Genetic basis of familial spontaneous pneumothorax and lung cysts in an Indian family

Abstract

Approximately 10% patients of spontaneous pneumothorax have positive family history. Birt–Hogg–Dube syndrome (BHD) is one of the cause of familial pneumothorax. BHD syndrome is associated with hamartomas of skin,renal cancer and spontaneous pneumothorax. However there have been reports of isolated spontaneous pneumothorax and lung cysts in patients of BHD syndrome in the absence of other manifestations. Mutation in Folliculin gene (FLCN) on chromosome 17 has been reported to cause BHD syndrome. A 32 year old non-smoker female presented with left sided spontaneous pneumothorax. Her sister had previously suffered from recurrent pneumothorax (twice). High Resolution CT (HRCT) scan of chest of both the sisters revealed multiple lung cysts. We decided to evaluate these patients of familial pneumothorax and identify any genetic basis for their disease. Genetic sequencing of the FLCN gene was performed in 8 family members. We subsequently screened the family members by HRCT scan of chest for any lung cysts. Physical examination and abdominal CT scan was done to rule out any skin and renal involvement. Genetic sequencing revealed Cytosine deletion mutation in hypermutable region of exon 11 of FLCN gene in the index case, her 3 siblings, her mother and her son. HRCT scan of the patient9s sibling showed lung cysts whereas her son had normal lungs, despite having the mutation.This cytosine deletion caused a frameshift mutation resulting in a truncated folliculin protein. For cystic lung disease with an undetermined etiology or familial pneumothorax, possibility of BHD syndrome should be considered. Pulmonologists should be aware that BHD syndrome can occur as an isolated phenotype with pulmonary involvement.