A Novel De Novo Pathogenic Variant in FOXF1 in a Newborn with Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is an autosomal dominant, fatal developmental disorder of the lungs, with a mortality rate of about 100%. ACD/MPV is caused by mutations in FOXF1. Herein, we describe a newborn boy with ACD/MPV carrying a novel pathogenic variant of FOXF1. The patient developed respiratory distress and severe pulmonary hypertension on the first day of life. Despite aggressive cardiorespiratory management, including veno-venous extracorporeal membrane oxygenation, his condition deteriorated rapidly, and he died within the first month of his life. Lung histology showed the characteristic features of ACD/MPV at autopsy. Sequence analysis of FOXF1 from genomic DNA obtained from autopsied lung tissue revealed that the patient was heterozygous for a novel missense variant (c.305T>C; p.Leu102Pro). Further analysis of both parents confirmed the de novo occurrence of the variant. To the best of our knowledge, this is the first report of genetically confirmed ACD/MPV in Korea.

Enfermedad pulmonar difusa: causa de hipertensión pulmonar persistente antes del año de vida / Diffuse lung disease: cause of persistent pulmonary hypertension before one year of age

En pediatría, la enfermedad vascular pulmonar es multifactorial y heterogénea. Si bien comparte algunas características con la hipertensión pulmonar en los adultos, hay diferencias en las comorbilidades y condiciones asociadas, la coexistencia de enfermedades genéticas o del desarrollo. Las enfermedades pulmonares intersticiales pueden ser causantes de esta entidad. Una de ellas es la displasia alvéolo-capilar con mal alineamiento de las venas pulmonares, una patología infrecuente pero con 100% de mortalidad, caracterizada por la falla en la formación del tejido pulmonar que da por resultado final la alteración en la difusión de gases. Se describe un caso clínico de una paciente de 5 meses de edad estudiada a partir de sospechar una cardiopatía congénita con hipoxemia persistente, a cuyo diagnóstico se llega por la biopsia pulmonar.

Pulmonary vascular disease in children is multifactorial and heterogeneous. While it shares some features with pulmonary hypertension in adults, there are differences in the associated comorbidities and conditions, the coexistence of genetic or developmental diseases. Interstitial lung diseases may be responsible for this entity. One is alveolar capillary dysplasia with misalignment of pulmonary veins, a rare pathology but with a mortality rate of 100%, characterized by a failure in the formation of lung tissue that eventually results in impaired gas diffusion. We present a 5-month-old patient studied due to suspected congenital heart disease with persistent hypoxemia; diagnosis was made through lung biopsy.