Secondary spontaneous pneumothorax as the presenting manifestation of Filamin A-associated lung disease

Spontaneous pneumothorax occurs in 14.1 individuals per 100 000 [1]. Patients with pneumothoraces secondary to chronic lung disease tend to be over 50, with males more commonly affected (12.0 versus 4.5 per 100 000 population)[1]. Primary spontaneous pneumothorax has a significant genetic predisposition with approximately 10% of patients having an affected relative. We previously showed that in 26% of such families, a molecular diagnosis can be made by sequencing directed by clinical and radiological assessment [2]. The most common monogenic cause that accounts for half of all familial pneumothoraces is Birt-Hogg-Dubé syndrome, with tuberous sclerosis, Marfan syndrome, vascular Ehlers-Danlos syndrome and Loeys-Dietz syndrome accounting for a majority of the remaining cases [2–4]. However, in 74% of people with familial pneumothorax the cause remains unknown suggesting the existence of unidentified risk genes [2]. Footnotes This manuscript has recently been accepted for publication in the ERJ Open Research . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article. Conflict of Interest: Rudy Sinharay declared grant funding to their institution from the Medical Research Council (experimental medicine grant); honoraria for lectures from Chiesi; and support and travel funding from Chiesi for attending the European Respiratory Society (2019) and British Thoracic Society (2022) conferences. Conflict of Interest: Stefan J. Marciniak is a co-investigator on a grant from the Engineering and Physical Sciences Research Council (EPSRC Ref EP/R03558X/1: "EPSRC IRC in Targeted Delivery for Hard-to-Treat Cancers"); a principal supervisor of PhD studentships sponsored by the Victor Dahdaleh Foundation and the University of Cambridge; sponsor of a Medical Research Council Transition Support Award; and has received research grants from the Medical Research Council (MCMB MR/V028669/1, MCMB MR/Y011813/1); Akero Therapeutics (G115394) and the Myrovlitis Trust (MT22_15). He receives fees from DefiniGEN for participation on a scientific advisory board relating to to modelling alpha1 antitrypsin deficiency using iPSC-derived hepatocytes; and has received travel cost support from the Alpha-1 Foundation, FASEB, Mesothelioma UK and the Telethon Institute of Genetics and Medicine to attend those organisations' conferences. Conflict of Interest: All other authors have nothing to declare.