Familial Interstitial Pneumonia

Abstract

On the basis of the vast amount of evidence presented, there leaves little doubt that familial interstitial pneumonia (FIP) is a recognized entity. FIP may present clinically similar to sporadic cases of idiopathic interstitial pneumonia (IIP) with the family history being the only distinguishing feature, or can present with younger age of onset. The younger age of onset may be a misrepresentation due to heightened awareness of the disease among family members who may seek early screening and are diagnosed early. The genetics of the 2 appear to be telling us something different, as the majority of genes discovered have some overlap between FIP and the sporadic forms of IIP. It is possible that patients with FIP are more heavily weighted with genetic risk factors than their sporadic counterparts. For example, rare variants in TERT or TERC that have large deleterious effects are more penetrant, and have a higher representation in FIP than in sporadic idiopathic pulmonary fibrosis (8% to 18% vs. 1% to 3% respectively), whereas common variants with lower penetrance and small effect may be more prevalent in sporadic idiopathic pulmonary fibrosis. Overall, the genes discovered through familial studies and large genome-wide association studies have confirmed at least 3 genes, TERT, TERC and MUC5B as key genes, as well as several other loci in the development of pulmonary fibrosis. This alone shows that FIP and IIPs in general are multigenic and cannot be labeled as a single-gene disorder. These, along with evidence of environmental components support a multifactorial cause for lung fibrosis within FIP as well as the sporadic forms of IIP.