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Last updated: 1/14/2025
Years published: 2025
NORD gratefully acknowledges Anna Laemmle, MD Candidate, Tam Nguyen, MD Candidate, University of South Florida Morsani College of Medicine and Katiana Garagozlo, MD, Assistant Professor, University of South Florida Morsani College of Medicine, for the preparation of this report.
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Summary
Surfactant protein C deficiency is a very rare genetic disorder that can cause neonatal respiratory distress syndrome and chronic interstitial lung disease. These issues are primarily characterized by cough, rapid breathing (tachypnea), shortness of breath and low oxygen in the blood (hypoxemia).1 Age of onset is variable, but symptoms may begin between birth and 2 years of age and sometimes further into childhood. Pulmonary surfactant is a material made up of lipids and proteins that coats the microscopic air sacs of the lungs, allowing for lower surface tension which prevents the air sacs from collapsing. Surfactant is a key component to maintain proper function of the lungs.
Deficiency of surfactant protein C is most commonly caused by changes (variants) in the SFTPC gene that result in the surfactant protein C being misfolded and destroyed. The variant can be inherited in an autosomal dominant pattern but can also occur sporadically.2,3
Definitive diagnosis is made with genetic testing or lung biopsy. Physicians may also perform a chest X-ray, computed tomography (CT) of the chest and pulmonary function testing to assess severity. Treatment typically revolves around supportive therapy such as nutritional support and ventilation. Lung transplant may be required in severe cases. Medications such as steroids, hydroxychloroquine and azithromycin may be prescribed depending on severity, as they have been shown to help in some affected people.1, 4
Surfactant protein C deficiency causes interstitial lung disease, which is a broad diagnosis that encompasses diseases with profuse lung scarring. Interstitial lung disease causes symptoms such as cough, rapid breathing (tachypnea) and hypoxemia. Less common symptoms include clubbing of the nails.1 The age at onset is highly variable. While some people have signs during the first few years of life, mildly affected people may develop symptoms in adulthood.
Some people with surfactant C deficiency have symptoms at birth such as neonatal respiratory distress syndrome. In this condition, infants are born with inadequate levels of surfactant and have trouble breathing. They may have tachypnea with shallow breaths, appear to be grunting, flaring their nostrils, have blue-tinged skin and lips and have inward pulling of chest muscles.
Surfactant protein C is caused by a change (variant) in the SFTPC gene. The most common variant causes the surfactant protein C to be misfolded and destroyed so it cannot form functional surfactant. Other variants cause issues with vacuole formation and maturation, which are structures that can clear damaged compounds from the cell. Without these vacuoles, toxic compounds can build up within the cell and cause damage to the lung.5
This condition follows autosomal dominant inheritance but may also occur spontaneously (de novo) in about 55% of cases.
Dominant genetic disorders occur when only a single copy of a disease-causing gene variant is necessary to cause the disease. The gene variant can be inherited from either parent or can be the result of a new (de novo) changed gene in the affected individual that is not inherited. The risk of passing the gene variant from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females.
Surfactant protein C deficiency is very rare and current estimates from the medical literature state an incidence of <1 in 5,000 children.
The diagnosis of surfactant protein C deficiency may be suspected in an infant or young child with symptoms of respiratory distress and/or if there is a family history of the disease. To further assess the disease, images of the lungs through an X-ray and/or CT scan may be done. In children with surfactant protein C deficiency, these images will show diffuse infiltrates throughout both lungs, in the spongy lobes (interstitium) and microscopic air sacs (alveoli).
To confirm the diagnosis, genetic testing is typically performed. This testing involves analyzing a blood sample for variants in the SFTPC gene. If genetic testing and lung imaging are inconclusive, lung biopsy may be performed for diagnosis.6
Pulmonary function tests, a group of tests that measure breathing and how well the lungs are functioning, can also be performed to assess the severity of the disease. These tests determine the capacity of the lungs to inhale, hold and exhale air. Pulmonary function tests in patients with surfactant protein C deficiency range from normal to restrictive (decreased capacity to hold air), suggesting results may be helpful when determining treatment and outcomes.7
Currently there are no specific treatments available for surfactant protein C deficiency. Surfactant replacement therapy may temporarily improve respiratory status, but this is not a long-term treatment plan. In children with milder forms of the disease, there is some data suggesting the efficacy of corticosteroids and hydroxychloroquine to stabilize the disease process until the patient can receive a lung transplant. Lung transplantation may be considered the only potentially curative treatment, but it is associated with chronic medical challenges and long-term health problems, so it is reserved for people with severe and progressive lung disease.8
The multidisciplinary team for people with this diagnosis should include neonatologists, pediatric pulmonologists, geneticists, radiologists and pathologists.
Genetic counseling is recommended for families who have a child with this diagnosis.
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For information about clinical trials sponsored by private sources, contact: www.centerwatch.com
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
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