Genetic causes of surfactant protein abnormalities.

Abstract

PURPOSE OF REVIEW\nMutations in genes encoding proteins critical for the production and function of pulmonary surfactant cause diffuse lung disease. Timely recognition and diagnosis of affected individuals is important for proper counseling concerning prognosis and recurrence risk.\n\n\nRECENT FINDINGS\nInvolved genes include those encoding for surfactant proteins A, B, and C, member A3 of the ATP-binding cassette family, and for thyroid transcription factor 1. Clinical presentations overlap and range from severe and rapidly fatal neonatal lung disease to development of pulmonary fibrosis well into adult life. The inheritance patterns, course, and prognosis differ depending upon the gene involved, and in some cases the specific mutation. Treatment options are currently limited, with lung transplantation an option for patients with end-stage pulmonary fibrosis. Additional genetic disorders with overlapping pulmonary phenotypes are being identified through newer methods, although these disorders often involve other organ systems.\n\n\nSUMMARY\nGenetic disorders of surfactant production are rare but associated with significant morbidity and mortality. Diagnosis can be made invasively through clinically available genetic testing. Improved treatment options are needed and better understanding of the molecular pathophysiology may provide insights into treatments for other lung disorders causing fibrosis.