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Genetic disorders of surfactant dysfunction

Authors
Lawrence M Nogee, MD
William A Gower, MD
Section Editor
George B Mallory, MD
Deputy Editor
Alison G Hoppin, MD

INTRODUCTION

Genetic surfactant dysfunction disorders are caused by mutations in genes encoding proteins critical for the production and function of pulmonary surfactant. These rare disorders may produce familial or sporadic lung disease, with clinical presentations ranging from neonatal respiratory failure to childhood- or adult-onset interstitial lung disease. An overview of these disorders is presented in the table (table 1).

Interstitial lung diseases in children until recently were categorized by their histologic appearance in a manner similar to that used for adult forms of interstitial lung disease (ILD). In children, the lung histopathology findings associated with desquamative interstitial pneumonitis (DIP) are now known to often result from genetic mechanisms that disrupt normal surfactant production and metabolism. By contrast, DIP in adults is considered to represent a distinct type of ILD, which is strongly associated with cigarette smoking and carries a relatively favorable prognosis [1]. These genetic disorders also result in histopathologic patterns other than DIP, including findings of pulmonary alveolar proteinosis and chronic pneumonitis of infancy. An understanding of the pathogenesis of these disorders permits a mechanistic classification as genetic surfactant dysfunction disorders instead of their previous classification based upon histologic appearance.

Issues related to genetic disorders of surfactant dysfunction will be reviewed here. The classification and description of other interstitial lung diseases in children are discussed separately. (See "Classification of diffuse lung disease (interstitial lung disease) in infants and children".)

PATHOPHYSIOLOGY AND GENETICS

Pulmonary surfactant is a mixture of lipids and proteins that is produced by alveolar type II epithelial cells (AEC2) and secreted into the airspaces. Phospholipids are the major component of surfactant by weight, and are essential for lowering surface tension at the air-liquid interface, which prevents alveolar collapse at end-expiration.

Four proteins highly expressed in the lung and found in surfactant are designated surfactant proteins (SP) A, B, C, and D. Additional proteins including ABCA3 and NKX2.1 are also important for the production of functional surfactant. The surfactant proteins are developmentally regulated, such that their expression increases in later gestation [1-4].

                     

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Literature review current through: Nov 2016. | This topic last updated: Fri May 13 00:00:00 GMT 2016.
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