Journal Articles

The number of journal papers and other articles in the medical literature published about ACDMPV is growing as awareness of the condition grows within the medical community. Below, in publication date order, is a list of articles we are aware of that have been published on ACDMPV. We attempt to provide the most comprehensive database of information on ACDMPV and appreciate any information concerning additional articles or other literature that becomes available.

2020s
 
 
 
 
 
 
 
2022
2021
2020
 
2010s
2019
2018
2017
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2015
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2013
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2022

2021

    • Genetics and Epigenetics of Alveolar Capillary Dysplasia: From bedside to bench
      E. Heuberger-Slot (Evelien) (2021). Doctoral Thesis,Erasmus University Rotterdam.
      https://repub.eur.nl/pub/137025
    • Detection of low-level parental somatic mosaicism for clinically relevant SNVs and indels identified in a large exome sequencing dataset
      Daniel D Domogala, Tomasz Gambin, Roni Zemet, Chung Wah Wu, Katharina V Schulze, Yaping Yang, Theresa A Wilson, Ido Machol, Pengfei Liu, Paweł Stankiewicz (2021). Hum Genomics. 2021 Dec 20;15(1):72. doi: 10.1186/s40246-021-00369-6.
      https://pubmed.ncbi.nlm.nih.gov/34930489//
    • Fetal lung development via quantitative biomarkers from diffusion MRI and histological validation in rhesus macaques
      Nara S Higano, Xuefeng Cao, Jinbang Guo, Xiaojie Wang, Christopher D Kroenke, Alyssa L Filuta, James P Bridges, Jason C Woods (2021). J Perinatol. 2021 Oct 22. doi: 10.1038/s41372-021-01236-x. Online ahead of print.
      https://pubmed.ncbi.nlm.nih.gov/34686834/
    • A Case of Alveolar Capillary Dysplasia in a Persistently Hypoxic Infant
      B Young, S Kirkby, L Ulrich (2021). Genetic and Developmental Disorders| Volume 160, ISSUE 4, SUPPLEMENT, A1434, October 01, 2021.
      https://doi.org/10.1016/j.chest.2021.07.1313
    • [The role of FOXF1 and Serotonin transporter in alveolar capillary dysplasia with misalignment of pulmonary veins with differential diagnosis] [article written in Chinese]
      Zhonghua Bing Li Xue Za Zhi . 2021 Jul 8;50(7):811-813. doi: 10.3760/cma.j.cn112151-20210329-00241.
      https://pubmed.ncbi.nlm.nih.gov/34405622/
    •  Nanoparticle-Facilitated Gene Delivery in Congenital Pulmonary Vascular Disease: Roadmap for Other Forms of Pulmonary Hypertension.
      Jane A Leopold (2021). Circulation. 2021 Aug 17;144(7):556-558. doi: 10.1161/CIRCULATIONAHA.121.055345. Epub 2021 Aug 16.
      https://pubmed.ncbi.nlm.nih.gov/34398687/
    • Therapeutic Potential of Endothelial Progenitor Cells in Pulmonary Diseases.
      Olena A Kolesnichenko, Jeffrey A Whitsett, Tanya V Kalin, Vladimir V Kalinichenko (2021). Am J Respir Cell Mol Biol. 2021 Jul 22. doi: 10.1165/rcmb.2021-0152TR. Online ahead of print.
      https://pubmed.ncbi.nlm.nih.gov/34293272/
    • Nanoparticle Delivery of STAT3 Alleviates Pulmonary Hypertension in a Mouse Model of Alveolar Capillary Dysplasia.
      Fei Sun, Guolun Wang, Arun Pradhan, Kui Xu, Jose Gomez-Arroyo, Yufang Zhang, Gregory T Kalin, Zicheng Deng, Ronald J Vagnozzi, Hua He, Andrew W Dunn, Yuhua Wang, Allen J York, Rashmi S Hegde , Jason C Woods, Tanya V Kalin, Jeffery D Molkentin, Vladimir V Kalinichenko (2021). 2021 Aug 17;144(7):539-555.
      doi: 10.1161/CIRCULATIONAHA.121.053980. Epub 2021 Jun 11.
      https://pubmed.ncbi.nlm.nih.gov/34111939/
    • Generation of Pulmonary Endothelial Progenitor Cells for Cell-Based Therapy Using Interspecies Mouse-Rat Chimeras.
      Guolun Wang, Bingqiang Wen, Xiaomeng Ren, Enhong Li, Yufang Zhang, Minzhe Guo, Yan Xu, Jeffrey A Whitsett, Tanya V Kalin, Vladimir V Kalinichenko (2021). Am J Respir Crit Care Med. 2021 Mar 11. doi: 10.1164/rccm.202003-0758OC. Online ahead of print.
      https://pubmed.ncbi.nlm.nih.gov/33705684/
    • Lung-specific distant enhancer cis regulates expression of FOXF1 and lncRNA FENDRR.
      Przemyslaw Szafranski, Tomasz Gambin, Justyna A Karolak, Edwina Popek, Paweł Stankiewicz (2021).
      Hum Mutat. 2021 Jun;42(6):694-698. doi: 10.1002/humu.24198. Epub 2021 Apr 6.
      https://pubmed.ncbi.nlm.nih.gov/33739555/
    • Two cases of different genetic variants of alveolar capillary dysplasia associated with left-sided obstructive CHDs.
      Josue Diaz-Frias, Paul R Mark, E Oliver Aregullin (2021). Cardiol Young. 2021 Mar 5;1-3. doi: 10.1017/S1047951121000676. Online ahead of print.
      https://pubmed.ncbi.nlm.nih.gov/33663630/
    • Nanoparticle Delivery Systems with Cell-Specific Targeting for Pulmonary Diseases.
      Zicheng Deng, Gregory T Kalin, Donglu Shi, Vladimir V Kalinichenko (2021). Am J Respir Cell Mol Biol. 2021 Mar;64(3):292-307. doi: 10.1165/rcmb.2020-0306TR.
      https://pubmed.ncbi.nlm.nih.gov/33095997/
    • Early prenatal diagnosis of alveolar capillary dysplasia with misalignment of pulmonary veins due to a 16q24.1 deletion.
      Chloé Puisney-Dakhli, Francesca Gubana, François Petit, Hanane Bouchghoul, Valérie Gautier, Jelena Martinovic, Gérard Tachdjian, Aline Receveur (2021). Cardiol Young. Am J Med Genet A. 2021 May;185(5):1494-1497. doi: 10.1002/ajmg.a.62105. Epub 2021 Jan 31.
      https://pubmed.ncbi.nlm.nih.gov/33522073/

2020

    • Alveolar capillary dysplasia with misalignment of the pulmonary veins: a case report and literature review.
      [Article in Chinese], Y Lin, J B Jiang, B Xia, J Cao, A Z Yu, W M Huang (2020) Zhonghua Er Ke Za Zhi. 2020 Oct 2;58(10):838-842. doi: 10.3760/cma.j.cn112140-20200427-00441.
      https://pubmed.ncbi.nlm.nih.gov/32987465/
    • Histopathologic Features of Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins with Atypical Clinical Presentation.
      Murad Alturkustani, Duo Li, Joshua T Byers, Linda Szymanski, David M Parham, Wei Shi, Larry L Wang. (2020) Cardiovasc Pathol. 2020 Sep 16;107289. doi: 10.1016/j.carpath.2020.107289. Online ahead of print.
      https://pubmed.ncbi.nlm.nih.gov/32949727/
    • In Vivo Generation of Lung and Thyroid Tissues from Embryonic Stem Cells using Blastocyst Complementation.
      Bingqiang Wen, Enhong Li, Vladimir Ustiyan , Guolun Wang , Minzhe Guo , Cheng-Lun Na , Gregory T. Kalin, Veronica Galvan, Yan Xu, Timothy E Weaver, Tanya V. Kalin, Jeffrey A Whitsett, and Vladimir V. Kalinichenko. (2020) Am J Respir Crit Care Med. 2020 Sep 2. doi: 10.1164/rccm.201909-1836OC. Online ahead of print.
      https://pubmed.ncbi.nlm.nih.gov/32877203/

“Abstract: A patient with alveolar capillary dysplasia has survived more than 56 months with medical therapy. Intrauterine exposure to metformin potentially modified the severity of disease. In combination with other agents, endothelin receptor antagonists and amlodipine have been key medications in lowering pulmonary arterial pressure and managing right heart failure.”

Abstract– Purpose of the Review: Significant numbers of patients worldwide are affected by various rare diseases, but the effective treatment options to these individuals are limited. Rare diseases remain underfunded compared with more common diseases, leading to significant delays in research progress and ultimately, to finding an effective cure. Here, we review the use of genome editing tools to understand the pathogenesis of rare diseases and develop additional therapeutic approaches with a high degree of precision.

Recent Findings: Several genome-editing approaches, including CRISPR/Cas9, TALEN, and ZFN, have been used to generate animal models of rare diseases, understand the disease pathogenesis, correct pathogenic mutations in patient-derived somatic cells and iPSCs, and develop new therapies for rare diseases. The CRISPR/Cas9 system stands out as the most extensively used method for genome editing due to its relative simplicity and superior efficiency compared with TALEN and ZFN. CRISPR/Cas9
is emerging as a feasible gene-editing option to treat rare monogenic and other genetically defined human diseases.

Summary:Less than 5% of ~ 7000 known rare diseases have FDA-approved therapies, providing a compelling need for additional research and clinical trials to identify efficient treatment options for patients with rare diseases. Development of efficient genome-editing tools capable to correct or replace dysfunctional genes will lead to novel therapeutic approaches in these diseases.

    • Fast detection of FOXF1 variants in patients with alveolar capillary dysplasia with misalignment of pulmonary veins using targeted sequencing
      Evelien Slot, Jan H von der Thüsen, Arno van Heijst, Ronald van Marion, Frank Magielsen, Hendrikus J Dubbink, Martin Post, Anne Debeer, Dick Tibboel, Robbert J Rottier, Annelies de Klein (2020): Pediatr Res 2020 May 15. doi: 10.1038/s41390-020-0931-5. Online ahead of print.
      https://www.ncbi.nlm.nih.gov/pubmed/32338996

Germany “A newborn infant patient presented with persistent pulmonary hypertension. For right ventricular decompression, the ductus arteriosus was kept open by prostaglandin E1 infusion and was stented at the age of 4 weeks during heart catheterization. The child was weaned from mechanical ventilation, since pulmonary functions were adequate. A small atrial septal defect was identified and closed in cardiac catheterization laboratory to decrease preductal hypoxemia. Diagnostic workup led to the diagnosis of alveolar capillary dysplasia with misalignment of the pulmonary veins. Suprasystemic pulmonary arterial hypertension with persisting nitric oxide dependency remained the leading symptoms. The child underwent bilateral lung transplantation at the age of 28 months. He is well at the age of 44 months.”

    • Nanoparticle Delivery of Angiogenic Gene Therapy: Save the Vessels, Save the Lung!
      Zepp JA, Alvira CM (2020): Am J Respir Crit Care Med. 2020 Apr 27. doi: 10.1164/rccm.202004-0933ED. [Epub ahead of print]
      https://www.ncbi.nlm.nih.gov/pubmed/32338996

Comments on the article linked below, Nanoparticle Delivery of Proangiogenic Transcription Factors into the Neonatal Circulation Inhibits Alveolar Simplification Caused by Hyperoxia.

    • Nanoparticle Delivery of Proangiogenic Transcription Factors into the Neonatal Circulation Inhibits Alveolar Simplification Caused by Hyperoxia.
      Bolte C, Ustiyan V, Ren X, Dunn AW, Pradhan A, Wang G, Kolesnichenko OA, Deng Z, Zhang Y, Shi D, Greenberg JM, Jobe AH, Kalin TV, Kalinichenko VV.(2020): Am J Respir Crit Care Med. 2020 Apr 2. doi: 10.1164/rccm.201906-1232OC. [Epub ahead of print]
      https://www.ncbi.nlm.nih.gov/pubmed/32240596

“Nanoparticle delivery of FOXM1 or FOXF1 stimulates lung angiogenesis and alveolarization during recovery from neonatal hyperoxic injury. Delivery of proangiogenic transcription factors has promise as a therapy for BPD in preterm infants.” “The FOXF1 itself could be potentially used in ACDMPV (avoiding all potential questions about adverse effects of STAT3).”

    • Highly sensitive blocker displacement amplification and droplet digital PCR reveal very low-level parental FOXF1 somatic mosaicism in families with ACDMPV.
      Karolak J, Liu Q, Xie NG, Wu LR, Rocha G, Fernandes S, Ho-Ming L, Lo IF, Mowat D, Fiorino EK, Edelman M, Fox J, Hayes DA, Witte D, Parrott A, Popek E, Szafranski P, Zhang DY, Stankiewicz P. (2020): J Mol Diagn. 2020 Feb 6. pii: S1525-1578(20)30012-X. doi: 10.1016/j.jmoldx.2019.12.007. [Epub ahead of print]
      https://www.ncbi.nlm.nih.gov/pubmed/32036090
    • Generation of three iPSC lines from two patients with heterozygous FOXF1 mutations associated to Alveolar Capillary Dysplasia with Misalignment of the Pulmonary Veins.
      Slot E, de Klein A, Rottier RJ. (2020): Stem Cell Res. 2020 Apr;44:101745. doi: 10.1016/j.scr.2020.101745. Epub 2020 Mar 4.
      https://www.ncbi.nlm.nih.gov/pubmed/32169823
    • A familial case of alveolar capillary dysplasia with misalignment of the pulmonary veins: the clinicopathological features and unusual glomeruloid endothelial proliferation.
      Kitano A, Nakaguro M, Tomotaki S, Hanaoka S, Kawai M, Saito A, Hayakawa M, Takahashi Y, Kawasaki H, Yamada T, Ikeda M, Onda T, Cho K, Haga H, Nakazawa A, Minamiguchi S. (2020): Diagn Pathol. 2020 May 9;15(1):48. doi: 10.1186/s13000-020-00972-6.
      https://www.ncbi.nlm.nih.gov/pubmed/32386508

A familial case study out of Japan.

2019

    • Living-donor single-lobe lung transplantation for pulmonary hypertension due to alveolar capillary dysplasia with misalignment of pulmonary veins.
      Nakajima D, Oda H, Mineura K, Goto T, Kato I, Baba S, Ikeda T, Chen-Yoshikawa TF, Date H. (2019): In: Am J Transplant. 2019 Dec 28. doi: 10.1111/ajt.15762. [Epub ahead of print]
      https://www.ncbi.nlm.nih.gov/pubmed/31883304

Abstract: This is a case report of successful single-lobe lung transplantation for pulmonary hypertension secondary to alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). A 6-year-old boy underwent living-donor single-lobe transplantation with the right lower lobe from his 31-year-old mother. Chest CT showed a mass rapidly growing in the native left upper lobe six months after transplantation, which was diagnosed as post-transplant lymphoproliferative disorder (PTLD) by a CT-guided biopsy. After immunosuppressant reduction and six courses of chemotherapy with rituximab, he underwent native left upper lobectomy for salvage lung resection 13 months after transplantation. Seven months after lobectomy, he has returned to normal school life without any sign of tumor recurrence.

    • Disruption of normal patterns of FOXF1 expression in a lethal disorder of lung development.
      Steiner LA, Getman M, Schiralli Lester GM, Iqbal MA, Katzman P, Szafranski P, Stankiewicz P, Bhattacharya S, Mariani T, Pryhuber G, Lin X, Young JL, Dean DA, Scheible K. (2019): In: J Med Genet. 2019 Oct 29. pii: jmedgenet-2019-106095. doi: 10.1136/jmedgenet-2019-106095. [Epub ahead of print]
      https://www.ncbi.nlm.nih.gov/pubmed/31662342
    • Molecular, cellular, and bioengineering approaches to stimulate lung regeneration after injury.
      Bolte, Craig; Kalin, Tanya; Kalinichenko, Vladimir (2019): In: J Med Genet. 2019 Oct 29. pii: jmedgenet-2019-106095. doi: 10.1136/jmedgenet-2019-106095. [Epub ahead of print]https://www.researchgate.net
    • Phenotypic and genetic spectrum of alveolar capillary dysplasia: a retrospective cohort study.
      Laurélia Jourdan-Voyen, Renaud Touraine, Jean-Pierre Masutti, Tiffany Busa, Catherine Vincent-Delorme, Lelia Dreyfus, Arnaud Molin, Baptiste Savey, Abraham Mounzer, Ziad Assaf, Veronique Atallah11, Vanessa da Cruz, Dominique Gaillard, Elise Leroy-Terquem, Jean-Baptiste Mouton, Jamal Ghoumid, Jean-Charles Picaud, Frederique Dijoud, Sonia Bouquillon, Cédric Baumann, Laetitia Lambert (2019): In: Archives of Disease in Childhood – Fetal and Neonatal Edition Published Online First: 22 October 2019. doi: 10.1136/archdischild-2019-317121 https://fn.bmj.com/content/early/2019/10/22/archdischild-2019-317121

A retrospective observational study in French hospitals (2005-2017).

    • Synchrotron-based phase-contrast micro-CT as a tool for understanding pulmonary vascular pathobiology and the 3-D microanatomy of alveolar capillary dysplasia.
      Norvik C, Westöö CK, Peruzzi N, Lovric G, van der Have O, Mokso R, Jeremiasen I, Brunnström H, Galambos C, Bech M, Tran-Lundmark K. (2019): In: Am J Physiol Lung Cell Mol Physiol. 2020 Jan 1;318(1):L65-L75. doi: 10.1152/ajplung.00103.2019. Epub 2019 Oct 9.https://www.ncbi.nlm.nih.gov/pubmed/31596108
    • Association of rare non-coding SNVs in the lung-specific FOXF1 enhancer with a mitigation of the lethal ACDMPV phenotype.
      Szafranski P, Liu Q, Karolak J, Song X, de Leeuw N, Faas B, Gerychova R, Janku P, Jezova M, Valaskova I, Gibbs KA8, Surrey LF, Poisson V, Bérubé D, Oligny LL, Michaud JL, Popek E, Stankiewicz P.(2019): In: Hum Genet. 2019 Dec;138(11-12):1301-1311. doi: 10.1007/s00439-019-02073-x. Epub 2019 Nov 4.
      https://www.ncbi.nlm.nih.gov/pubmed/31686214

This paper provides more data confirming a well defined core enhancer segment ~ 4 kb in size, which is critical for regulation of FOXF1 expression.

    • Two autopsy cases of siblings with alveolar capillary dysplasia: clinical and post-mortem issues.
      Petetta C, Tattoli L, Botta G, Di Vella G. (2019): In: Journal of Pediatrics. DOI: Forensic Sci Med Pathol. 2019 Sep 11. doi: 10.1007/s12024-019-00153-y. [Epub ahead of print]
      https://www.ncbi.nlm.nih.gov/pubmed/31512071
    • A recurrent 8 bp frameshifting indel in FOXF1 defines a novel mutation hotspot associated with alveolar capillary dysplasia with misalignment of pulmonary veins. Karolak JA, Bacolla A, Liu Q, Lantz PE, Petty J, Trapane P, Panzer K, Totapally BR, Niu Z, Xiao R, Xie NG, Wu LR, Szafranski P, Zhang DY, Stankiewicz P. (2019): In: Am J Med Genet A. 2019 Nov;179(11):2272-2276. doi: 10.1002/ajmg.a.61338. Epub 2019 Aug 22. https://www.ncbi.nlm.nih.gov/pubmed/31436901
    • A Step toward Treating a Lethal Neonatal Lung Disease. STAT3 and Alveolar Capillary Dysplasia. Wambach JA, Nogee LM. (2019): In: Am J Respir Crit Care Med. 2019 Oct 15;200(8):961-962. doi: 10.1164/rccm.201906-1102ED. https://www.ncbi.nlm.nih.gov/pubmed/31343895

Comments on the article linked below, The S52F FOXF1 Mutation Inhibits STAT3 Signaling and Causes Alveolar Capillary Dysplasia.

    • Postnatal Alveologenesis Depends on FOXF1 Signaling in c-KIT+ Endothelial Progenitor Cells.
      Ren X, Ustiyan V, Guo M, Wang G, Bolte C, Zhang Y, Xu Y, Whitsett JA, Kalin TV, Kalinichenko VV. (2019): In: American Journal of Respiratory and Critical Care Medicine, 2019 Jun 24. doi: 10.1164/rccm.201812-2312OC. [Epub ahead of print]
      https://www.ncbi.nlm.nih.gov/pubmed/31233341

Possible therapeutic approach (pending the development of a clinical trial): Cell transplantation of c-KIT-positive endothelial progenitor cells from donor lungs, to increase the development of pulmonary capillaries in ACDMPV babies

    • The S52F FOXF1 Mutation Inhibits STAT3 Signaling and Causes Alveolar Capillary Dysplasia.
      Arun Pradhan, Andrew Dunn, Vladimir Ustiyan, Craig Bolte, Guolun Wang, Jeffrey A Whitsett, Yufang Zhang, Alexey Porollo, Yueh-Chiang Hu, Rui Xiao, Przemyslaw Szafranski, Donglu Shi, Paweł Stankiewicz, Tanya V. Kalin, Vladimir V. Kalinichenko. (2019): In: American Journal of Respiratory and Critical Care Medicine, 2019 Jun 14. doi: 10.1164/rccm.201810-1897OC. [Epub ahead of print]
      https://www.ncbi.nlm.nih.gov/pubmed/31199666

Possible therapeutic approach (pending the development of a clinical trial): Nanoparticle technology delivering a STAT3 protein to the lungs of babies, which could trigger the development of blood vessels in the lungs

Scientists used a gene editing method called CRISPR/Cas9 to generate mice that faithfully mimic a fatal respiratory disorder in newborn infants that turns their lips and skin blue. The new laboratory model allowed researchers to pinpoint the ailment’s cause and develop a potential and desperately needed nanoparticle-based treatment.

Mostly untreatable, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV) usually strikes infants within a month of birth, according researchers at Cincinnati Children’s Hospital Medical Center, who publish findings in the American Journal of Respiratory and Critical Care Medicine. The disease starves the pulmonary system of oxygen after the lung’s blood vessels don’t form properly during organ development. The lack of tiny blood vessels called alveolar capillaries causes hypoxia, inflammation and death.

“There are no effective treatments other than a lung transplant, so the need for new therapeutics is urgent,” said Vlad Kalinichenko, MD, PhD, at the Cincinnati Children’s Perinatal Institute Center for Lung Regenerative Medicine and lead study investigator. “We identified a nanoparticle therapeutic strategy to increase the number of alveolar capillaries and help preserve respiratory function for at least a subset of the babies with this congenital lung disease.”

The disease has long been linked to mutations in the FOXF1 gene, an important regulator of embryonic lung development. The remaining mystery until this study is precise microbiological processes that fuel ACDMPV, according to the researchers.

Uncovering the STAT3 Connection

In collaboration with the team of Pawel Stankiewicz, MD, at the Baylor College of Medicine in Houston, the Kalinichenko lab analyzed genetic information from human ACDMPV cases to generate the first clinically relevant animal model of ACDMPV. They used CRISPR/Cas9 to recreate human FOXF1 mutations in the mouse. CRISPR-Cas9 allows precise gene editing by using an enzyme to cut out specific sections of a DNA sequence and reattaching the loose ends at a desired point to change a cell’s genetic makeup.

Having clinically accurate mouse models of disease ACDMPV allowed the scientists to overcome a longtime hurdle to understanding how the disease develops, authors write.

The work also relied on extensive bioinformatics analyses of clinical and laboratory data from biological tests. This includes a technique called ChIP-Seq (which analyzes protein-DNA interactions), and whole exome sequencing (which reveals the arrangement of all protein-coding regions of genes).

By studying protein-DNA interactions linked to the FOXF1 gene in pulmonary cells, study authors found a specific point mutation involving FOXF1 at the S52F DNA binding location of FOXF1’s nuclear protein. The mutation blocked molecular signaling to multiple downstream target genes involved in formation of pulmonary blood vessels.

They also discovered that the S52F FOXF1 mutant protein did not interact with a protein called STAT3. The link is critical to stimulating the development of blood vessels in the neonatal lung. This led to a deficiency of STAT3 in developing lungs and improper formation of the pulmonary circulatory system.

Researchers also found STAT3 deficiency in donated samples from ACDMPV patients who had specific point mutations in the FOXF1 gene. The authors theorized that treating newborn mice with STAT3 would stimulate blood vessel development in the lungs, but they had to figure out how to get the protein to the lungs.

STAT3 Nanoparticle Solution

Researchers turned to nanoparticle technology to deliver a STAT3 mini-gene to lungs of newborn mice. They created a novel formulation for what are known as polyethylenimine (PEI) nanoparticles.

The gelatin-like PEI nanoparticles can carry therapeutic genetic material to different parts of the body by administering them to patients intravenously. Different formulations of PEI nanoparticles are currently being tested in clinical trials for adult cancer at other institutions, according to study authors.

Therapeutic administration of STAT3 DNA to newborn mice with the S52F FOXF1 mutation restored the ability of endothelial cells to form pulmonary blood vessels. This stimulated blood vessel growth in the animals and the formation of air sacs called alveolar.

“If the efficacy of PEI nanoparticles is confirmed in the clinical trials under way for adult cancer, PEI could be considered for STAT3 gene therapy in infants with ACDMPV,” Kalinichenko said. “Considering that ACDMPV is a rare disease, a multicenter clinical trial would be needed to assess the efficacy of STAT3 gene therapy in ACDMPV newborns and infants.”

The study’s first author is Arun Pradhan, PhD, a researcher who works in the Kalinichenko laboratory.

Funding support for the study came from the National Institutes of Health (HL84151, HL141174, HL123490, HL137203, HL132849 and grants from the National Organization for Rare Disorders.

Summary Source: ScienceDaily, 19 June 2019. http://www.sciencedaily.com/releases/2019/06/190619094849.htm


Additional reference: Medical Daily, 20 June 2019. https://www.medicaldaily.com/gene-editing-offers-treatment-deadly-disease-turns-babies-blue-437090

    • Clinical, Histopathological, and Molecular Diagnostics in Lethal Lung Developmental Disorders.
      Vincent M, Karolak JA, Deutsch G, Gambin T, Popek E, Isidor B, Szafranski P, Le Caignec C, Stankiewicz P. (2019): In: Am J Respir Crit Care Med. 2019 Jun 12. doi: 10.1164/rccm.201903-0495TR. [Epub ahead of print]
      https://www.ncbi.nlm.nih.gov/pubmed/31189067

The research team examined a series of pediatric lethal lung developmental disorders, including (1) ACDMPV, (2) acinar dysplasia (AcDys), (3) congenital alveolar dysplasia (CAD), and (4) other unspecified primary pulmonary hypoplasias. The team reviewed histopathological samples from lung biopsy or autopsy. The histopathological continuum in these lethal developmental disorders has made accurate diagnosis challenging. Over the past decade, genetic studies have revealed the causative role of the FOXF1 gene or other nearby variants in chromosome 16 for ACDMPV patients. In contrast, the molecular bases of two of the other lethal lung development disorders, AcDys and CAD, have remained poorly understood but the article discusses recent progress for these other disorders, including disruption of the TBX4-FGF10-FGFR2 pathway. The team proposes that for a more precise diagnosis of lethal lung developmental disorders such as AcDys and CAD, a diagnostic pathway including whole genome sequencing should be implemented.

    • Alveolar capillary dysplasia associated with intestinal malrotation and annular pancreas due to a mutation in the FOXF1 gene: case report.
      D, Granda & F, Aguinaga & S, Przemyslaw & P, Pontn & F, Vÿsconez & H, Garz & F, Mac­as & G, Moreta & P, Stankiewicz & L, Gordillo & P, Cortez & P, Astudillo & E, Carrin-Jaramillo (2019): In: International Journal of Pregnancy & Child Birth. 5. 10.15406/ipcb.2019.05.00139. https://www.researchgate.net
    • Novel parent-of-origin-specific differentially methylated loci on chromosome 16.
      Schulze KV, Szafranski P, Lesmana H, Hopkin RJ, Hamvas A, Wambach JA, Shinawi M, Zapata G, Carvalho CMB, Liu Q, Karolak JA, Lupski JR, Hanchard NA, Stankiewicz P. (2019): Clin Epigenetics. 2019 Apr 8;11(1):60. doi: 10.1186/s13148-019-0655-8.
      https://www.ncbi.nlm.nih.gov/pubmed/30961659
    • Complex Compound Inheritance of Lethal Lung Developmental Disorders Due to Disruption of the TBX-FGF Pathway.
      Karolak JA, Vincent M, Deutsch G, Gambin T, Cogné B, Pichon O, Vetrini F, Mefford HC, Dines JN, Golden-Grant K, Dipple K, Freed AS, Leppig KA, Dishop M, Mowat D, Bennetts B, Gifford AJ, Weber MA, Lee AF, Boerkoel CF, Bartell TM, Ward-Melver C, Besnard T, Petit F, Bache I, Tümer Z, Denis-Musquer M, Joubert M, Martinovic J, Bénéteau C, Molin A, Carles D, André G, Bieth E, Chassaing N, Devisme L, Chalabreysse L, Pasquier L, Secq V, Don M, Orsaria M, Missirian C, Mortreux J, Sanlaville D, Pons L, Küry S, Bézieau S, Liet JM, Joram N, Bihouée T, Scott DA, Brown CW, Scaglia F, Tsai AC, Grange DK, Phillips JA 3rd, Pfotenhauer JP, Jhangiani SN, Gonzaga-Jauregui CG, Chung WK, Schauer GM, Lipson MH, Mercer CL, van Haeringen A, Liu Q, Popek E, Coban Akdemir ZH, Lupski JR, Szafranski P, Isidor B, Le Caignec C, Stankiewicz P. (2019): Am J Hum Genet. 2019 Feb 7;104(2):213-228. doi: 10.1016/j.ajhg.2018.12.010. Epub 2019 Jan 10. https://www.ncbi.nlm.nih.gov/pubmed/30639323

2018

    • LINE- and Alu-containing genomic instability hotspot at 16q24.1 associated with recurrent and nonrecurrent CNV deletions causative for ACDMPV.
      Szafranski P, Kośmider E, Liu Q, Karolak JA, Currie L, Parkash S, Kahler SG, Roeder E, Littlejohn RO, DeNapoli TS, Shardonofsky FR, Henderson C, Powers G, Poisson V, Bérubé D, Oligny L, Michaud JL, Janssens S, De Coen K, Van Dorpe J, Dheedene A, Harting MT, Weaver MD, Khan AM, Tatevian N, Wambach J, Gibbs KA, Popek E, Gambin A, Stankiewicz P. (2018): In: Hum Mutat. 2018 Dec;39(12):1916-1925. doi: 10.1002/humu.23608. Epub 2018 Aug 22.
      https://www.ncbi.nlm.nih.gov/pubmed/30084155

This paper shows the genomic structures predisposing the FOXF1 locus to DNA breaks, resulting in pathogenic deletions and ACDMPV.

    • Two patients with FOXF1 mutations with alveolar capillary dysplasia with misalignment of pulmonary veins and other malformations: Two different presentations and outcomes.
      Abu-El-Haija A, Fineman J, Connolly AJ, Murali P, Judge LM, Slavotinek AM. (2018): In: Am J Med Genet A. 2018 Dec;176(12):2877-2881. doi: 10.1002/ajmg.a.40641. Epub 2018 Oct 31.
      https://www.ncbi.nlm.nih.gov/pubmed/30380203
    • Alveolar capillary dysplasia with misalignment of the pulmonary veins: clinical, histological, and genetic aspects.
      Slot E, Edel G, Cutz E, van Heijst A, Post M, Schnater M, Wijnen R, Tibboel D, Rottier R, de Klein A. (2018): In: Pulm Circ. 2018 Jul-Sep;8(3):2045894018795143. doi: 10.1177/2045894018795143. Epub 2018 Jul 30.
      https://www.ncbi.nlm.nih.gov/pubmed/30058937pdficon_small *FREE – Full Article*

This paper provides an overview of the clinical aspects of ACDMPV, including guidance for clinicians, and reviews the ongoing research into the complex molecular mechanism causing ACDMPV.

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2017

    • Transcription Factors Regulating Embryonic Development of Pulmonary Vasculature
      Bolte C, Whitsett JA, Kalin TV, Kalinichenko VV (2017): In: Adv Anat Embryol Cell Biol. 2018;228:1-20. doi: 10.1007/978-3-319-68483-3_1.
      https://www.ncbi.nlm.nih.gov/pubmed/29288383
    • Use of Exome Sequencing for Infants in Intensive Care Units: Ascertainment of Severe Single-Gene Disorders and Effect on Medical Management.
      Meng L, Pammi M, Saronwala A, Magoulas P, Ghazi AR, Vetrini F, Zhang J, He W, Dharmadhikari AV, Qu C, Ward P, Braxton A, Narayanan S, Ge X, Tokita M, Santiago-Sim T, Dai H, Chiang T, Smith H, Azamian MS, Robak L, Bostwick BL, Schaaf CP, Potocki L, Scaglia F, Bacino CA, Hanchard NA, Wangler MF, Scott D, Brown C, Hu J, Belmont JW, Burrage LC, Graham BH, Sutton VR, Craigen WJ, Plon SE, Lupski JR, Beaudet AL, Gibbs RA, Muzny DM, Miller MJ, Wang X, Leduc MS, Xiao R, Liu P, Shaw C, Walkiewicz M, Bi W, Xia F, Lee B, Eng CM, Yang Y, Lalani SR. (2017): In: JAMA Pediatr. 2017 Dec 4;171(12):e173438. doi: 10.1001/jamapediatrics.2017.3438. Epub 2017 Dec 4.
      https://www.ncbi.nlm.nih.gov/pubmed/28973083pdficon_small *FREE – Full Article*
    • Infants with Atypical Presentations of Alveolar Capillary Dysplasia with Misalignment of the Pulmonary Veins Who Underwent Bilateral Lung Transplantation
      Towe CT, White FV, Grady RM, Sweet SC, Eghtesady P, Wegner DJ, Sen P, Szafranski P, Stankiewicz P, Hamvas A, Cole FS, Wambach JA (2017): In: J Pediatr. 2017 Nov 30. pii: S0022-3476(17)31375-6. doi: 10.1016/j.jpeds.2017.10.026.
      https://www.ncbi.nlm.nih.gov/pubmed/29198536

This study reviewed clinical history, diagnostic studies, explant histology, genetic sequence results, and post-transplant course for 6 infants with atypical ACDMPV who underwent bilateral lung transplantation at St. Louis Children’s Hospital. Their histology was compared with infants with classic ACDMPV and the researchers also compared their outcomes with infants transplanted for other indications. Unlike in classic ACDMPV, histopathologic findings were not distributed uniformly and were not diffuse. Lung explants from infants with atypical ACDMPV demonstrated diagnostic but nonuniform histopathologic findings. Bilateral lung transplantation was performed at 4-20 months of age. Three transplanted children are alive at 5-16 years of age, similar to outcomes for infants transplanted for other indications. The 1- and 5-year survival rates for infants with atypical ACDMPV are similar to infants transplanted for other indications.

    • Pediatric lung transplantation
      Bryant R 3rd, Morales D, Schecter M. (2017): In: Semin Pediatr Surg. 2017 Aug;26(4):213-216. doi: 10.1053/j.sempedsurg.2017.07.005. Epub 2017 Jul 25.
      https://www.ncbi.nlm.nih.gov/pubmed/28964476

This review will familiarize the reader with the current indications for transplant and the referral and listing process. The current state of lung assist devices as a bridge to pediatric lung transplantation is discussed in addition to the technical aspects of the transplant procedure. Finally, posttransplant outcomes, including anticipated morbidity and the role of retransplantation, are clarified.

    • CRISPR/Cas9-mediated deletion of lncRNA Gm26878 in the distant Foxf1 enhancer region
      Szafranski P, Karolak JA, Lanza D, Gajęcka M, Heaney J, Stankiewicz P. (2017): In: Mamm Genome. 2017 Aug;28(7-8):275-282. doi: 10.1007/s00335-017-9686-7. Epub 2017 Apr 12.
      https://www.ncbi.nlm.nih.gov/pubmed/28405742
    • Maternal mutations of FOXF1 cause alveolar capillary dysplasia despite not being imprinted
      Alsina Casanova M, Monteagudo-Sánchez A, Rodiguez Guerineau L, Court F, Gazquez Serrano I, Martorell L, Rovira Zurriaga C, Moore GE, Ishida M, Castañon M, Moliner Calderon E, Monk D, Moreno Hernando J. (2017): In: Hum Mutat. 2017 Jun;38(6):615-620. doi: 10.1002/humu.23213. Epub 2017 Mar 24.
      https://www.ncbi.nlm.nih.gov/pubmed/28256047

This paper from a team at Barcelona University, Spain focuses on imprinting in ACDMPV. We define paternal imprinting in the ACDA genetics guide as ‘the inactivation of a copy of a gene inherited from the father of an infant so that the gene is silent and not expressed. This leaves only the gene copy inherited from the infant’s mother active and expressed.’

We know that around 90% of mutations and 95% of deletions of FOXF1 are on the chromosome the infant inherited from his/her mother. It has thus been presumed that FOXF1 is subject to paternal imprinting (of course the majority of FOXF1 abnormalities arise de novo in the process of egg formation and are thus not actually inherited from the mother). However, there have been some findings that have been inconsistent with imprinting. Two prior cases of ACDMPV (both a familial case and a de novo case) have been described which were caused by FOXF1 mutations inherited from the infants’ fathers. Additionally 4 children have been identified who do not have ACDMPV but in whom both copies of chromosome 16 (in which FOXF1 is found) have been inherited from their fathers. If FOXF1 is subject to paternal imprinting this should have resulted in ACDMPV but this was not the case.

The authors of this paper thus investigate imprinting by studying 3 infants with ACDMPV, two identical twins and a separate infant. They found all 3 infants to have FOXF1 mutations that were derived from their mothers. However they then analysed the expression of FOXF1 in a variety of adult and foetal tissues and found that the genes derived from both mother and father were expressed in these tissues. They went on to study FOXF1 methylation. This is the process in which methyl groups are added to genes in order to switch them off. It is a key feature of imprinting. They found no methylation of FOXF1.

The authors conclude that the clinical and genetic data to date do not support the long-held view that FOXF1 is subject to paternal imprinting. They suggest an alternative, currently unknown mechanism is responsible for the maternal inheritance pattern of FOXF1 gene abnormalities. Thanks to Dr. Simon Ashwell, father to David, for this summary.

    • Antenatal Gastrointestinal Anomalies in Neonates Subsequently Found to Have Alveolar Capillary Dysplasia.
      Goel D, Oei JL, Lui K, Ward M, Shand AW, Mowat D, Gifford AJ, Loo C. (2017): In: Clin Case Rep. 2017 Mar 13;5(5):559-566. doi: 10.1002/ccr3.888. eCollection 2017 May.
      https://www.ncbi.nlm.nih.gov/pubmed/28469849pdficon_small *FREE – Full Article*
    • A Novel De Novo Pathogenic Variant in FOXF1 in a Newborn with Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins.
      Ma Y, Jang M, Yoo HS, Ahn SY, Sung SI, Chang YS, Ki CS, Park WS. (2017): In: Yonsei Med J. 2017 May;58(3):672-675. doi: 10.3349/ymj.2017.58.3.672.
      https://www.ncbi.nlm.nih.gov/pubmed/28332379pdficon_small *FREE – Full Article*
    • The Role of Serotonin Transporter in Human Lung Development and in Neonatal Lung Disorders.
      Castro EC, Sen P, Parks WT, Langston C, Galambos C. (2017): In: Can Respir J. 2017;2017:9064046. doi: 10.1155/2017/9064046. Epub 2017 Feb 20.
      https://www.ncbi.nlm.nih.gov/pubmed/28316463pdficon_small *FREE – Full Article*

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2016

    • Alveolar capillary dysplasia with misalignment of the pulmonary veins due to novel insertion mutation of FOXF1
      Nagano N, Yoshikawa K, Hosono S, Takahashi S, Nakayama T. (2016): In: Pediatr Int. 2016 Dec;58(12):1371-1372. doi: 10.1111/ped.13107.
      https://www.ncbi.nlm.nih.gov/pubmed/28008732
    • Fetal-MRI prenatal diagnosis of severe bilateral lung hypoplasia: alveolar capillary dysplasia case report
      Salvatore Zirpoli, Alice Marianna Munari, Mariangela Rustico, Gaetano Bulfamante, Gianluca Lista, Luigina Spaccini, and Claudia Cesaretti. (2016): In: J Prenat Med. 2016 Jul-Dec; 10(3-4): 15–19. doi: 10.11138/jpm/2016.10.3.015
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505476/pdficon_small *FREE – Full Article*

This is a case study in Italy of a 36-week pregnant woman that had second level prenatal testing after a routine ultrasound indicated possible heart and thorax issues. A prenatal echocardiography found no heart issues but an MRI identified small lung volume with decreased lung signal intensity. The family was counseled regarding a fatal prognosis. After birth, a chest X-ray showed bilateral pneumothorax with reduced and poorly ventilated lungs. An autopsy showed characteristics of ACDMPV; FOXF1 genetic testing was not performed. The authors believe prenatal testing measuring fluid lung volume (FLV) through MRI and Ultrasound, together with MRI lung signal intensity assessment, may help prenatally confirm or quantity the degree of lung underdevelopment. This summary prepared by Eliza Rista.

    • Clinical utility of array comparative genomic hybridisation in prenatal setting
      Lovrecic L, Remec ZI, Volk M, Rudolf G, Writzl K, Peterlin B. (2016): In: BMC Med Genet. 2016 Nov 15;17(1):81.
      https://www.ncbi.nlm.nih.gov/pubmed/27846804
    • Risk and relevance of open lung biopsy in pediatric ECMO patients: the Dutch experience
      Houmes RJ, Ten Kate CA, Wildschut ED, Verdijk RM, Wijnen RM, de Blaauw I, Tibboel D, van Heijst AF. (2016): In: J Pediatr Surg. 2016 Nov 14. pii: S0022-3468(16)30564-4. doi: 10.1016/j.jpedsurg.2016.11.031
      https://www.ncbi.nlm.nih.gov/pubmed/27894766
    • Lethal lung hypoplasia and vascular defects in mice with conditional Foxf1 overexpression
      Dharmadhikari AV, Sun JJ, Gogolewski K, Carofino BL, Ustiyan V, Hill M, Majewski T, Szafranski P, Justice MJ, Ray RS, Dickinson ME, Kalinichenko VV, Gambin A, Stankiewicz P. (2016): In: Biol Open. 2016 Sep 16. pii: bio.019208. doi: 10.1242/bio.019208. [Epub ahead of print].
      https://www.ncbi.nlm.nih.gov/pubmed/27638768pdficon_small *FREE – Full Article*

The genetic research team at Baylor College of Medicine in Houston, Texas, USA has worked in direct collaboration with a developmental biology research group at Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio, USA, including recently publishing together a mouse model of FOXF1 overexpression. The full manuscript entitled “Lethal lung hypoplasia and vascular defects in mice with conditional Foxf1 overexpression” as published in Biology Open can be found HERE. The paper was based off the PhD thesis of Avinash Dharmadhikari, a graduate student and mentee of Dr. Pawel Stankiewicz at Baylor and used mouse models to research what happens in mice when the FOXF1 gene is overexpressed. The research was a significant amount of work involving substantial experimentation with mice and follows up on prior work discussed in a 2014 paper. The 2014 study investigated the outcomes of FOXF1 duplication where four unrelated living people with duplication of FOXF1 were identified. Unexpectedly, none of the four patients had any lung abnormalities. However, Baylor was unable to measure the expression levels of FOXF1 in the 2014 study because the patients were otherwise healthy with regards to respiratory issues so no lung biopsies could be performed. As such, in the 2016 paper, Baylor implemented a mouse model study to increase the availability of samples in which to study FOXF1 expression levels. They developed a conditional model to switch on FOXF1 when they want in mice to change the expression levels and observed lung abnormalities when FOXF1 was overexpressed. Similar to FOXF1 loss, FOXF1 overexpression in mice is lethal. Based on the results of the 2016 mouse models, the research concluded that to be on the safe side, any future gene therapy would need to be careful with manipulating the expression of FOXF1 gene in humans because it could be problematic in humans if FOXF1 is overexpressed too much. This has important clinical implications when considering potential gene therapy approaches to treat disorders of FOXF1 abnormal dosage, such as ACDMPV.

ACDMPV was also mentioned in an article about research being conducted by the Cincinnati group referenced above (click HERE). The research is currently only applicable in mouse models and considerable further research is needed as to how the compound would apply to human lung diseases. From the article, “Researchers are developing a new drug to treat life-threatening lung damage and breathing problems in people with severe infections like pneumonia, those undergoing certain cancer treatments and premature infants with underdeveloped, injury prone lungs…Two laboratories at Cincinnati Children’s are developing a pharmacologic compound that in mouse models stimulates FOXF1 and promotes repair after lung injury.” The ACDA is hopeful for additional research that provides a full understanding of the molecular mechanism as to how the compound works and then further research into whether this could ever be applied to human patients at some point in the future.

The ACDA is grateful for the continued collaborative efforts between the research teams at Baylor and Cincinnati Children’s. This summary prepared by Eliza Rista.

    • FOXF1 gene mutation in alveolar capillary dysplasia associated with Hirschsprung’s disease and clinical review.
      Goel D, Oei JL, Shand AW, Mowat D, Loo C. (2016): In: J Paediatr Child Health. 2016 Jul;52(7):787-8. doi: 10.1111/jpc.13191.
      http://www.ncbi.nlm.nih.gov/pubmed/27439648
    • Diffuse lung disease: cause of persistent pulmonary hypertension before one year of age
      [Article in Spanish] Dicembrino M, Haag D, Álvarez M, Díaz Cazaux A, Castaños C. (2016): In: Arch Argent Pediatr. 2016 Jun 1;114(3):e175-e178. doi: 10.5546/aap.2016.e108. Epub 2016 Jun 1.
      http://www.ncbi.nlm.nih.gov/pubmed/27164352
    • Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins
      Szafranski P, Gambin T, Dharmadhikari AV, Akdemir KC, Jhangiani SN, Schuette J, Godiwala N, Yatsenko SA, Sebastian J, Madan-Khetarpal S, Surti U, Abellar RG, Bateman DA, Wilson AL, Markham MH, Slamon J, Santos-Simarro F, Palomares M, Nevado J, Lapunzina P, Chung BH, Wong WL, Chu YW, Mok GT, Kerem E, Reiter J, Ambalavanan N, Anderson SA, Kelly DR, Shieh J, Rosenthal TC, Scheible K, Steiner L, Iqbal MA, McKinnon ML, Hamilton SJ, Schlade-Bartusiak K, English D, Hendson G, Roeder ER, DeNapoli TS, Littlejohn RO, Wolff DJ, Wagner CL, Yeung A, Francis D, Fiorino EK, Edelman M, Fox J, Hayes DA, Janssens S, De Baere E, Menten B, Loccufier A, Vanwalleghem L, Moerman P, Sznajer Y, Lay AS, Kussmann JL, Chawla J, Payton DJ, Phillips GE, Brosens E, Tibboel D, de Klein A, Maystadt I, Fisher R, Sebire N, Male A, Chopra M, Pinner J, Malcolm G, Peters G, Arbuckle S, Lees M, Mead Z, Quarrell O, Sayers R, Owens M, Shaw-Smith C, Lioy J, McKay E, de Leeuw N, Feenstra I, Spruijt L, Elmslie F, Thiruchelvam T, Bacino C, Langston C, Lupski JR, Sen P, Popek E, Stankiewicz P. (2016): In: Hum Genet. May 2016.
      http://www.ncbi.nlm.nih.gov/pubmed/27071622

This paper updates current knowledge about the genetics of ACDMPV based upon past research and new findings from recent work. Baylor College of Medicine in Houston, Texas, USA has accumulated the largest collection of ACDMPV samples worldwide (N=141 families), in which they have identified 86 pathogenic variants in the FOXF1 locus: 38 deletion CNVs, a complex rearrangement and 47 point mutations. DNA was not of sufficient quality for genetic testing in most of the remaining 55 families. The paper demonstrates the complexity of genomic and epigenetic regulation of the FOXF1 gene in 16q24.1. This summary prepared by Eliza Rista.

    • Long-range enhancers modulate Foxf1 transcription in blood vessels of pulmonary vascular network
      Seo H, Kim J, Park GH, Kim Y, Cho SW. (2016): In: Histochem Cell Biol. 2016 May 11 [Epub ahead of print]
      http://www.ncbi.nlm.nih.gov/pubmed/27166834
    • Variable phenotypic presentation of a novel FOXF1 missense mutation in a single family
      Reiter J, Szafranski P, Breuer O, Perles Z, Dagan T, Stankiewicz P, Kerem E. (2016): In: Pediatr Pulmonol. 2016 May 4. doi: 10.1002/ppul.23425. [Epub ahead of print]
      http://www.ncbi.nlm.nih.gov/pubmed/27145217
    • 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, Fai Man Ivan Lo. (2016): In: American Journal of Medical Genetics Part A. Version of Record online: 25 APR 2016. DOI: 10.1002/ajmg.a.37660
      http://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.37660/abstract
    • Unraveling the role of genomic imprinting at 16q24.1 in pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins and maternal uniparental disomy 16
      Paweł Stankiewicz, Avinash V Dharmadhikari, Jenny J Sun, Brandi Carofino, Kadir Caner Akdemir, Claire Langston, Edwina Popek, Monica J Justice, Mary E Dickinson, Russell Ray, Partha Sen, Przemyslaw Szafranski
      Abstracts of the 13th International Congress of Human Genetics (ICHG2016), Kyoto, Japan, 3-7 April 2016
      http://www.ichg2016.org/pdficon_small *FREE – Abstract*
    • Recommendations for utilization of the paracorporeal lung assist device in neonates and young children with pulmonary hypertension
      Gazit AZ, Sweet SC, Grady RM, Boston US, Huddleston CB, Hoganson DM, Shepard M, Raithel S, Mehegan M, Doctor A, Spinella PC, Eghtesady P. (2016): In: Pediatr Transplant. 2016 Mar;20(2):256-70. doi: 10.1111/petr.12673. Epub 2016 Feb 21.
      http://www.ncbi.nlm.nih.gov/pubmed/26899454
    • Clinical case of the course of congenital alveolar-capillary dysplasia of the lungs at a newborn
      [Article in Russian] Gavrilova E.S.; Borisova А.А.; Bykova Е.М.; Pozgalyova N.V.; Panina O.S.; Chernenkov Yu.V. (2016): In: Saratovskij Naučno-medicinskij Žurnal, Volume 12, Number 2, 2016, pp. 162-164(3)
      http://www.ingentaconnect.com/content/doaj/19950039/2016/00000012/00000002/art00012pdficon_small *FREE – Full Article*

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2015

    • Prenatal Diagnosis of Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins
      Prothro SL, Plosa E, Markham M, Szafranski P, Stankiewicz P, Killen SA. (2015): In: J Pediatr. 2015 Dec 15. pii: S0022-3476(15)01453-5. doi: 10.1016/j.jpeds.2015.11.041.
      http://www.ncbi.nlm.nih.gov/pubmed/26703872
    • Alveolar Capillary Dysplasia as a Cause of Persistent Pulmonary Hypertension
      Razak A, Mohanty PK, Nagesh NK. (2015): In: Indian Pediatr. 2015 Nov 11;52(11):984-6.
      http://www.ncbi.nlm.nih.gov/pubmed/26615352pdficon_small *FREE – Full Article*
    • Diffuse pulmonary development disorders- Molecular definable causes of pulmonary hypertension in the mature newborn
      Meike Hengst, Nicolaus Schwerk, Jost Wigand Richter, Hans Fuchs, Lars Welzing, Mathias Klemme, Matthias Griese. (2015): In: European Respiratory Journal, 1 September 2015
      http://erj.ersjournals.com/content/46/suppl_59/PA1867
    • P3-22 Prenatal diagnosis of alveolar capillary dysplasia with misalignment of the pulmonary veins
      Jill Nichols, Mary Carroll, Vanderbilt University Medical Center, Nashville, Tennessee, United States
      Poster Abstracts of the ISPD 19th International Conference on Prenatal Diagnosis and Therapy, Washington, DC, USA, 12–15 July 2015
      http://onlinelibrary.wiley.com/doi/10.1002/pd.4617/fullpdficon_small *FREE – Full Article*

ACDMPV was part of the poster session for the 19th “International Conference on Prenatal Diagnosis and Therapy” in Washington, DC, USA on July 12-15, 2015. Vanderbilt University Medical Center prepared a poster based on an experience with a prenatal diagnosis of ACDMPV. A mother had a CVS due to concerns viewed on an ultrasound in the first trimester (cystic hygroma and echogenic bowel) and microarray analysis was done, which detected a deletion in the FOXF1 region. The family received counseling on ACDMPV and the baby was delivered at 39 weeks and unfortunately did not survive past the second day. This work is significant because according to the abstract, “This is the first reported prenatal diagnosis of ACDMPV devoid of a family history.” This summary prepared by Eliza Rista.

    • Does paternal imprinting of FOXF1 on 16q24.1 explain the maternal UPD(16) phenotype?
      A. V. Dharmadhikar, B. Carofino, J. J. Sun, P. Szafranski, R. Ray, M. J. Justice, M. E. Dickinson, P. Stankiewicz
      (C07.1) Abstracts of the European Society of Human Genetics (ESHG2015) European Human Genetics Conference, Glasgow, Scotland, United Kingdom, 6-9 June 2015
      https://www.eshg.orgpdficon_small *FREE – Abstract* and pdficon_small *FREE – Presentation Materials*
    • A late presenter and long-term survivor of alveolar capillary dysplasia with misalignment of the pulmonary veins
      Yukie Ito, Takuma Akimoto, Kazutoshi Cho, Masafumi Yamada, Mishie Tanino, Tomoyuki Dobata, Masanori Kitaichi, Satoru Kumaki, Yoshikazu Kinugawa (2015): In: European Journal of Pediatrics, April 2015
      http://link.springer.com/article/10.1007%2Fs00431-015-2543-3

This is a review article, summarizing recent studies of FOXF1. It discusses where in the body the FOXF1 gene is expressed in humans and mice, the effects on mice who have the FOXF1 gene removed, the effects of duplication of FOXF1 and FOXF1 and cancer. Of relevance to ACDMPV parents, the authors point out that in ACDMPV-affected infants, 44 mutations involving FOXF1 and 36 deletions involving FOXF1 or upstream of FOXF1 have been reported thus far. In infants with ACDMPV for whom it was possible to determine from which parent a deletion arose, in all 24 they arose de novo on the maternal chromosome, consistent with the understanding the FOXF1 is paternally imprinted in human lungs.  Thanks to Dr. Simon Ashwell, father to David, for this summary.

    • Intrapulmonary vascular shunt pathways in alveolar capillary dysplasia with misalignment of pulmonary veins
      Galambos C, Sims-Lucas S, Ali N, Gien J, Dishop MK, Abman SH. (2015): In: Thorax. 2015 Jan;70(1):84-5. doi: 10.1136/thoraxjnl-2014-205851. Epub 2014 Jul 21.
      http://www.ncbi.nlm.nih.gov/pubmed/25052575 pdficon_small *FREE – Full Article*
    • A novel FOXF1 mutation associated with alveolar capillary dysplasia and coexisting colobomas and hemihyperplasia
      G C Geddes, D P Dimmock, D A Hehir, D C Helbling, E Kirkpatrick, R Loomba, J Southern, M Waknitz, G Scharer, and G G Konduri, (2015): In: Journal of Perinatology (2015) 35, 155–157. doi:10.1038/jp.2014.187.
      http://www.nature.com/jp/journal/v35/n2/abs/jp2014187a.html
    • Recurrence of alveolar capillary dysplasia with misalignment of pulmonary veins in two consecutive siblings
      Gabriel Nuncio Benevides, Patrícia Picciarelli de Lima, Aloisio Felipe-Silva, Silvana Maria Lovisolo, Ana Maria Andrello Gonçalves Pereira de Melo (2015): In: Autopsy & Case Reports, Hospital Universitário da Universidade de São Paulo, Vol 5, No 1 (2015).
      http://www.autopsyandcasereports.org/ojs/index.php/autopsy/article/view/356 pdficon_small *FREE – Full Article*
    • Dysplasie alvéolo-capillaire avec mésalignement des veines pulmonaires : une cause de cyanose néonatale réfractaire létale
      B. Savey, C. Jeanne-Pasquier, P. Dupont-Chauvet, P. Maragnes, A. Bellot, B. Guillois (2015): In: Archives de Pédiatrie, Volume 22, Issue 2, Pages 185-190.
      http://europepmc.org/abstract/med/25497366

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2014

    • Molecular and clinical analyses of 16q24.1 duplications involving FOXF1 identify an evolutionarily unstable large minisatellite.
      Dharmadhikari AV, Gambin T, Szafranski P, Cao W, Probst FJ, Jin W, Fang P, Gogolewski K, Gambin A, George-Abraham JK, Golla S, Boidein F, Duban-Bedu B, Delobel B, Andrieux J, Becker K, Holinski-Feder E, Cheung SW, Stankiewicz P. (2014): In: BMC Med Genet. 2014 Dec 4;15:128. doi: 10.1186/s12881-014-0128-z.
      http://www.ncbi.nlm.nih.gov/pubmed/25472632 pdficon_small *FREE – Full Article*

Mutations or deletions of the FOXF1 gene cause ACDMPV. The effects of, in effect the opposite, duplications of FOXF1 are unknown. This study investigated the outcomes of FOXF1 duplication. Four unrelated people with duplication of FOXF1 were identified. The first, a 4 1⁄2 year old boy has speech delay, behavioral issues and facial changes but he also has a further genetic abnormality that may account for these. The second, a 13 year old boy, has autism, behavioral problems and limited growth. He has two other genetic abnormalities that again may account for some of these issues. The third patient, an adult, has pyloric stenosis and other gut abnormalities. She has a daughter with similar gut abnormalities to whom she has passed the FOXF1 duplication. The fourth is a 10 1⁄2 year old boy with speech and motor delay and mild learning difficulties.

None of the four have any lung abnormalities. All four have duplications of FOXF1. The first three patients inherited the duplication from healthy fathers. This is consistent with the previous evidence that FOXF1 is paternally imprinted, i.e. the gene inherited from the father is inactive; only the gene inherited from a mother is expressed. However, the third patient inherited the FOXF1 duplication from a healthy father suggesting that FOXF1 is paternally imprinted in the lungs only, as she had gut abnormalities. In the fourth patient, the duplication arose de novo on the maternal chromosome.

The study shows that duplication of FOXF1 does not cause any lung abnormalities but can cause gut abnormalities. Thanks to Dr. Simon Ashwell, father to David, for this summary.

    • Alveolar capillary dysplasia with misalignment of the pulmonary veins associated with aortic coarctation and intestinal malrotation
      Arreo Del Val V, Avila-Alvarez A, Schteffer LR, Santos F, Deiros L, Del Cerro MJ (2014): In: J Perinatol. 2014 Oct;34(10):795-7. doi: 10.1038/jp.2014.94.
      http://www.ncbi.nlm.nih.gov/pubmed/25263726
    • FOXF1 Transcription Factor Is Required for Formation of Embryonic Vasculature by Regulating VEGF Signaling in Endothelial Cells
      Ren X, Ustiyan V, Pradhan A, Cai Y, Havrilak JA, Bolte CS, Shannon JM, Kalin TV, Kalinichenko VV. (2014): In: Circ Res. 2014 Sep 26;115(8):709-20. doi: 10.1161/CIRCRESAHA.115.304382. Epub 2014 Aug 4.
      http://www.ncbi.nlm.nih.gov/pubmed/25091710 pdficon_small *FREE – Full Article*
    • Rapidly Fatal “Congenital Lung Dysplasia”: A Case Report and Review of the Literature
      Don M, Orsaria M, Da Dalt E, Tringali C, Sacher B. (2014): In: Fetal Pediatr Pathol. 2014 Apr;33(2):109-13. doi: 10.3109/15513815.2013.878009. Epub 2014 Jan 28
      https://www.ncbi.nlm.nih.gov/pubmed/24467188 pdficon_small *FREE – Full Article*

“Congenital lung dysplasia” groups three pediatric lung diseases, including acinar dysplasia (AD), congenital alveolar dysplasia (CAD) and alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). This article discusses an overview of this spectrum of diseases. Summary prepared by Eliza Rista.

    • Parental somatic mosaicism is underrecognized and influences recurrence risk of genomic disorders.
      Campbell IM, Yuan B, Robberecht C, Pfundt R, Szafranski P, McEntagart ME, Nagamani SC, Erez A, Bartnik M, Wiśniowiecka-Kowalnik B, Plunkett KS, Pursley AN, Kang SH, Bi W, Lalani SR, Bacino CA, Vast M, Marks K, Patton M, Olofsson P, Patel A, Veltman JA, Cheung SW, Shaw CA, Vissers LE, Vermeesch JR, Lupski JR, Stankiewicz P. (2014): In: Am J Hum Genet. 2014 Aug 7;95(2):173-82. doi: 10.1016/j.ajhg.2014.07.003. Epub 2014 Jul 31.
      http://www.ncbi.nlm.nih.gov/pubmed/25087610 pdficon_small *FREE – Full Article*

This research, performed by Professor Pawel Stankiewicz’s group at Baylor, investigated the issue of somatic mosaicism in the transmission of genetic diseases. Somatic mosaicism describes the situation where an individual has more than one type of genetic material in their body (eg both normal and abnormal copies of a gene). This arises due to mutations as our cells divide.

Conventional genetic tests often fail to find somatic mosaicism as it is often low-level (sometimes <1% of DNA) and thus cannot be detected. This has resulted in children with genetic diseases from parents with apparently normal DNA being labelled incorrectly as having a new ‘de novo’ genetic abnormality.

The researchers identified 100 parental couples who had had infants with apparently de novo mutations leading to a variety of genetic conditions. Families with ACDMPV were not included in the study but its results have some relevance to the ACDMPV community.

All families had been investigated with conventional genetic testing and neither parent had been found not the carry the genetic abnormality affecting their child. The researchers then developed novel detailed techniques to look more closely in the parents’ blood DNA in the specific area of genetic abnormality that were found in their child. Using these techniques 4 parents (4%), 2 mothers and 2 fathers, were found to have somatic mosaicism that was responsible for their child inheriting the condition. The parents’ amount of mosaicism (abnormal DNA) varied from less than 1% to 9% of total DNA.

The researchers developed a computer model to explore issues around recurrence risk. They calculated that, by virtue of having had a child with an apparently de novo genetic disorder, the risk of a couple having a second affected child is approximately 0.1% (one in a thousand). The risk was much higher in parents who were found to have mosaicism detected in blood DNA than those that did not. Parents of affected infants without detectable somatic mosaicism are likely to have mosaicism limited to eggs or sperm, but testing to confirm this is currently not possible. Mothers with mosaicism (as is always the route of transmission to an infant with ACDMPV) have a higher risk of recurrence than fathers as they tend to carry a higher proportion of affected eggs vs. sperm.

The take-home message for the ACDMPV community is that the risk for a couple of having a subsequent infant with ACDMPV might be able to be predicted by testing them for somatic mosaicism. Its absence would suggest a low chance of subsequent pregnancies being affected by ACDMPV. This might help in making decisions about pre-natal testing. Importantly this requires first the identification of a FOXF1 deletion in the affected infant. The lab is unable to test for somatic mosaicism in the parents of infants with ACDMPV who have a FOXF1 mutation due to unreliability of this test at such levels.

Professor Stankiewicz tells me that the Baylor lab routinely tests for low-level somatic mosaicism in parents of infants with ACDMPV who have FOXF1 deletions. So far none of 22 tested families have demonstrated mosaicism. Thanks to Dr. Simon Ashwell, father to David, for this summary.

    • Two deletions overlapping a distant FOXF1 enhancer unravel the role of lncRNA LINC01081 in etiology of alveolar capillary dysplasia with misalignment of pulmonary veins.
      Przemyslaw Szafranski, Avinash V. Dharmadhikari, Jennifer A. Wambach, Chris T. Towe, Frances V. White, R. Mark Grady, Pirooz Eghtesady, F. Sessions Cole, Gail Deutsch, Partha Sen and Pawel Stankiewicz
      (2014): In: Am J Med Genet A. 2014 August ; 164(8): 2013–2019. doi:10.1002/ajmg.a.36606.
      http://www.ncbi.nlm.nih.gov/pubmed/24842713 pdficon_small *FREE – Full Article*
    • Hereditary interstitial lung diseases manifesting in early childhood in Japan.
      Akimoto T, Cho K, Hayasaka I, Morioka K, Kaneshi Y, Furuta I, Yamada M, Ariga T, Minakami H. (2014): In: Pediatr Res. 2014 Nov;76(5):453-8. doi: 10.1038/pr.2014.114. Epub 2014 Aug 8.
      http://www.ncbi.nlm.nih.gov/pubmed/25105258
    • Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV)—awareness prevents extended or futile ECMO use
      Ullas Angadi, Vishnuvardhan Meedimale, Simon Robinson (2014): In: Indian Journal of Thoracic and Cardiovascular Surgery, June 2014, Volume 30, Issue 2, pp 147-151
      http://link.springer.com/article/10.1007%2Fs12055-014-0291-z
    • Comparative Analyses of Lung Transcriptomes in Patients with Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins and in Foxf1 Heterozygous Knockout Mice
      Partha Sen, Avinash V. Dharmadhikari, Tadeusz Majewski, Mahmoud A. Mohammad,Tanya V. Kalin, Joanna Zabielska, Xiaomeng Ren, Molly Bray, Hannah M. Brown, Stephen Welty, Sundararajah Thevananther, Claire Langston, Przemyslaw Szafranski, Monica J. Justice, Vladimir V. Kalinichenko, Anna Gambin, John Belmont, Pawel Stankiewicz. (2014): In: PLOS ONE Vol 9 Issue 4 (April 2014)
      http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0094390 pdficon_small *FREE – Full Article*
    • The use of early lung biopsy in detection of fatal pulmonary disease in the neonate.
      Deshmukh H, Lioy J. (2014): In: J Pediatr. 2014 Apr;164(4):934-6. doi: 10.1016/j.jpeds.2013.11.035. Epub 2013 Dec 24.
      http://www.ncbi.nlm.nih.gov/pubmed/24373577
    • Alveolar capillary dysplasia with multiple congenital anomalies and bronchoscopic airway abnormalities
      V Bellamkonda-Athmaram, C G Sulman, D G Basel, J Southern, G G Konduri and M A Basir (2014): In: Journal of Perinatology (2014) 34, 326–328; doi:10.1038/jp.2013.175
      http://www.nature.com/jp/journal/v34/n4/abs/jp2013175a.html
    • FOXF1 Transcription Gene Testing in a Case of Late Presentation Alveolar Capillary Dysplasia.
      Sharon Thomas, Mudit Mathur, Thomas Bahk. (2014): In: Chest (Impact Factor: 7.13). 03/2014; 145(3 Suppl):445A. DOI: 10.1378/chest.1835561.
      http://www.researchgate.net/
    • Three-dimensional reconstruction identifies misaligned pulmonary veins as intrapulmonary shunt vessels in alveolar capillary dysplasia.
      Galambos C, Sims-Lucas S, Abman SH. (2014): In: J Pediatr. 2014 January ; 164(1): 192–195. doi:10.1016/j.jpeds.2013.08.035
      http://www.ncbi.nlm.nih.gov/pubmed/24079727 pdficon_small *FREE – Full Article*
    • Alveolar Capillary Dysplasia: A Genetically Determined Disruption Of The Alveolar/mesenchymal Cross-talk Causing Neonatal Hypoxic Failure
      C Lizama, D Peca, PE Cogo, I Stucin-Gantar, P Ursell, A Zovein, A VanHeijst, O Danhaive. (2014): In: Arch Dis Child 2014;99:A188 doi:10.1136/archdischild-2014-307384.508
      http://adc.bmj.com/content/99/Suppl_2/A188.2.abstract pdficon_small *FREE – Full Article*
    • Paracorporeal lung assist devices as a bridge to recovery or lung transplantation in neonates and young children.
      Hoganson DM, Gazit AZ, Boston US, Sweet SC, Grady RM, Huddleston CB, Eghtesady P. (2014): In: J Thorac Cardiovasc Surg. 2014 Jan;147(1):420-6. doi: 10.1016/j.jtcvs.2013.08.078. Epub 2013 Nov 4.
      http://www.ncbi.nlm.nih.gov/pubmed/24199759 pdficon_small *FREE – Full Article*

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2013

    • Novel FOXF1 deep intronic deletion causes lethal lung developmental disorder, alveolar capillary dysplasia with misalignment of pulmonary veins.
      Szafranski P1, Yang Y, Nelson MU, Bizzarro MJ, Morotti RA, Langston C, Stankiewicz P. (2013): In: Hum Mutat. 2013 Nov;34(11):1467-71. doi: 10.1002/humu.22395. Epub 2013 Sep 4.
      http://www.ncbi.nlm.nih.gov/pubmed/23943206 pdficon_small *FREE – Full Article*
    • Alveolar capillary dysplasia with misalignment of pulmonary veins with a wide spectrum of extrapulmonary manifestations.
      Nguyen L, Riley MM, Sen P, Galambos C. (2013): In: Pathol Int. 2013 Oct;63(10):519-21. doi: 10.1111/pin.12102.
      http://www.ncbi.nlm.nih.gov/pubmed/24147432
    • Alveolar capillary dysplasia with misalignment of pulmonary veins: concordance between pathological and molecular diagnosis
      Y Castilla-Fernandez, C Copons-Fernández, R Jordan-Lucas, Á Linde-Sillo, I Valenzuela-Palafoll, J C Ferreres Piñas, A Moreno-Galdó and F Castillo-Salinas. (2013): In: Journal of Perinatology 33, 401-403 (May 2013) | doi:10.1038/jp.2012.63
      http://www.nature.com/jp/journal/v33/n5/full/jp201263a.html
    • Novel FOXF1 Mutations in Sporadic and Familial Cases of Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins Imply a Role for its DNA Binding Domain
      Sen P, Yang Y, Navarro C, Silva I, Szafranski P, Kolodziejska KE, Dharmadhikari AV, Mostafa H, Kozakewich H, Kearney D, Cahill JB, Whitt M, Bilic M, Margraf L, Charles A, Goldblatt J, Gibson K, Lantz PE, Garvin AJ, Petty J, Kiblawi Z, Zuppan C, McConkie-Rosell A, McDonald MT, Peterson-Carmichael SL, Gaede JT, Shivanna B, Schady D, Friedlich PS, Hays SR, Palafoll IV, Siebers-Renelt U, Bohring A, Finn LS, Siebert JR, Galambos C, Nguyen L, Riley M, Chassaing N, Vigouroux A, Rocha G, Fernandes S, Brumbaugh J, Roberts K, Ho-Ming L, Lo IF, Lam S, Gerychova R, Jezova M, Valaskova I, Fellmann F, Afshar K, Giannoni E, Muhlethaler V, Liang J, Beckmann JS, Lioy J, Deshmukh H, Srinivasan L, Swarr DT, Sloman M, Shaw-Smith C, van Loon RL, Hagman C, Sznajer Y, Barrea C, Galant C, Detaille T, Wambach JA, Cole FS, Hamvas A, Prince LS, Diderich KE, Brooks AS, Verdijk RM, Ravindranathan H, Sugo E, Mowat D, Baker ML, Langston C, Welty S, Stankiewicz P. (2013): In: Human Mutation
      http://www.ncbi.nlm.nih.gov/pubmed/23505205 pdficon_small *FREE – Full Article*

This paper updates the publication by the same authors in 2009 in which they reported for the first time that abnormalities (mutations and deletions) in the FOXF1 gene and the area of chromosome 16 around the gene are responsible for ACDMPV. The 2009 paper found such abnormalities in 40% infants with ACDMPV. Since this publication, material has been collected from a further 47 infants. Thirty new de novo (see below) mutations in FOXF1 are described. This means that of the 93 infants with ACDMPV that Dr Sen’s group has studied 61% have been found to have a mutation in FOXF1 or a deletion around FOXF1. This confirms the role of abnormalities in the FOXF1 gene as the major cause of ACDMPV.

Two familial cases of ACDMPV are described. These confirm that FOXF1 is subject to paternal imprinting. This means that the FOXF1 gene inherited by an infant from his or her father is inactivated, but the gene inherited from the mother is active and expressed. Thus if an abnormality in FOXF1 develops in the production of an egg by a female (which occurs when she is in utero), this is expressed and will result in an infant with ACDMPV. However, if a similar abnormality occurs in the production of a sperm (by a mature man) the resulting infant will not have ACDMPV as FOXF1 is inactivated. However, the individual will be a carrier of the abnormality and can pass it on to his or her offspring. A female carrier can pass the abnormality to her children, which will result in ACDMPV.

The incidence of familial cases of ACDMPV in Dr. Sen’s combined series is approximately 2%. Dr. Sen mentions that his group is the only one in the world studying FOXF1 in relation to ACDMPV and that they operate a service to detect FOXF1 mutations and deletions pre- or post-natally on a research basis. Thanks to Dr. Simon Ashwell, father to David, for this summary.

    • Deletions In 16Q24.2 are Associated with Autism Spectrum Disorder, Intellectual Disability and Congenital Renal Malformation.
      Handrigan, Gregory Ryan; Chitayat, David; Lionel, Anath C.; Pinsk, Maury; Vaags, Andrea K.; Marshall, Christian R. et al. (2013): In: J Med Genet 50 (3), 163–73.
      http://www.ncbi.nlm.nih.gov/pubmed/23335808
    • Fox Gene Cluster Defects in Alveolar Capillary Dysplasia Associated with Congenital Heart Disease.
      Laux, Daniela; Malan, Valerie; Bajolle, Fanny; Boudjemline, Younes; Amiel, Jeanne; Bonnet, Damien (2013): In: Cardiol Young, 1–8.
      http://www.ncbi.nlm.nih.gov/pubmed/23331759
    • A Novel Mutation in FOXF1 Gene Associated with Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins, Intestinal Malrotation and Annular Pancrea
      Miranda, Joana; Rocha, Gustavo; Soares, Paulo; Morgado, Helder; Baptista, Maria Joao; Azevedo, Ines et al. (2013): In: Neonatology 103 (4), 241–245.
      http://www.ncbi.nlm.nih.gov/pubmed/23407133
    • Inversion Upstream of Foxf1 in a Case of Lethal Alveolar Capillary Dysplasia with Misalignment of Pulmonary Vein
      Parris, Toshima; Nik, Ali Moussavi; Kotecha, Sailesh; Langston, Claire; Helou, Khalil; Platt, Craig; Carlsson, Peter (2013): In: Am J Med Genet A.
      http://www.ncbi.nlm.nih.gov/pubmed/23444129

This is a report of an infant with ACDMPV in which a novel genetic abnormality is described. The abnormality was detected by karyotyping. The infant was found to have a part of chromosome 16 inverted, close to the FOXF1 gene. The paper thus adds to the list of abnormalities of chromosome 16 that can cause ACDMPV. Thanks to Dr. Simon Ashwell, father to David, for this summary.

    • Small Noncoding Differentially Methylated Copy-Number Variants, including Lncrna Genes, Cause a Lethal Lung Developmental Disorder
      Szafranski, Przemyslaw; Dharmadhikari, Avinash V.; Brosens, Erwin; Gurha, Priyatansh; Kolodziejska, Katarzyna E.; Ou, Zhishuo et al. (2013):. In: Genome Re 23 (1), 23–33.
      http://www.ncbi.nlm.nih.gov/pubmed/23034409 pdficon_small *FREE – Full Article*

Introduction
It is now well known that genetic errors (deletions and mutations) within the FOXF1 gene are responsible for some cases of ACDMPV.

It has been predicted that the FOXF1 gene is subject to paternal imprinting. This means that the FOXF1 gene inherited from the father is partially inactivated and silent, leaving only the gene inherited from the mother active and expressed. Recent work has supported this prediction.

Methods
In this study blood was taken from 9 infants with ACDMPV who did not have mutations in the FOXF1 gene. A test called comparative genomic hybridisation (CGH) was performed at 16q24.1, the area of chromosome 16 in which FOXF1 is found. CGH can detect gains or losses in DNA.

Results
One of the 9 infants had a deletion of the entire FOXF1 gene. In the remaining 8 infants, deletions were found in the DNA distant and upstream from FOXF1. These deletions affected an area of the DNA that is involved in the regulation of the FOXF1 gene. None of these deletions were found in their parents blood and thus represent new (de novo) genetic errors. All of the deletions arose on the chromosome that the infant inherited from its mother. They thus represent abnormalities in chromosome replication when an egg is being made in a mother’s ovary. The study additionally showed that FOXF1 is not expressed equally from maternal and paternal DNA, further confirming paternal imprinting.

Discussion
This study adds to the body of ACDMPV research to date in agreeing that mutations in or around the FOXF1 gene are passed to the affected infant through the mother, whether this be though de novo changes or familial cases of ACDMPV. It also shows that deletions upstream from the FOXF1 gene are commonly detected using CGH in infants with ACDMPV who do not have a mutation of the FOXF1 gene itself, further stressing the importance of CGH in the genetic assessment of infants with ACDMPV. This can be particularly helpful for parents interested in pre-natal diagnosis of future pregnancies. Thanks to Dr. Simon Ashwell, father to David, for this summary.

    • Case Series Of Infants With Atypical Presentations Of Alveolar Capillary Dysplasia With Misalignment Of The Pulmonary Veins (Acd/Mpv) Who Underwent Bilateral Lung Transplantation
      Towe, C., White, F., Sweet, S., Grady, R. M., Faro, A., Michelson, P., Eghtesady, P., Boston, U., Hamvas, A., Cole, F. S. & Wambach, J. (2013): In: Pediatric Transplantation Volume 17, p70 August 2013
      http://onlinelibrary.wiley.com/doi/10.1111/petr.12122/abstract
    • Paracorporeal lung assist device: An innovative surgical strategy for bridging to lung transplant in an infant with severe pulmonary hypertension caused by alveolar capillary dysplasia
      Boston US, Fehr J, Gazit AZ, Eghtesady P. In: J Thorac Cardiovasc Surg. 2013 Oct;146(4):e42-3. doi: 10.1016/j.jtcvs.2013.06.014. Epub 2013 Jul 18.
      http://www.ncbi.nlm.nih.gov/pubmed/23871141 pdficon_small *FREE – Full Article*
    • Neonatal Paracorporeal Lung Assist Device for Respiratory Failure.
      Hoganson, David M.; Gazit, Avihu Z.; Sweet, Stuart C.; Grady, R. Mark; Huddleston, Charles B.; Eghtesady, Pirooz (2013): In: Ann Thorac Surg. 2013 Feb;95(2):692-4. doi: 10.1016/j.athoracsur.2012.05.128.
      http://www.ncbi.nlm.nih.gov/pubmed/23336880 pdficon_small *FREE – Full Article*
    • Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV): A Case Series
      Joana Miranda, Gustavo Rocha, Henrique Soares, Ana Vilan, Otília Brandão and Hercília Guimarães (2013): In: Case Rep Crit Care. 2013; 2013: 327250.
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009999/ pdficon_small *FREE – Full Article*
    • Interstitial lung disease in infants: new classification system, imaging technique, clinical presentation and imaging findings.
      Lee EY (2013): In: Pediatr Radiol. 2013 Jan;43(1):3-13; quiz p.128-9. doi: 10.1007/s00247-012-2524-x. Epub 2012 Nov 15.
      http://www.ncbi.nlm.nih.gov/pubmed/23229343

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2012

    • Loss of Semaphorin-Neuropilin-1 Signaling Causes Dysmorphic Vascularization Reminiscent of Alveolar Capillary Dysplasia
      Joza, Stephen; Wang, Jinxia; Fox, Emily; Hillman, Valerie; Ackerley, Cameron; Post, Martin (2012): In: Am. J. Pathol. 181 (6), 2003–2017.
      http://www.sciencedirect.com/science/article/pii/S0002944012006797 pdficon_small *FREE – Full Article*
    • Long Survival of Congenital Alveolar Capillary Dysplasia Patient with No Inhalation and Epoprostenol: Effect of Sildenafil, Beraprost and Bosentan.
      Kodama, Yoshihiko; Tao, Katsuo; Ishida, Fumihiko; Kawakami, Tadashi; Tsuchiya, Keiji; Ishida, Kazuo et al. (2012): In: Pediatr Int 54 (6), 923–6.
      http://www.ncbi.nlm.nih.gov/pubmed/23279022
    • Outcomes of Neonates requiring Extracorporeal Membrane Oxygenation for Irreversible Pulmonary Dysplasia: The Extracorporeal Life Support Registry Experience
      Lazar, David A.; Olutoye, Oluyinka O.; Cass, Darrell L.; Fernandes, Caraciolo J.; Welty, Stephen E.; Johnson, Karen E. et al. (2012). In: Pediatr Crit Care Med 13 (2), 188–90.
      http://www.ncbi.nlm.nih.gov/pubmed/21666536
    • New coding in the International Classification of Diseases, Ninth Revision, for Children’s Interstitial Lung Disease
      Popler, Jonathan; Lesnick, Burton; Dishop, Megan K.; Deterding, Robin R. (2012):. In: Chest 142 (3), 774–80.
      http://www.ncbi.nlm.nih.gov/pubmed/22948581 pdficon_small *FREE – Full Article*
    • A Familial Case of Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins Supports Paternal Imprinting of Foxf1 in Human
      Sen, Partha; Gerychova, Romana; Janku, Petr; Jezova, Marta; Valaskova, Iveta; Navarro, Colby et al. (2012): In: Eur J Hum Genet.
      http://www.ncbi.nlm.nih.gov/pubmed/22990143 pdficon_small *FREE – Full Article*
    • Mesodermal Pten Inactivation leads to Alveolar Capillary Dysplasia-Like Phenotype
      Tiozzo, Caterina; Carraro, Gianni; Al, Alam Denise; Baptista, Sheryl; Danopoulos, Soula; Li, Aimin et al. (2012):. In: J. Clin. Invest. 122 (11), 3862–3872.
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484434/ pdficon_small *FREE – Full Article*
    • Analysis of FOXF1 and the FOX gene cluster in Patients with VACTERL Association
      Agochukwu, Nneamaka B.; Pineda-Alvarez, Daniel E.; Keaton, Amelia A.; Warren-Mora, Nicole; Raam, Manu ; Kamat, Aparna et al. (2011):. In: Eur J Med Genet 54 (3), 323–8.
      http://www.ncbi.nlm.nih.gov/pubmed/21315191 pdficon_small *FREE – Full Article*

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2011

    • Bedside Lung Mechanics Predict Survival in Hypoplastic Lung Disease
      Haleem, Abdul; Zia, Muhammad T.; Mishra, Ravi; Parton, Lance A.; Stringel, Gustavo; La, Gamma Edmund F. (2011):. In: Am J Perinatol 28 (4), 305–14.
      http://www.ncbi.nlm.nih.gov/pubmed/21117013
    • Misalignment of Lung Vessels and Alveolar Capillary Dysplasia: A Case Report with Autopsy.
      Hung, Shih-Pin; Huang, Shih-Hung; Wu, Chun-Hung; Chen, Wu-Charng; Kou, Ka-Em; Wang, Nan-Koong; Lin, Lung-Huang (2011): In: Pediatr Neonatol 52 (4), 232–6.
      http://www.ncbi.nlm.nih.gov/pubmed/21835371
    • Elastase Inhibitory Activity of Airway a1-Antitrypsin is Protected by Treatment with a Catalytic Antioxidant in a Baboon Model of Severe Bronchopulmonary Dysplasia
      Karaaslan, Cagatay; Hirakawa, Hiroshi; Yasumatsu, Ryuji; Chang, Ling-Yi L.; Pierce, Richard A.; Crapo, James D.; Cataltepe, Sule (2011) In: Pediatr. Re 70 (4), 363–367.
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166355/ pdficon_small *FREE – Full Article*
    • Severe Respiratory Distress Syndrome Unresponsive to Intensive Care Treatment–Diagnostic and Therapeutic Consideration
      Limbach, H-G; Hasenfus, A.; Bohle, R. M.; Baghai, A.; Loffler, G.; Gortner, L. et al. (2011): In: Klin Padiatr 223 (5), 283–6.
      http://www.ncbi.nlm.nih.gov/pubmed/21294065
    • Alveolar Capillary Dysplasia Associated with Duodenal Atresia: Ultrasonographic Findings of Enlarged, Highly Echogenic Lungs and Gastric Dilatation in a Third-Trimester Fetus
      Obata-Yasuoka, Mana; Hamada, Hiromi; Ohara, Rena; Nakao, Atsushi; Miyazono, Yayoi; Yoshikawa, Hiroyuki (2011): In: J Obstet Gynaecol Res 37 (7), 937–9.
      http://www.ncbi.nlm.nih.gov/pubmed/21410831
    • A Novel Association of Alveolar Capillary Dysplasia, Atypical Duodenal Atresia, and Subglottic Stenosi
      Shimizu, Takeru; Fukuda, Taeko; Inomata, Shinichi; Satsumae, Tsuyoshi; Tanaka, Makoto (2011): In: J Anesth 25 (2), 298–300.
      http://www.ncbi.nlm.nih.gov/pubmed/21194000
    • Collagen Iv Contributes to Nitric Oxide-Induced Angiogenesis of Lung Endothelial Cell
      Wang, Huafang; Su, Yunchao (2011) In: Am J Physiol Cell Physiol 300 (5), C979-88.
      http://www.ncbi.nlm.nih.gov/pubmed/21307347 pdficon_small *FREE – Full Article*
    • Nitric Oxide-Induced Collagen Iv Expression and Angiogenesis: Fak or Fiction? Focus on “Collagen Iv Contributes to Nitric Oxide-Induced Angiogenesis of Lung Endothelial Cells”
      James A. Stewart Jr.1,2, T. Aaron West1, and Pamela A. Lucche
      http://ajpcell.physiology.org/content/300/5/C968.short pdficon_small *FREE – Full Article*
    • 16Q24.1 Microdeletion in a Premature Newborn: Usefulness of Array-Based Comparative Genomic Hybridization in Persistent Pulmonary Hypertension of the Newborn
      Zufferey, Flore; Martinet, Danielle; Osterheld, Maria-Chiara; Niel-Butschi, Florence; Giannoni, Eric; Schmutz, Nathalie Besuchet et al. (2011):. In: Pediatr Crit Care Med 12 (6), e427-32.
      http://www.ncbi.nlm.nih.gov/pubmed/21572369 pdficon_small *FREE – Full Article*

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2010

    • Omphalocele and alveolar capillary dysplasia: a new association
      Gerrits LC, De Mol AC, Bulten J, Van der Staak FH, Van Heijst AF.
      Pediatr Crit Care Med. 2010 May;11(3):e36-7. doi: 10.1097/PCC.0b013e3181b80a75
      https://www.ncbi.nlm.nih.gov/pubmed/20453609
    • Expression of Angiogenic and Vasculogenic Proteins in the Lung in Alveolar Capillary Dysplasia/Misalignment of Pulmonary Veins: an Immunohistochemical Study
      Sen P, Choudhury T, Smith EO, Langston C.
      Pediatr Dev Pathol. 2010 Sep-Oct;13(5):354-61. Epub 2010 Mar 23
      http://www.ncbi.nlm.nih.gov/pubmed/20331367

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2009

    • Genomic and genic deletions of the FOX gene cluster on 16q24.1 and inactivating mutations of FOXF1 cause alveolar capillary dysplasia and other malformations.
      Stankiewicz P, Sen P, Bhatt SS, Storer M, Xia Z, Bejjani BA, Ou Z, Wiszniewska J, Driscoll DJ, Maisenbacher MK, Bolivar J, Bauer M, Zackai EH, McDonald-McGinn D, Nowaczyk MM, Murray M, Hustead V, Mascotti K, Schultz R, Hallam L, McRae D, Nicholson AG, Newbury R, Durham-O’Donnell J, Knight G, Kini U, Shaikh TH, Martin V, Tyreman M, Simonic I, Willatt L, Paterson J, Mehta S, Rajan D, Fitzgerald T, Gribble S, Prigmore E, Patel A, Shaffer LG, Carter NP, Cheung SW, Langston C, Shaw-Smith C.
      Am J Hum Genet. 2009 Jun;84(6):780-91. doi: 10.1016/j.ajhg.2009.05.005. Epub 2009 Jun 4.
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694971/ pdficon_small *FREE – Full Article*

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2008

    • ABCA3 mutation and pulmonary hypertension: a link with alveolar capillary dysplasia?
      Danhaive O, Peca D, Boldrini R. (2008): In: J Pediatr. 2008 Jun;152(6):891-2. doi: 10.1016/j.jpeds.2008.01.019.
      https://www.ncbi.nlm.nih.gov/pubmed/18492541

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2007

    • Diffuse Lung Disease in Young Children Application of a Novel Classification Scheme
      Children’s Interstitial Lung Disease (ChILD)Research Co-operative
      Am J Respir Crit Care Med Vol 176. pp 1120-1128, 2007
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176101/ pdficon_small *FREE – Full Article*
    • Mutations in STRA6 Cause a Broad Spectrum of Malformations Including Anophthalmia, Congenital Heart Defects, Diaphragmatic Hernia, Alveolar Capillary Dysplasia, Lung Hypoplasia, and Mental Retardation
      Francesca Pasutto, Heinrich Sticht, Gerhard Hammersen, Gabriele Gillessen-Kaesbach, David R. FitzPatrick, Gudrun Nu¨rnberg, Frank Brasch, Heidemarie Schirmer-Zimmermann, John L. Tolmie, David Chitayat, Gunnar Houge, Lorena Ferna´ndez-Marti´nez, Sarah Keating, Geert Mortier, Raoul C. M. Hennekam, Axel von der Wense, Anne Slavotinek, Peter Meinecke, Pierre Bitoun, Christian Becker, Peter Nu¨rnberg, Andre´ Reis, and Anita Rauch
      American Journal of Human Genetics Volume 80 March 2007
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1821097/ pdficon_small *FREE – Full Article*

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2006

    • Congenital Alveolar Capillary Dysplasia and associated gastrointestinal anomalies
      B. Antao, M. Samuel, E. Kiely, L. Spitz, M. Malone
      Fetal and Pediatric Pathology, Volume 25, Issue 3 July 2006 , pages 137 – 145
      http://www.ncbi.nlm.nih.gov/pubmed/17060189
    • Alveolar capillary dysplasia presenting as pneumothorax: a case report and review of literature
      Pankaj G. Roy, Prerna Patel, Anitha Vayalakkad, Colene Bowker and Kokila Lakhoo
      Pediatric Surgery International Published online: 30 March 2007
      http://www.springerlink.com/content/r87q2674vu411072/

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2005

    • Misalignment of pulmonary vessels with alveolar capillary dysplasia: association with atrioventricular septal defect and quadricuspid pulmonary valve.
      Roth W, Bucsenez D, Blaker H, Berger I, Schnabel PA.
      Virchows Arch. 2005 Dec 6;:1-4
      http://www.ncbi.nlm.nih.gov/pubmed/16331469
    • Alveolar capillary dysplasia with congenital misalignment of pulmonary vessels.
      Sihoe AD, Lee AT, To KF, Thung KH, Lee TW, Yim AP.
      Asian Cardiovasc Thorac Ann. 2005 Mar;13(1):82-4.
      http://www.ncbi.nlm.nih.gov/pubmed/15793061
    • Persistent pulmonary hypertension of newborn due to congenital capillary alveolar dysplasia.
      Singh SA, Ibrahim T, Clark DJ, Taylor RS, George DH.
      Pediatr Pulmonol. 2005 Oct;40(4):349-53.
      http://www.ncbi.nlm.nih.gov/pubmed/15957181

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2004

    • Prolonged survival in alveolar capillary dysplasia syndrome
      Christoph Licht , Sabine Schickendantz, Narayanswami Sreeram, Georg Arnold, Rainer Rossi, Anne Vierzig, Udo Mennicken and Bernhard Roth
      European Journal of Pediatrics Volume 163, Number 3 / March, 2004
      http://www.springerlink.com/content/lw4aqepmkk235b4m/
    • A novel association of alveolar capillary dysplasia and duodenal atresia with paradoxical dilatation of the duodenum
      Noriaki Usuia, Masafumi Kamiyamaa, Shinkichi Kamataa, Akihiro Yonedaa, Yuko Tazukea, Masahiro Fukuzawaa
      Journal of Ped Surgery Volume 39, Issue 12, Pages 1808-1811
      http://www.jpedsurg.org/article/PIIS0022346804005718/abstract
    • Defective Lung Vascular Development and Fatal Respiratory Distress in Endothelial NO Synthase – Deficient Mice; A Model of Alveolar Capillary Dysplasia
      Han R, Babaei S, Robb M, Lee T, Ridsdale R, Ackerley C, Post M, Stewart D
      Circulation Research 2004;94:1115.
      http://circres.ahajournals.org/cgi/content/full/94/8/1115 pdficon_small *FREE – Full Article*

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2002

    • Alveolar Capillary Dysplasia: a cause of Persistent Pulmonary Hypertension of the Newborn
      Alameh J, Bachiri A, Devisme L, Truffert P, Rakza T, Riou Y, Manouvrier S,Lequien P, Storme L
      European Journal of Pediatrics, 161 262-266
      http://www.ncbi.nlm.nih.gov/pubmed/12012221
    • Incidence of Alveolar Capillary Dysplasia in severe idiopathic Persistent Pulmonary Hypertension of the Newborn
      Tibballs J, Chow CW
      Journal of Paediatrics and Childrens Health, 38 397-400
      http://www.ncbi.nlm.nih.gov/pubmed/12174004

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2001

    • Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins and Anterior Segment Dysgenesis of the Eye: A Report of a New Association and Review of the Literature
      Merchak A, Lueder G, White F, Cole F, Sessions F
      Journal of Perinatology, 21 327-330
    • Alveolar capillary dysplasia with antenatal anomalies mimickin trisomy 21
      McGaughran J, Souter DJ, Kuschel CA
      Journal of Paediatrics and Children’s Health (Australia), 37 85-86
    • Congenital Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins Associated with Hypoplastic Left Heart Syndrome
      Rabah R, Poulik JM
      Pediatric and Developmental Pathology, 4 167-174

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2000

    • Clinical approach to inhaled nitric oxide therapy in the newborn with hypoxemia
      John P. Kinsella, MD, Steven H. Abman
      Journal of Pediatrics June 2000, Volume 136, Number 6, p717 to p726
    • Urethral atresia in a neonate with alveolar capillary dysplasia and pulmonary venous misalignment
      Vick, Ralph N: Owens, Thomas: Moise, Kenneth J: Chescheir, Nancy: Bukowski, Timothy P.
      Urology (Online) 2000 May 1;55(5):774.
      Division of Urology, University of North Carolina Hospitals, Chapel Hill, North Carolina, USA.
    • Congenital misalignment of pulmonary vessels and Alveolar Capillary Dysplasia: how to manage a neonatal irreversable lung disease?
      Somaschini M, Bellan C, Chinaglia D, Riva S, Colombo
      Journal of Perinatology, April-May 2000 20(3) 189-192
    • Alveolar Capillary Dysplasia. Report of a cause of prolonged life without extracorporeal membrane oxygenation (ECMO) and a review of literature
      Al-Hathlol K, Phillips S, Seshia MK, Casiro O, Alvaro RE, Rigatto H
      Early Human Developpment, 2000 57 85-94
    • Congenital misalignment of pulmonary veins with Alveolar Capillary Dysplasia causing persistent neonatal pulmonary hypertension: report of two affected siblings
      Guiterrez C, Rodriguez A, Palenzuela S, Forteza C, Rossello JLD
      Paediatric and Developmental Pathology, 2000 3 271-276

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1999

    • An alternatively spliced surfactant protein B mRNA in normal human lung:disease implication
      LIN Zhenwu, WANG Guirong, DEMELLO Daphne E. and FLOROS Joanna
      Biochem. J. (1999) 343, 145-149
      http://www.biochemj.org/bj/343/0145/3430145.pdf pdficon_small *FREE – Full Article*
    • Alveolar Capillary Dysplasia: an emerging syndrome
      Thibeault DW, Garola RE, Killbride Howard W
      Journal of Paediatrics, May 1999 134(5) 661-662
    • Prospective diagnosis of Alveolar Capillary Dysplasia in infants with congenital heart disease
      Lane JR, Siwik E, Preminger T, Stork E, Spector M
      The American Journal of Cardiology, September 1999 84 618-620
    • Alveolar Capillary Dysplasia: diagnostic potential for cardiac catheterisation
      Hintz SR, Vincent JA, Pitlick PT, Fineman JR, Steinhiorn RH, Kim GE, Benitz WE
      Journal of Perinatology, 1999 19(6) 441-446

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1998

    • Case 3-Clinical Summary Pulmonary Hypertension in a Newborn
      Warnock, ML
      mw6825@itsa.uscf.edu
    • Neonatal hypoxemia due to misaligned pulmonary vessels with Alveolar Capillary Dysplasia
      Liet JM, Joubert M, Gournay V, Godon N, Godde F, Nomballais MF, Roze JC
      Arch Paediatrics, January 1998 5(1) 27-30
    • Familial Persistent Pulmonary Hypertension of the Newborn resulting from Misalignment of the Pulmonary Vessels (Congenital Alveolar Capillary Dysplasia)
      Vassal HB, Malone M, Petros AJ, Winter RM
      Journal of Medical Genetics, January 1998
    • Alveolar Capillary Dysplasia with and without misalignment of pulmonary veins: an association of congenital abnormalities
      Garola RE, Thibeault DW
      American Journal of Perinatology, February 1998 15(2) 103-107
    • Inhaled nitric oxide for the early treatment of persistent pulmonary hypertension of the newborn: a randomised, double masked placebo controlled, dose response, multi centre study
      Davidson D, Barefield ES, Kattwinkel J, Ducell G et al
      Paediatrics, March 1998
    • Morphologic analysis of the pulmonary vascular bed in infants exposed in utero to prostaglandin synthetase inhibitors
      Levin DL, Fixler DE, Morris FC, Tyson J
      The Journal of Paediatrics, March 1998 92(3) 478-483
    • Test and Teach Number 88: Explanation and Diagnosis: Alveolar Capillary Dysplasia
      Cluroe AD
      Pathology, May 1998 30(155) 205-206
    • Urethral atresia in a neonate with Alveolar Capillary Dysplasia and pulmonary venous misalignment
      Vick RN, Owens T, Moise KJ, Chescheir N, Bukiwski TP
      Urology, 1 May 1998 55(5) 774
    • Clinical pathologic conference: a newborn infant with pulmonary hypertension
      Montgomery V, Buchino JJ
      The Journal of Paediatrics, July 1998
    • Alveolar Capillary Dysplasia with misalignment of pulmonary veins: a rare but fatal cause of neonatal respiratory failure
      Kane td, Greenburg JM, Bove KE, Warner BW
      Paediatric Surgery International, November 1998 14(1-2) 89-91
    • Alveolar Capillary Dysplasia with and without misalignment of the veins
      Thibeault DW, Garola R
      American Journal of Perinatology, 1998 41 270A
    • Pulmonary Hypertension due to Alveolar Capillary Dysplasia with misalignment of lung vessels presenting during second week of life
      Arora DS, Sarvananthan R, Ahmed Z, Brownlee KG, Cullinane C
      Pediatric and Developmental Pathology, 1998 457

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1997

    • Pulmonary Pathology of Patients with Partial Liquid Ventilation
      Bruch LA, Flint A, Hirschl.
      Mod Pathol. 1997 May;10(5):463-8
      University of Michigan Medical Center, USA
    • Early fetal development of lung vasculature
      DE deMello, D Sawyer, N Galvin and LM Reid
      American Journal of Respiratory Cell and Molecular Biology 16(5); 568
    • Nitric oxide inhalation therapy for an infant with persistent pulmonary hypertension caused by misalignment of pulmonary veins with Alveolar Capillary Dysplasia
      Kitayama Y, Kamata, Okuyama, Usui, Sawai, Kobayashi, Fukui, Okada
      Journal of Paediatric Surgery, January 1997 32 99-100
    • Combined therapy with inhaled Nitric Oxide and intravenous Prostacyclin in an infant with Alveolar Capillary Dysplasia
      Parker TA, Ivy DD, Kinsella JP, Torielli F, Ruyle SZ, Thilo EH, Abman SH
      American Journal of Respiratory and Critical Care Medicine, February 1997 155 743-746
    • Inhaled Nitric Oxide enhances oxygenation but not survival in infants with Alveolar Capillary Dysplasia
      Steinhorn RH, Cox, Fineman, Finer, Rosenburg, Silver, Tyebkhan, Zwass, Morin
      Journal of Paediatrics, March 1997 417-422
    • Obscure, or at least unusual paediatric lung diseases: Alveolar Capillary Dysplasia with misaligned pulmonary veins
      Askin FB
      Outline for presentation for Society of Paediatric Pathology, May 1997
    • Pathological case of the month: diagnosis and discussion. Congenital Alveolar Capillary Dysplasia and misalignment of the pulmonary vessels
      Rehan V, Philips S, Fajardo C, Seshia MM
      Archives of paediatric and Adolescent Medicine, November 1997 151 1163-1164
    • So called congenital alveolar dysplasia. Description of case
      Aragona F et al
      Arch De Vecchi Anat Patol, December 1997 62(2-3) 331-347
    • ItalianInhaled Nitric Oxide and persistent pulmonary hypertension of the newborn
      Roberts JD, Fineman JR, Morin FC, Shaul PW, Rimar S, Schreiber MD, Polin RA, Zwass MS, Zayek MM, Gross I, Heymann MA, Zapol WM, Thusu KG, Zellers TM, Wylam ME, Zalavsky
      New England Journal of Medicine, 1997 336 605-610
    • Alveolar Capillary Dysplasia: lung biopsy diagnosis, Nitric Oxide responsiveness and bronchial generation count
      Sirkin W, O’Hare BP, Cox PN, Perrin D, Cutz E, Silver MM
      Paediatric Pathology and Laboratory Medicine, 1997 17 125-132
    • Improved oxygenation in a randomised trial of inhaled Nitric Oxide for persistent pulmonary hypertension of the newborn
      Wessel DL, Adatia I, Van Marter LJ, Thompson JE, Kane JW, Stark AR, Kourembanas S
      Paediatrics, 1997 100(5) E7
    • Congenital Alveolar Dysplasia : a rare cause of persistent pulmonary hypertension
      Haradia S, Lochbuhler H, Heger A, Nerlich A, Diebold J, Wiest I, Muller-Hocker J, Lohrs U
      Paediatric Pathology and Laboratory Medicine, 1997 17 959-975

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1996

    • 1996Manouvrier-Hanu, Devisme, Farre, Hue, Storme, Kacet, Boute-Benejean, Farriaux
      Genetic Counselling, November 1996 7(4) 249-255
    • The role of Nitric Oxide in the treatment of neonatal pulmonary hypertension.
      Mariani G, Barefield ES, Carlo WA
      Curr Opin Pediatr Apr, 8(2) 118-125

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1995

    • Congenital Alveolar Capillary Dysplasia: a developmental vascular anomaly causing persistent pulmonary hypertension of the newborn
      Khorsand J, Tennant R, Gillies C, Phillips AF
      Paediatric Pathology, January 1995 3(2-4) 299-306
    • Repair of congenital diaphragmatic hernia after weaning from extracorporeal membrane oxygenation
      Adolph V, Flageole H, Perreault T, Johnson A, Nguyen L, Youssef S, Guttman F, Laberge JM
      Journal of Peadiatric Surgery, February 1995 30(2) 349-352
    • Pulmonary malformations associated with congenital cardiopathy
      De Rosa N, Aliperta M
      Pathologica, February 1995 87(1) 14-19
    • ItalianRecent developments in the pathophysiology and treatment of persistent pulmonary hypertension
      Kinsella JP, Abman SH
      Journal of Paediatrics, June 1995 126(6) 853-864
    • Misalignment of lung vessels and Alveolar Capillary Dysplasia
      Oldenburg J, Van Der Pal HJ, Schrevel LS, Blok AP, Wagenvoort CA
      Histpathology, August 1995 27(2) 192-194
    • Timing of repair of congenital diaphramatic hernia requiring extracorporeal membrane oxygenation support
      Sigalet DL, Tierney A, Adolph V, Perreault T, Finer N, Hallgren R, Laberge JM
      Journal of Paediatric Surgery, August 1995 30(8) 1183-1187
    • Alveolar Capillary Dysplasia – A cause of persistent pulmonary hypertension unresponsive to a second course of extracorporeal membrane oxygenation
      Chelliah BP, Brown D, Cohen M, Talleyrand AJ, Shen-Schwarz S
      Paediatrics, December 1995 96(6) 1159-1161
    • Congenital misalignment of pulmonary vesels: an unusual syndrome associated with PPHN
      Ng PC, Lewindon, Sui, To, Wong
      Acta Paediatrics, 1995 84 349-53

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1994

    • Misalignment of the pulmonary veins with Alveolar Capillary Dysplasia: affected siblings and variable phenotypic expression
      Boggs S, Harris MC, Hoffman DJ, Goel R, McDonald-McGinn D, Langston C, Zackai E, Ruchelli E
      Journal of Paediatrics, January 1994 124(1) 125-128

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1993

    • Late presentation of misalignment of lung vessels with Alveolar Capillary Dysplasia
      Adbllah HI, Karmazin N, Marks LA
      Critical Care Medicine, April 1993 21(4) 628-630
    • Familial persistent pulmonary hypertension in two siblings with phocomelia and Alveolar Capillary Dysplasia (ACD) – a new syndrome?
      Simonton SC, Chrenka BA
      Modern Pathology, 1993 6 9

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1992

    • Misalignment of Lung Vessels and Alveolar Capillary Dysplasia
      Drut, Ricardo
      Patologia, 1992; 30,135-137
      Hospital de Ninos, La Plata, Republica Argentina
    • Persistent pulmonary hypertension of the newborn due to Alveolar Capillary Dysplasia
      Culliane C, Cox P, Silver MM
      Paediatric Pathology, July/august 1992 12(4) 499-514
    • Effects of Dexamethasone therapy on fibronectin and albumin levels in lung secretions of infants with bronchopulmonary dysplasia
      Watts CL, Bruce MC
      Journal of Paediatrics, October 1992 121(4) 597-607
    • An unusual cause of respiratory distress in the newborn
      Wise HA et al
      Journal of Urology, November 1992 108(5) 792-793
    • Misalignment of pulmonary veins with Alveolar Capillary Dysplasia as a cause of persistent neonatal pulmonary hypertension
      Butler MW, Ursell PC, Wung JET, Stolar CJH
      Neonatal Pulmonology, 1992 #1802
    • Natural surfactant for neonatal respiratory distress syndrome in very early premature infants: a 1992 update
      Gortner L
      Journal of Perinatol Medicine, 1992 20(6) 409-419
    • Familial persistent pulmonary hypertension of the newborn: a new autosomal recessive disease with unique histologic findings
      McDonald-McGinn DM, Ruchelli E, Uri A, Langston C, Bowen F, Harris MC, Polin R, Karmazin N, Goel R, Boggs S, Hoffman D, Zackai E
      American Journal of Human Genetics, 1992 51(Supplement) A102

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1991

    • Misalignment of the pulmonary veins with Alveolar Capillary Dysplasia
      Langston C
      Paediatric Pathology, 1991 11 163-170

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1990

    • Neonatal hyperoxia alters the pulmonary alveolar and capillary structure of 40 day old rats
      Randall SH, Mercer RR, Young SL
      American Journal of Pathology, June 1990 136(6) 1259-1266
    • Primary Alveolar Capillary Dysplasia
      Newman B, Yunis E
      Paediatric Radiology, 1990 21(1) 20-22

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1989

    • Misalignment of the lung vessels and Alveolar Capillary Dysplasia: a cause of persistent pulmonary hypertension
      Cater G, Thibeault DW, Beatty EC, Kilbride HW, Huntrakoon M
      Journal of Paediatrics, February 1989 114 293-300

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1986

    • Misalignment of lung vessels: a syndrome causing persistent neonatal pulmonary hypertension
      Wagenvoort CA
      Human Pathology, July 1986 17(7) 727-730

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1984

    • The structural basis of PPHN
      Geggel RL, Reid LM
      Clinical Perinatology, October 1984 11(3) 525-549
    • Familial persistent pulmonary hypertension
      Shohet I, Reichman B, Schibi G, Brish M
      Archives of Disease in Childhood, 1984 59 783-785

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1982

    • The radial alveolar count method of Emery and Mithal: a reappraisal 2- Intrauterine and early postnatal lung growth
      Cooney TP, Thurlbeck WM
      Thorax, 1982 37 580-583

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1981

    • Congenital Alveolar Capillary Dysplasia – an unusual cause of respiratory distress in the newborn
      Janney CG, Askin FB, Kuhn C
      American Journal of Clinical Pathology, November 1981

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1978

    • Fetal hypertension and the development of increased pulmonary vascular smooth muscle: A possible mechanism for persistent pulmonary hypertension of the newborn infant
      Daniel L. Levin, et. al
      The Journal of Pediatrics 1978;92:2:265-269
      Department of Pediatrics, The University of Texas Health Science Center at Dallas, Dallas, TX
    • Morphologic analysis of the pulmonary vascular bed in infants exposed in utero to prostaglandin synthetase inhibitors.
      Levin DL, Fixler DE, Morriss FC, Tyson J.
      The Journal of Pediatrics. March 98, 92 (3); 478-483.
      Dallas, Texas, USA
    • A simple technique for measuring alveolar CO2 in infants
      Dumpit FEM, Brady JP
      Journal of Applied Physiology, October 1978 45 648-650

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1976

    • Persistent fetal circulation: newly recognised structural features
      Haworth SG, Reid L
      Journal of Paediatrics, April 1976 88 614-620
    • Congenital Alveolar Capillary Dysplasia of the lung: critical review and personal cases
      De Turris P et al
      Patholigica, May 1976 68(979-980) 211-221Italian

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1975

    • Proceedings: Congenital Alveolar Lung Dysplasia
      Munterfering H, et al.
      Verh Dtsch Ges Pathol. 1975 Jan 1; 59: 576

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1973

    • Unilateral congenital dysplasia of lung associated with vascular abnormalities
      Hislop A, Sanderson M, Reid L
      Thorax, 1973 28 435-441

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1972

    • An Unusual Cause of Respiratory Distress in a Newborn
      Wise, HA 2nd, et al.
      J Urol. Nov,1972; 108 (5): 792-793.
      Ohio State University Hospital

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1971

    • The Effects of Maternal Hypoxia and Hyperoxia Upon the Neonatal Pulmonary Vasculature
      Stanley J. Goldberg, et al.
      Pediatrics 1971;48:528-533
      University of Arizona, College of Medicine, Department of Pediatrics, Tucson, Arizona

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1966

    • Congenital Alveolar Capillary Dysplasia of the lung in newborn infant
      Habanec B
      Cesk Pediatr, March 1966 21(3) 256-258 Czech

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1965

    • Interstitial lung disease (alveolar-capillary block)
      Read J
      New Zealand Medical Journal, December 1965 64(400 Supplement) 96

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1948

    • Congenital Alveolar Dysplasia of the lungs
      MacMahon HE
      American Journal of Pathology, 1948 24 919-930

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