The study revealed that between one in 2,710 and one in 4,190 people in the general population carry the FLCN gene variant, translating to about one in every 3,000 individuals being potentially at risk
A large-scale genetic study by researchers from the University of Cambridge has found that approximately one in 3,000 people may carry a defective gene variant that significantly increases their risk of developing a punctured lung — a condition medically known as pneumothorax.
Pneumothorax occurs when air leaks into the space between the lung and chest wall, causing the lung to collapse partially or completely. It can lead to sudden and severe chest pain and shortness of breath. While it can often resolve on its own or with basic medical intervention, repeated episodes or underlying genetic causes raise serious health concerns.
The gene in question, FLCN, is linked to a rare inherited disorder called Birt-Hogg-Dubé syndrome (BHD), which is characterised by benign skin tumours, lung cysts, and a heightened risk of kidney cancer. The findings, published in the journal Thorax, stem from a comprehensive analysis involving more than 550,000 individuals.
The study revealed that between one in 2,710 and one in 4,190 people in the general population carry the FLCN gene variant, translating to about one in every 3,000 individuals being potentially at risk. In diagnosed cases of Birt-Hogg-Dubé syndrome, the lifetime risk of experiencing a punctured lung was estimated at 37 per cent. However, among those who carried the FLCN mutation without a BHD diagnosis, the lifetime risk was still considerable at 28 per cent.
More surprisingly, while BHD patients have a 32 per cent risk of developing kidney cancer, this risk dropped drastically to just 1 per cent among carriers of the FLCN mutation who did not present other symptoms of the syndrome.
Professor Stefan Marciniak, lead author of the study, expressed his surprise at this finding. “It was unexpected to see such a stark difference in kidney cancer risk. This suggests that the faulty FLCN gene alone may not be sufficient to cause Birt-Hogg-Dubé syndrome,” he said. “There’s clearly something else going on — perhaps additional genetic, environmental, or epigenetic factors play a role.”
The researchers also noted that about one in 200 tall, thin, young men — typically teenagers or those in their early twenties — will experience a punctured lung. In many cases, this is a one-off event and is treated on an outpatient basis by draining air or fluid from the lungs.
However, when individuals who don’t fit the typical profile — for instance, those in their forties — suffer a punctured lung, further investigation may be warranted. Professor Marciniak and his team explained that such patients should undergo MRI scans to check for characteristic lung cysts located in the lower regions of the lungs, which are a hallmark of Birt-Hogg-Dubé syndrome.
“If these cysts are present, it’s highly likely the person has the syndrome. That diagnosis is crucial because it has implications for the health of the patient and their family members,” said Marciniak.
He stressed the importance of early diagnosis. “The good news is that in most cases, the punctured lung occurs a decade or two before any signs of kidney cancer. That gives us a window of opportunity. We can screen these individuals regularly, and if we detect a tumour, it’s usually early enough to treat and cure.”
The findings underscore the need for increased awareness among healthcare providers regarding the link between spontaneous pneumothorax and potential underlying genetic conditions. Doctors are advised to be alert for atypical cases and refer patients for genetic screening where appropriate.
The study offers hope that individuals at risk of serious complications can be identified early and monitored effectively — potentially saving lives through timely intervention and cancer screening.
