The Genetics of Pneumothorax

Abstract

A genetic influence on spontaneous pneumothoraces-those occurring without a traumatic or iatrogenic cause-is supported by several lines of evidence: 1) pneumothorax can cluster in families (i.e., familial spontaneous pneumothorax), 2) mutations in the FLCN gene have been found in both familial and sporadic cases, and 3) pneumothorax is a known complication of several genetic syndromes. Herein, we review known genetic contributions to both sporadic and familial pneumothorax. We summarize the pneumothorax-associated genetic syndromes, including Birt-Hogg-Dubé syndrome, Marfan syndrome, vascular (type IV) Ehlers-Danlos syndrome, alpha-1 antitrypsin deficiency, tuberous sclerosis complex/lymphangioleiomyomatosis, Loeys-Dietz syndrome, cystic fibrosis, homocystinuria, and cutis laxa, among others. At times, pneumothorax is their herald manifestation. These syndromes have serious potential extrapulmonary complications (e.g., malignant renal tumors in Birt-Hogg-Dubé syndrome), and surveillance and/or treatment is available for most disorders; thus, establishing a diagnosis is critical. To facilitate this, we provide an algorithm to guide the clinician in discerning which cases of spontaneous pneumothorax may have a genetic or familial contribution, which cases warrant genetic testing, and which cases should prompt an evaluation by a geneticist.

Prevalence of Birt-Hogg-Dubé Syndrome Determined Through Epidemiological Data on Spontaneous Pneumothorax and Bayes Theorem

“…Indeed, 2 studies showed a prevalence of BHD of 64–86% in patients presenting with apparent PSP and a positive family history of pneumothorax ( 5 , 6 ). It is therefore recommended to systematically look for lung abnormalities and a genetic cause, especially BHD, in any individual presenting with apparent PSP, and even more in case of a positive family history of pneumothorax ( 47 , 48 ).…”

Metachronous recurrent pediatric primary spontaneous pneumothorax: A case presentation and literature review

“…Our patient underwent conservative therapy in the first attack for seven days per pediatric guidelines, even so, this is still debatable and surgeons still in a split decision [ [6] , [7] , [8] , 10 , 11 ].…”

“…The decision for open thoracotomy or VATS is still controversial. The ACCP guidelines recommend a thoracoscopic approach both for PSP and SSP [ 6 ], but a study by Barker et al in 2003 showed fewer recurrence in open (1%) in comparison to VATS [ 14 ]. In 2018 total of 1040 patients underwent a study for the decision of early VATS rather than chest tube management, early VATS is associated with a decreased hospital stay, charges, and readmissions.…”

“…Lopez et al identified blebs/bullae intra-operatively in 98% of the cases [ 3 ], mainly in apices of upper lobes. No exact genetic abnormality identified in PSP cases but some genetic studies of sporadic pneumothorax cohorts have focused on mutation in the folliculin (FLCN) gene that has been mapped to the short arm of chromosome 17 which is the same gene for Birt-Hogg-Dubé syndrome [ 5 , 6 ].…”

“…Management options for PSP in children are extrapolated from adult guidelines, but conservative and needle aspiration are not well supported by many authors. As in adults surgery is indicated in cases with prolonged air leak [ [2] , [3] , [4] , [5] , [6] , [7] ] days after intercostal drainage. Such surgery has progressed from the era of posterolateral thoracotomy to trans-axillary mini-thoracotomy and finally, Video-assisted thoracoscopic surgery (VATS) is increasingly performed in children and has been reported to be both safe and effective by many authors [ [3] , [4] , [5] , 7 , 8 ].…”