Chest
Original ResearchGenetic and Developmental DisordersA Mutation in TTF1/NKX2.1 Is Associated With Familial Neuroendocrine Cell Hyperplasia of Infancy
Section snippets
Case History
The proband was born at 39 weeks' gestation with birth weight 3,120 g. There were no neonatal respiratory or other health concerns. Family members noted that she had rapid breathing in the first weeks of life, and she had trouble breastfeeding. Medical evaluations were prompted at 4 months of age due to failure to thrive. At that time, tachypnea and hypoxemia were prominent, and supplemental oxygen was initiated. There were no symptoms of cough, fever, wheezing, or acute infection. Results of
Genetic Investigations
Based on the apparent autosomal-dominant pattern of disease in this family and the known variability of the lung disease associated with SFTPC mutations, this gene was first sequenced in the proband and her mother, with no mutations identified. With the recent recognition of the potential role of NKX2.1 mutations in causing diffuse lung disease in children, we subsequently sequenced NKX2.1 in the proband and found that she is heterozygous for a G to T transversion in codon 191 of NKX2.1 that is
Discussion
NEHI is a distinct entity with well-described clinical, physiologic, radiographic, and histologic features. The incidence and prevalence of NEHI are unknown, although the disorder is felt to be rare. Although mortality due to NEHI has not been reported, it results in significant morbidity in young children.2, 3, 6 Most children require supplemental oxygen for years, and many need additional nutritional support, including via gastrostomy tube in some cases. Hospitalization and overall
Acknowledgments
Author contributions: Dr Nogee had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Dr Young: contributed to study inception and data acquisition and analysis; drafted the manuscript; provided critical input and helped revise the final version of the manuscript; and approved the final version of the manuscript.
Dr Deutsch: contributed to data acquisition and analysis; provided critical input and helped revise
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Funding/Support: This work was supported by grants through the National Institutes of Health [HL54703, Dr Nogee]; American Thoracic Society/chILD Foundation/chILD (Lung) Foundation-UK (Dr Young); and the Eudowood Foundation (Dr Nogee).
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