation spectrum.

Co-existence of BHD and other inherited conditions: new case report

Whitworth et al. (2016) present the case of a 58-year-old woman with a variety of disease manifestations including an oncocytoma in the submandibular gland, presence of multiple hemangiomas/cavernous malformations in the cerebrum and cerebellum, pulmonary bullae, a spontaneous pneumothorax episode, a goitre and facial rash.

From the medical history and clinical manifestations, two rare diseases were considered: BHD and hereditary cavernous cerebral malformations (CCM). Genetic testing of the relevant genes revealed mutations in the FLCN and CCM2 genes. Follow-up scan of the kidneys showed multiple small cysts and pulmonary bullae.

The authors suggest that when potentially novel clinical features are manifested, co-existing conditions should be considered and extensive genetic testing should be performed. The increased use of next generation sequencing in diagnosis is likely to reveal more cases such as this.

This case study is freely available to download in the BHD Article Library: Clinical Research.