Interstitial lung disease (ILD) refers to a broad collection of lung conditions affecting the tissue surrounding the tiny air sacs (alveoli). These disorders cause inflammation and, over time, lead to scarring (fibrosis) of the lung tissue. Scarred tissue thickens and stiffens, making it difficult for oxygen to pass into the bloodstream. Individuals often experience symptoms such as shortness of breath, particularly with activity, and a persistent dry cough.
Understanding Interstitial Lung Disease
ILD is not a single condition but an umbrella term encompassing over 200 distinct disorders. A common characteristic is inflammation and scarring that impacts the interstitium, the delicate tissue supporting the lung’s air sacs. This damage impedes the lungs’ ability to effectively exchange oxygen and carbon dioxide.
The causes of ILD can be broadly categorized. Some forms have known origins, such as exposure to environmental substances like asbestos or silica, certain medications, or as complications of autoimmune diseases like rheumatoid arthritis. However, many types of ILD are classified as idiopathic, meaning their cause remains unknown. Idiopathic pulmonary fibrosis (IPF) is the most common form within this idiopathic category.
When Interstitial Lung Disease is Hereditary
While most ILD cases occur sporadically, a notable subset can be hereditary. When two or more members of the same family are diagnosed with ILD, it is often referred to as familial pulmonary fibrosis (FPF). This familial form accounts for approximately 20% of pulmonary fibrosis cases, with up to 30% of idiopathic pulmonary fibrosis (IPF) patients reporting a family history.
Familial pulmonary fibrosis is the most commonly recognized hereditary form of ILD, often involving immediate family members such as parents, children, or siblings. However, some rarer genetic syndromes can also include ILD as a feature. Examples include Hermansky-Pudlak syndrome (HPS), characterized by oculocutaneous albinism, bleeding issues, and in some types, pulmonary fibrosis. Another is dyskeratosis congenita, a condition associated with premature aging and an increased risk of pulmonary fibrosis.
The Genetic Basis of Hereditary ILD
Hereditary forms of ILD arise from specific genetic mutations passed down through families. For familial pulmonary fibrosis, the inheritance pattern is frequently autosomal dominant. This means that inheriting just one altered copy of a specific gene from an affected parent is sufficient to increase the risk of developing the disorder. While inheriting the gene increases risk, not everyone with the mutation will develop the disease, a concept known as reduced penetrance.
Genetic changes implicated in hereditary ILD often affect genes involved in two primary biological pathways: telomere maintenance and surfactant production. Telomeres are protective caps at the ends of chromosomes, and mutations in genes like TERT, TERC, RTEL1, and PARN can lead to abnormally short telomeres. This cellular dysfunction can contribute to lung scarring. Similarly, mutations in genes such as SFTPB, SFTPC, and ABCA3, which are crucial for producing surfactant (a substance that helps the lung’s air sacs remain open), can disrupt normal lung function and lead to fibrosis. These genetic alterations can initiate an abnormal healing response in the lungs, leading to the progressive accumulation of scar tissue.
Family Implications and Genetic Counseling
A detailed family medical history is an important first step in identifying whether ILD might have a genetic component within a family. This history can reveal patterns of lung disease across generations or among multiple relatives. Recognizing such patterns can guide further investigation and management.
Genetic counseling is important for families with a history of ILD. A genetic counselor can assess the likelihood of a hereditary form, explain inheritance patterns, and discuss the potential for genetic testing. Genetic testing can help clarify a diagnosis, inform family members about their risks, and potentially guide treatment decisions. However, it is important to consider both the benefits of gaining this knowledge and the potential emotional impact and limitations, such as incomplete penetrance.