Genetic disorders of surfactant protein dysfunction: when to consider and how to investigate

Genetic mutations affecting proteins required for normal surfactant protein function are a rare cause of respiratory disease. The genes identified that cause respiratory disease are surfactant protein B, surfactant protein C, ATP binding cassette number A3 and thyroid transcription factor-1. Surfactant protein dysfunction syndromes are highly variable in their onset and presentation, and are dependent on the genes involved and environmental factors. This heterogeneous group of conditions can be associated with significant morbidity and mortality. Presentation may be in a full-term neonate with acute and progressive respiratory distress with a high mortality or later in childhood or adulthood with signs and symptoms of interstitial lung disease. Genetic testing for these disorders is now available, providing a non-invasive diagnostic test. Other useful investigations include radiological imaging and lung biopsy. This review will provide an overview of the genetic and clinical features of surfactant protein dysfunction syndromes, and discuss when to suspect this diagnosis, how to investigate it and current treatment options.