Autopsy and Case Reports
Autopsy and Case Reports
Article / Autopsy Case Report

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

Gabriel Nuncio Benevides; Patricia Picciarelli de Lima; Aloisio Felipe-Silva; Silvana Maria Lovisolo; Ana Maria Andrello Gonçalves Pereira de Melo

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


Alveolar capillary dysplasia, Respiratory Insufficiency, Hypertension, Pulmonary, Newborn, Siblings, Autopsy


Bishop NB, Stankiewicz P, Steinhorn RH. Alveolar capillary dysplasia. Am J Respir Crit Care Med. 2011;184(2):172-9. []. [PMID:21471096]

Sen P, Yang Y, Navarro C, Silva I, Szafranski P, Kolodziejska KE, et al. Novel FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins imply a role for its DNA binding domain. Hum Mutat. 2013;34(6):801-11. []. [PMID:23505205]

Tibballs J, Chow CW. Incidence of alveolar capillary dysplasia in severe idiopathic persistent pulmonary hypertension of the newborn. J Paediatr Child Health. 2002;38(4):397-400. []. [PMID:12174004]

Hoganson DM, Gazit AZ, Boston US, Sweet SC, Grady RM, Huddleston CB, et al. Paracorporeal lung assist devices as a bridge to recovery or lung transplantation in neonates and young children. J Thorac Cardiovasc Surg. 2014;147(1):420-6. []. [PMID:24199759]

MacMahon HE. Congenital alveolar dysplasia; a developmental anomaly involving pulmonary alveoli. Pediatrics. 1948;2(1):43-57. [PMID:18874463].

Nguyen L, Riley MM, Sen P, Galambos C. Alveolar capillary dysplasia with misalignment of pulmonary veins with a wide spectrum of extrapulmonary manifestations. Pathol Int. 2013;63(10):519-21. []. [PMID:24147432]

Dishop MK. Paediatric interstitial lung disease: classification and definitions. Pathol Int. 2013;63(10):519-21. [PMID:24147432].

Deutsch GH, Young LR, Deterding RR, Fan LL, Dell SD, Bean JA, et al. Diffuse lung disease in young children: application of a novel classification scheme. Am J Respir Crit Care Med. 2007;176(11):1120-8. []. [PMID:17885266]

Cassidy J, Smith J, Goldman A, Haynes S, Smith E, Wright C, et al. The incidence and characteristics of neonatal irreversible lung dysplasia. J Pediatr. 2002;141(3):426-8. []. [PMID:12219067]

Stankiewicz P, Sen P, Bhatt SS, Storer M, Xia Z, Bejjani BA, et al. Genomic and genic deletions of the FOX gene cluster on 16q24.1 and inactivating mutations of FOXF1 cause alveolar capillary dysplasia and other malformations. Am J Hum Genet. 2009;84(6):780-91. []. [PMID:19500772]

Miranda J, Rocha G, Soares H, Vilan A, Brandão O, Guimarães H. Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV): A Case Series. Case Rep Crit Care. 2013;2013:327250. [PMID:24829819].

Citti A, Peca D, Petrini S, Cutrera R, Biban P, Haass C, et al. Ultrastructural characterization of genetic diffuse lung diseases in infants and children: a cohort study and review. Ultrastruct Pathol. 2013;37(5):356-65. []. [PMID:24047351]

Nogee LM. Genetic basis of children’s interstitial lung disease. Pediatr Allergy Immunol Pulmonol. 2010;23(1):15-24. []. [PMID:22087432]

Sen P, Gerychova R, Janku P, Jezova M, Valaskova I, Navarro C, et al. A familial case of alveolar capillary dysplasia with misalignment of pulmonary veins supports paternal imprinting of FOXF1 in human. Eur J Hum Genet. 2013;21(4):474-7. []. [PMID:22990143]

Alameh J, Bachiri A, Devisme L, Truffert P, Rakza T, Riou Y, et al. Alveolar capillary dysplasia: a cause of persistent pulmonary hypertension of the newborn. Eur J Pediatr. 2002;161(5):262-6. []. [PMID:12012221]

Licht C, Schickendantz S, Sreeram N, Arnold G, Rossi R, Vierzig A, et al. Prolonged survival in alveolar capillary dysplasia syndrome. Eur J Pediatr. 2004;163(3):181-2. []. [PMID:14677063]

Garola RE, Thibeault DW. Alveolar capillary dysplasia, with and without misalignment of pulmonary veins: an association of congenital anomalies. Am J Perinatol. 1998;15(2):103-7. []. [PMID:9514134]

Don M, Orsaria M, Da Dalt E, Tringali C, Sacher B. Rapidly fatal “congenital lung dysplasia”: a case report and review of the literature. Fetal Pediatr Pathol. 2014;33(2):109-13. []. [PMID:24467188]

Langenstroer M, Carlan SJ, Fanaian N, Attia S. Congenital acinar dysplasia: report of a case and review of literature. AJP Rep. 2013;3(1):9-12. []. [PMID:23943701]

Sen P, Thakur N, Stockton DW, Langston C, Bejjani BA. Expanding the phenotype of alveolar capillary dysplasia (ACD). J Pediatr. 2004;145(5):646-51. []. [PMID:15520767]

Gamillscheg A, Zobel G, Spuller E, Reiterer F, Beitzke A. Aortic coarctation associated with alveolar capillary dysplasia and misalignment of the pulmonary veins. Pediatr Cardiol. 2008;29(1):191-4. []. [PMID:17874220]

Hung SP, Huang SH, Wu CH, Chen WC, Kou KE, Wang NK, et al. Misalignment of lung vessels and alveolar capillary dysplasia: a case report with autopsy. Pediatr Neonatol. 2011;52(4):232-6. []. [PMID:21835371]

Roy PG, Patel P, Vayalakkad A, Bowker C, Lakhoo K. Alveolar capillary dysplasia presenting as pneumothorax: a case report and review of literature. Pediatr Surg Int. 2007;23(9):915-7. []. [PMID:17394004]

Shimizu T, Fukuda T, Inomata S, Satsumae T, Tanaka M. A novel association of alveolar capillary dysplasia, atypical duodenal atresia, and subglottic stenosis. J Anesth. 2011;25(2):298-300. []. [PMID:21194000]

Sihoe AD, Lee AT, To KF, Thung KH, Lee TW, Yim AP. Alveolar capillary dysplasia with congenital misalignment of pulmonary vessels. Asian Cardiovasc Thorac Ann. 2005;13(1):82-4. []. [PMID:15793061]

Taborosi B, Tödt-Pingel I, Kayser G, Dittrich S. A rare case of aortic coarctation and ventricular septal defect combined with alveolar capillary dysplasia. Pediatr Cardiol. 2007;28(4):319-23. []. [PMID:17530317]

Antao B, Samuel M, Kiely E, Spitz L, Malone M. Congenital alveolar capillary dysplasia and associated gastrointestinal anomalies. Fetal Pediatr Pathol. 2006;25(3):137-45. []. [PMID:17060189]

Michalsky MP, Arca MJ, Groenman F, Hammond S, Tibboel D, Caniano DA. Alveolar capillary dysplasia: a logical approach to a fatal disease. J Pediatr Surg. 2005;40(7):1100-5. []. [PMID:16034752]

Kodama Y, Tao K, Ishida F, Kawakami T, Tsuchiya K, Ishida K, et al. Long survival of congenital alveolar capillary dysplasia patient with NO inhalation and epoprostenol: effect of sildenafil, beraprost and bosentan. Pediatr Int. 2012;54(6):923-6. []. [PMID:23279022]

Usui N, Kamiyama M, Kamata S, Yoneda A, Tazuke Y, Fukuzawa M. A novel association of alveolar capillary dysplasia and duodenal atresia with paradoxical dilatation of the duodenum. J Pediatr Surg. 2004;39(12):1808-11. []. [PMID:15616937]

Vassal HB, Malone M, Petros AJ, Winter RM. Familial persistent pulmonary hypertension of the newborn resulting from misalignment of the pulmonary vessels (congenital alveolar capillary dysplasia). J Med Genet. 1998;35(1):58-60. []. [PMID:9475097]

Morin FC 3rd, Stenmark KR. Persistent pulmonary hypertension of the newborn. Am J Respir Crit Care Med. 1995;151(6):2010-32. []. [PMID:7767553]

Ahmed S, Ackerman V, Faught P, Langston C. Profound hypoxemia and pulmonary hypertension in a 7-month-old infant: late presentation of alveolar capillary dysplasia. Pediatr Crit Care Med. 2008;9(6):e43-6. []. [PMID:18997591]

Singh SA, Ibrahim T, Clark DJ, Taylor RS, George DH. Persistent pulmonary hypertension of newborn due to congenital capillary alveolar dysplasia. Pediatr Pulmonol. 2005;40(4):349-53. []. [PMID:15957181]

Hugosson CO, Salama HM, Al-Dayel F, Khoumais N, Kattan AH. Primary alveolar capillary dysplasia (acinar dysplasia) and surfactant protein B deficiency: a clinical, radiological and pathological study. Pediatr Radiol. 2005;35(3):311-6. []. [PMID:15490144]

Janney CG, Askin FB, Kuhn C 3rd. Congenital alveolar capillary dysplasia: an unusual cause of respiratory distress in the newborn. Am J Clin Pathol. 1981;76(5):722-7. [PMID:7293984]

Plat G, Rouquette I, Marcoux MO, Bloom MC, Acar P, Dulac Y. [Alveolar capillary dysplasia and persistent pulmonary hypertension of the newborn]. Arch Mal Coeur Vaiss. 2007;100(5):458-61. [PMID:17646774]

Shankar V, Haque A, Johnson J, Pietsch J. Late presentation of alveolar capillary dysplasia in an infant. Pediatr Crit Care Med. 2006;7(2):177-9. []. [PMID:16474258]

Eulmesekian P, Cutz E, Parvez B, Bohn D, Adatia I. Alveolar capillary dysplasia: a six-year single center experience. J Perinat Med. 2005;33(4):347-52. []. [PMID:16207122]

Deshmukh H, Lioy J. The use of early lung biopsy in detection of fatal pulmonary disease in the neonate. J Pediatr. 2014;164(4):934-6. []. [PMID:24373577]

Lazar DA, Olutoye OO, Cass DL, Fernandes CJ, Welty SE, Johnson KE, et al. Outcomes of neonates requiring extracorporeal membrane oxygenation for irreversible pulmonary dysplasia: the Extracorporeal Life Support Registry experience. Pediatr Crit Care Med. 2012;13(2):188-90. []. [PMID:21666536]


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