Alveolar capillary dysplasia

About: Alveolar capillary dysplasia is a research topic. Over the lifetime, 219 publications have been published within this topic receiving 5569 citations. The topic is also known as: Alveolar capillary dysplasia with misalignment of pulmonary veins.

FOX gene cluster defects in alveolar capillary dysplasia associated with congenital heart disease

Abstract: Objective The objective was to report two new patients with the diagnosis of alveolar capillary dysplasia and congenital heart disease, to describe the associated cardiac defects seen in these cases and in the literature, and to consider recent genetic advances concerning the FOX transcription factor gene cluster in chromosome 16q241q242 Methods We retrospectively analysed the records of all patients with congenital heart disease and alveolar capillary dysplasia seen in the Pediatric Cardiology Department between 2005 and 2010 We reviewed all literature published in the English language relating to cases of alveolar capillary dysplasia and congenital heart disease Results Two infants with alveolar capillary dysplasia and cardiac malformation were identified: one had an atrioventricular septal defect and a de novo balanced reciprocal translocation t(1;16)(q32;q24), the second infant had a ventricular septal defect Analysis of 31 cases of the literature including these new cases showed a predominant association of alveolar capillary dysplasia with obstructive left heart disease (35%), as well as an atrioventricular septal defect (29%) FOX gene cluster defects were identified in eight of these patients Discussion Genetic background of alveolar capillary dysplasia is discussed in the light of the balanced reciprocal translocation t(1;16)(q32;q24) identified in the first child of this report Alveolar capillary dysplasia should be suspected in neonates with congenital heart disease and unexpectedly elevated pulmonary vascular resistances, especially in cases of obstructive left heart disease or atrioventricular septal defect Detecting FOX gene cluster defects should be considered in infants with alveolar capillary dysplasia with or without congenital heart disease

Alveolar Capillary Dysplasia in a Patient with Down's Syndrome.

Abstract: To the Editor, I read the case report on a trisomy 21 patient with associated alveolar capillary dysplasia (ACD) by Shehata and Abramowsky [1] with great interest. This association is unique because it has not been described in the English literature before. Based on the presented clinical and pathologic data, in my opinion, the diagnosis of alveolar capillary dysplasia deserves careful reexamination. The clinical presentation, according to the provided very brief clinical history, is atypical for ACD. The vast majority of patients with ACD present with severe persistent pulmonary hypertension of newborn with rapid progression to respiratory distress requiring medical intervention [2]. ACD is regarded as a fatal disease; death occurs usually within 1 month after birth [2]. In contrast, the patient lacked the characteristic pulmonary history, and there was no mention of the usual pulmonary support that ACD patients require (i.e., extracorporeal membrane oxygenation, nitric oxide treatment). The length of survival of this patient is unusually long (3 months) especially without the above-mentioned treatment modalities. Peculiarly, the cause of death was not pulmonary, but rather septicemia-induced multiorgan failure. Although 2 rare reports documented a prolonged survival in ACD patient (22 days and 101 days), these patients had extensive medical support. Most importantly, the pathologic features, as presented, do not convincingly prove that there was pulmonary involvement by ACD. Figure 2 was intended to illustrate the microscopic diagnostic features of ACD. Personally, I found Figure 2 inadequate to assess the number and location of capillaries in the alveolar septae. In this picture, the authors pointed out ‘‘an occasional capillary,’’ but they did not give a detailed description in the corresponding figure legend. After careful examination I was able to spot a number of areas with similar size and same features. In the discussion, the authors briefly mentioned that the prolonged survival of the patient might be due to patchy involvement of the lung by ACD. Since there was no assessment of how patchy the ACD was in the pathology findings, this statement is not substantiated. Despite its obvious significance, it remains unclear if ACD involved the entire lung or one lobe or was indeed patchy. Moreover, there was no discussion and/or description of typical pulmonary findings in Down’s syndrome (pulmonary hypoplasia with decreased alveolar complexity) [3]. Misalignment of veins alone is not diagnostic for ACD, as it can be part of other lung diseases [4,5]. Lastly, given the patient’s history of mechanical ventilation, one could speculate that the presence of large, thin-walled channels within the pulmonary bronchoarterial units presented on Figure 1 may not be veins, but dilated blood-filled lymphatics. Given the uniqueness of this case, I believe that a more complete description (both clinical and histologic) is warranted. I would like to see the histopathologic evaluation of ACD and its distribution throughout the entire lung, possibly using CD31 immunostaining to better assess the location and number of capillaries with comparison to an agematched control, as well as an immunostain with D2– 40 antibody to differentiate between lymphatics and veins.

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.

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

Abstract: 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.

Maternal somatic mosaicism of FOXF1 mutation causes recurrent alveolar capillary dysplasia with misalignment of pulmonary veins in siblings.

Abstract: Maternal Somatic Mosaicism of FOXF1 Mutation Causes Recurrent Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins in Siblings Ho Ming Luk, Tao Tang, Kwong Wai Richard Choy, Ming For Tony Tong, On Kit Wong, and Fai Man Ivan Lo* Department of Health, Clinical Genetic Service, Hong Kong, China Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, China Department of Pathology, Queen Elizabeth Hospital, Hong Kong, China