Inherited Pulmonary Disorders

Abstract

Hereditary lung diseases can affect the airways (asthma, COPD, cystic fibrosis and primary ciliary dyskinesia), parenchyma (pulmonary fibrosis, Birt–Hogg–Dubé syndrome and, tuberous sclerosis) and vasculature (hereditary haemorrhagic telangiectasia) of the lung. Such conditions include simple monogenic disorders such as Kartagener syndrome and α1‐antitrypsin, wherein mutations of critical genes are sufficient to induce well‐defined disease phenotypes. However, many are complex genetic traits in which inheritance subtly affects pathogenesis, for example asthma and idiopathic pulmonary fibrosis. A greater understanding of the genetic basis of pulmonary conditions has provided new insights into their underlying pathophysiology and helped in some cases to shed light on more common sporadic forms. Importantly, the identification of causative genes has also enabled prenatal diagnosis and genetic counselling to be introduced for many diseases. Key Concepts Common diseases frequently have a genetic component which with the advent of genome‐wide association studies can now be elucidated. The study of rare monogenic disorders can provide important mechanistic clues to the pathogenesis of more common sporadic disease. Pulmonary manifestations can be the presenting feature of several important inherited diseases. Making a definitive genetic diagnosis permits the practicing of personised medicine. Molecular testing using gene panels and whole genome sequencing is revolutionising respiratory medicine.