When two or more members within the same family have Idiopathic Pulmonary Fibrosis (IPF) or any other form of Idiopathic Interstitial Pneumonia (IIP), it is called Familial Pulmonary Fibrosis (FPF).  The most common definition of FPF is two or more primary biological family members (parent, child, or sibling) with the diagnosis of IPF or IIP.  However, family members can be second degree as well, for example they can be an aunt or uncle, cousins, etc.

Moreover, FPF can occur with other types of IIP, such as non-specific interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP), respiratory bronchiolitis associated interstitial lung disease (RB-ILD), and cryptogenic organizing pneumonia (COP). 

 

FPF Versus IPF or IIP

Other than appearing to have a hereditary basis, patients with FPF and sporadic IPF or other sporadic forms of IIP have the same symptoms, chest x-ray and CT scan patterns, biopsy findings, treatment options, and prognosis.  FPF and sporadic IIP are considered the same disease, with only the term "familial" designating that there is a family history of IIP.

 

FPF is a "Complex disease"

Complex diseases are likely a combination of a genetic predisposition and an environmental trigger.  Many diseases such as heart disease or cancer that tend to run in families follow this model.  A genetic predisposition may make a person vulnerable to developing a disease, but it may take an environmental exposure to actually cause the disease to appear.  This could be due to known or unknown environmental triggers or lifestyle choices.  There could be other genes that have a protective or negative effect on the lungs that can be disturbed by environmental triggers. More research is needed on complex diseases, especially with apparent hereditary factors.  For example, there are several genes that have sequence changes (mutations) associated with FPF and cigarette smoking within families with pulmonary fibrosis is a major risk factor for developing disease.

 

Inheritance Patterns of FPF

FPF appears to transmit through families in an autosomal dominant fashion with reduced penetrance.  "Autosomal" means that males and females can be affected equally, and both have a 50% chance of passing the genetic factor to each of their offspring.  The 50% chance of passing on the genetic factor is considered "dominant".

"Penetrance" refers to whether an individual who carries a mutation for a genetic disorder will develop disease or not.  In reduced (or incomplete) penetrance, an individual may or may not show disease, even though they carry a genetic mutation for the disorder.  It may take an environmental trigger (such as cigarette smoking) to cause the disease to show up. 

Reduced penetrance makes it difficult to determine risks for the development of disease in individuals who carry the mutations for a genetic disorder.  In other words, if an individual is a carrier for a genetic mutation (for example FPF), reduced penetrance means that person is not 100% guaranteed to develop FPF.

 In some families, reduced penetrance can make the genetic disorder appear to "skip" generations.  Future studies on the genes thus far associated with FPF and the discovery of new genes may clarify penetrance.

 

Genetic Factors Discovered So Far

Genetic factors are suspected to play a role in FPF, and a few genes have been identified.  The genes that have been indentified thus far are known as surfactant protein c (SP-C) and the telomerase genes (TERT and TERC).  However, SP-C and the telomerase genes only account for approximately 10% of families with FPF and <1% of sporadic IPF cases.  It is believed that there are more genes that will be discovered in the future.  Research studies are currently underway investigating additional genetic factors that may cause FPF. 

 

Learn more about FPF on the GeneReviews Web site.

 

This information has been approved by David Schwartz, MD (July 2008).