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Review
. 2019 Jun;31(3):330-339.
doi: 10.1097/MOP.0000000000000751.

Genetic causes of surfactant protein abnormalities

Lawrence M Nogee  1
Affiliations
Review

Genetic causes of surfactant protein abnormalities

Lawrence M Nogee. Curr Opin Pediatr. 2019 Jun.

Abstract

Purpose of review: Mutations 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.

Recent findings: Involved 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.

Summary: Genetic 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.

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Figures

None
Representative histology of surfactant dysfunction in a patient with a mutation located in the SFTPC BRICHOS domain. Wide arrows point to hyperplastic AEC2s, dark arrows indicated proteinaceous material and macrophages in distal airspaces, and white arrows indicate the thickened insterstitium. Photomicrograph courtesy of Susan Wert, Ph.D., Cincinnati Children’s Hospital Medical Center.
See this image and copyright information in PMC

References

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      All children in this study of a large (N = 185) number of ABCA3 deficient patients who had mutations on both ABCA3 alleles predicted to preclude ABCA3 expression (“null alleles”) had severe neonatal RDS and died in the first year of life. These data are important for counseling families and in making a decision whether to pursue lung transplantation.

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