Showing papers on "Alveolar capillary dysplasia published in 2015"

Diseases of Pulmonary Surfactant Homeostasis

Abstract: Pulmonary surfactant is required for adaptation to air breathing after birth, reducing surface tension at the air-liquid interface in the alveolus to maintain lung volumes during the respiratory cycle. Disorders of pulmonary surfactant homeostasis are associated with acute and chronic respiratory disease in infants and adults. Mutations in the surfactant protein genes encoding SP-B and SP-C cause severe respiratory failure in infancy and chronic interstitial lung disease in older individuals.

Intrapulmonary vascular shunt pathways in alveolar capillary dysplasia with misalignment of pulmonary veins

Abstract: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a lethal neonatal lung disease characterised by severe pulmonary hypertension, abnormal vasculature and intractable hypoxaemia. Mechanisms linking abnormal lung vasculature with severe hypoxaemia in ACD/MPV are unknown. We investigated whether bronchopulmonary anastomoses form right-to-left shunt pathways in ACD/MVP. We studied 2 infants who died of ACD/MPV postmortem with direct injections of coloured ink into the pulmonary artery, bronchial artery and pulmonary veins. Extensive histological evaluations included serial sectioning, immunostaining and 3-dimensional reconstruction demonstrated striking intrapulmonary vascular pathways linking the systemic and pulmonary circulations that bypass the alveolar capillary bed. These data support the role of prominent right-to-left intrapulmonary vascular shunt pathways in the pathophysiology of ACD/MPV.

A late presenter and long-term survivor of alveolar capillary dysplasia with misalignment of the pulmonary veins

Abstract: This report demonstrates a late presenter and long-term survivor (38 months old) of alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) and with a heterozygous frameshift mutation in FOXF1. The mild phenotype may be due to his residual normal lung tissue as demonstrated in the chest computed tomography (CT) and histopathological findings.

A 16q deletion involving FOXF1 enhancer is associated to pulmonary capillary hemangiomatosis

Abstract: Pulmonary capillary hemangiomatosis (PCH) is an uncommon pulmonary disorder, with variable clinical features depending on which lung structure is affected, and it is usually linked to pulmonary arterial hypertension. Congenital PCH has been very rarely described and, so far, the only causative gene identified is EIF2AK4, which encodes for a translation initiation factor. However, not all PCH cases might carry a mutation in this gene. We report the clinical and cytogenetic characterization of a patient (male, newborn, first child of healthy non-consanguineous parents) died after three days of life with severe neonatal pulmonary hypertension, due to diffuse capillary hemangiomatosis diagnosed post mortem. Conventional karyotyping, Microarray-Based Comparative Genomic Hydridization (CGHa) and quantitative PCR were performed. CGHa revealed a heterozygous chromosome 16q23.3q24.1 interstitial deletion, spanning about 2.6 Mb and involving a FOXF1 gene enhancer. Quantitative PCR showed that the proband’s deletion was de novo. Microsatellite analysis demonstrate that the deletion occurred in the maternal chromosome 16. FOXF1 loss of function mutation have been so far identified in alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), a lung disease different from PCH. Our data suggest the hypothesis that disruption of the FOXF1 gene enhancer could be a genetic determinant of PCH. Moreover, our findings support the idea that FOXF1 is a paternally imprinted gene.

Irreversible Respiratory Failure in a Full-Term Infant with Features of Pulmonary Interstitial Glycogenosis as Well as Bronchopulmonary Dysplasia.

Abstract: Pulmonary interstitial glycogenosis (PIG) is a rare interstitial lung disease in the newborns. We report on the clinical presentation and pathological findings of a full-term male infant with pulmonary hypertension requiring extracorporeal membrane oxygenation (ECMO). An open lung biopsy demonstrated interstitial changes resembling pulmonary interstitial glycogenosis as well as bronchopulmonary dysplasia (BPD), without convincing evidence of maturational arrest, infection, alveolar proteinosis, or alveolar capillary dysplasia. The boy was treated with glucocorticoids and, after a few days, was weaned from ECMO. A few hours later, the patient died due to acute severe pulmonary hypertension with acute right ventricular failure. The etiology and underlying pathogenic mechanisms of PIG are unknown. The clinical outcomes are quite varied. Deaths have been reported when PIG exists with abnormal lung development and pulmonary vascular growth and congenital heart disease. No mortality has been reported in PIG together with BPD in full-term infants. In this article, we reported on a full-term infant with interstitial changes resembling PIG and BPD who expired despite no convincing evidence of an anatomical maturational arrest or congenital heart disease.

The Respiratory System

Abstract: The respiratory system comprises the lips and palate, larynx, trachea, lungs, and diaphragm, and their development and abnormalities of development are described. Pulmonary cystic disease forms one such group of developmental abnormalities and includes congenital lobar emphysema, congenital pulmonary adenomatoid malformation (CPAM), and pulmonary sequestration. Maturation of the lung can be terminated if delivery occurs early, leading to respiratory distress clinically, which has been ameliorated by antenatal steroids and antioxidants and postdelivery surfactant therapy. The causes and pathology of respiratory distress in the newborn are described; these include hyaline membrane disease and meconium aspiration syndrome, as well as rarer entities such as surfactant protein deficiency and alveolar capillary dysplasia. The clinical and pathology characteristics of chronic lung disease have changed over the last 20 years, and bronchopulmonary dysplasia, “old” and “new,” are described.

Alveolar Capillary Dysplasia as a Cause of Persistent Pulmonary Hypertension.

Abstract: Background Persistent pulmonary hypertension (PPHN) in a term or late preterm has varied etiology.

A novel FOXF1 mutation associated with alveolar capillary dysplasia and coexisting colobomas and hemihyperplasia

Abstract: Alveolar capillary dysplasia (ACD) is a rare and lethal cause of hypoxic respiratory failure in the neonate. Here we describe a term neonate with ACD that was found with a previously unreported p.Arg86Pro mutation in the FOXF1 (Forkhead Box-F1) gene and coexisting congenital anomalies, including colobomas of the iris and hemihyperplasia. This unique clinical presentation may indicate a novel, yet unconfirmed disease association for mutations in the FOXF1 gene. Rapid mutation analysis in FOXF1 may provide noninvasive early confirmation of ACD in neonates with respiratory failure and can aid in clinical decision making.

Dysplasie alvéolo-capillaire avec mésalignement des veines pulmonaires : une cause de cyanose néonatale réfractaire létale

Abstract: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare neonatal pathology that combines refractory hypoxemia with severe pulmonary arterial hypertension, and leads to death every time. Histologic examination of lung tissue confirms the diagnosis and is characterized by a decreased number of pulmonary capillaries, immature lobular development, and abnormal proximity between pulmonary arteries and veins. This abnormal proximity is responsible for an arteriovenous shunt. We report five cases confirmed by postmortem histology, which occurred over 14 years in Lower Normandy (France). The cumulative incidence is therefore of 1.8 for 100,000 births. In these five cases, the first symptoms appeared during the first hour of life and death occurred before 24h in four of five cases. The patient with the longest survival had mild histological lesions and delayed emergence of the first symptoms. Genitourinary and gastrointestinal anomalies were associated with ACD/MPV in two cases, and bilateral pulmonary hypoplasia in three cases. Optimized invasive ventilation, pulmonary vasodilators, vasoactive drugs, and pulmonary surfactant did not improve survival. Extracorporeal membrane oxygenation (ECMO) was not used. We present a review of the literature on ACD/MPV, a clinical and histological entity little known to both clinicians and pathologists, whereas a premortem diagnosis is possible and genetic counseling in affected families can be suggested.

A Novel Mutation in FOXF1 Gene Associated with a Delayed Presentation of Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins

Abstract: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, fatal developmental lung disorder of neonates and infants, associated with severe persistent pulmonary hypertension unresponsive to treatment. We reported the case of a term newborn with delayed presentation of ACD/MPV and a novel mutation of FOXF1 gene that received supportive cardiopulmonary treatments, inhaled nitric oxide, oral sildenafil and nebulized iloprost with no clinical improvement. DNA sequence analysis of FOXF1 gene identified a novel heterozygous variant c.257G > C; p.R86P, in exon 1. At autopsy, lung histology showed the characteristic features of ACD/MPV. FOXF1 has been identified as one of the genes responsible for ACD/MPV associated with multiple congenital malformations. This is a report of a novel heterozygous variant c.257G > C; p.R86P, in the first exon of FOXF1, in a patient with delayed presentation of ACD/MPV.

Diffuse pulmonary development disorders- Molecular definable causes of pulmonary hypertension in the mature newborn

Abstract: Background: Acinar dysplasia and alveolar capillary dysplasia are rare interstitial lung diseases, belonging to the diffuse developmental disorders of the lungs. About 10% of the cases are familiar, 40% carry a FOXF1-mutation. Usually disease starts on the first days of life with severe hypoxia, and is mostly lethal during the newborn period. Aims: Investigate the clinical, histological and genetic spectrum of this orphan disease and differentiate subtypes Methods: All patients categorized as diffuse developmental disorder in the kids lung register were searched. Diagnosis was made by lung biopsy or autopsy. Between October 2004 and October 2014 11 children were observed and analysed retrospectively. Results: All children had a need for oxygen during the neonatal time. 7 children developed severe hypoxemia and pulmonary hypertension at the latest 48 hours after initial good adaptation. An infant with an omphalocele and one preterm-infant needed oxygen immediately after birth. In one infant symptoms started not until day 12 of life, he showed complete remission at the age of 29 days. Outcome was lethal in 8 children at an average age of 44 days. In 4 patients FOXF1 gene was analysed and two heterozygote deletions were detected. Conclusion: Diffuse developmental disorders of the lungs represent a rare but important differential diagnosis in children with hypoxemia and pulmonary hypertension. Fatality was associated with histologic pattern, i.e. presence of misalignment of the pulmonary veins. Screen for disease causing mutations in the FOXF1-gene, particular in infants with associated malformations, may reduce the number of lung biopsies necessary for diagnosis.

Recurrence of alveolar capillary dysplasia with misalignment of pulmonary veins in two consecutive siblings.

Abstract: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, developmental lung disorder, which has been increasingly reported. This entity usually presents as neonatal persistent pulmonary hypertension that is unresponsive to treatment, and is known to be uniformly fatal. Recent discoveries in the genetic field, and intensive treatments, may change the natural course of this disease, permitting easier diagnosis and giving new hope for the dismal prognosis. The authors present two cases of siblings, with two years of difference, from different fathers - one of them was a first-degree and the other a second-degree cousin of the mother. Both patients were full-term babies born apparently without malformations and were sent to the nursery. Both siblings near 35 hours of age presented severe respiratory failure due to pulmonary hypertension. The outcome was fatal in both cases and at autopsy ACD/MPV was diagnosed. The authors call attention to this entity in the differential diagnosis of acute respiratory distress in early life.