Pediatric Pulmonology
Case Report
Unilateral Pulmonary Agenesis: A Report of Four Cases, Two Diagnosed Antenatally and Literature Review S. Kayemba-Kay’s, MBBS, MD,1* V. Couvrat-Carcauzon, MD,2 V. Goua, MD,3 G. Podevin, PhD,4 M. Marteau, MD,5 E. Sapin, PhD,6 and G. Levard, PhD2 Summary. Pulmonary agenesis is a rare congenital malformation of lung development defined as complete absence of lung tissues, bronchi, and pulmonary vessels; it may be uni- or bilateral. The right-sided form carries the poorest prognosis due to severity of co-existent anomalies. Its diagnostic circumstances are variables: first reported cases were diagnosed at autopsy, but early postnatal as well as fortuitous discovery have been reported. In recent years, progress in obstetrical imaging has made antenatal diagnosis possible so that fetal ultrasound and MRI allow early diagnosis and refinement by permitting the elimination of differential diagnoses (diaphragmatic hernia, cystic adenomatoid malformation of the lung, giant lobar emphysema, and situs inversus). This anomaly is compatible with normal life provided co-existent malformations are thoroughly investigated and managed in a multidisciplinary setting. We report four cases of lung agenesis two of which were diagnosed antenatally at 23rd and 30th weeks of gestation respectively. Our aim is to describe the circumstances having led to diagnosis and report both follow-up and outcome of our patients. Pediatr Pulmonol. ß 2013 Wiley Periodicals, Inc. Key words: pulmonary agenesis; antenatal diagnosis; prognosis; co-existent anomalies; fetal MRI. Funding source: none reported
Pulmonary agenesis is a rare congenital malformation of lung development that was first described by De Pozze in 1673 from a necropsy of an adult female. Defined as complete absence of lung tissues, bronchi, and pulmonary
vessels,1 it may be unilateral or bilateral, partial, or complete. With about 300 cases reported in the literature, this malformation has an estimated frequency between 1/10,000 to 1/15,000 autopsies, its occurrence is usually sporadic in most of cases, but parental consanguinity has been reported by Mardini and Nyhan.2
1 Neonatal Medicine Section, Service de Pediatrie & Medecine Neonatale, Victor Jousselin Hospital, Dreux, France.
6 Pediatric Surgery Department, Dijon University Teaching Hospital, Dijon, France.
2
Conflict of interest: None.
INTRODUCTION
Pediatric Surgery Section, Departement Medico-Chirurgical de Pediatrie, Poitiers University Teaching Hospital, Poitiers, France.
3
Antenatal Diagnosis Section, Obstetrics & Gynecology Department, Poitiers University Teaching Hospital, Poitiers, France.
Correspondence to: S. Kayemba-Kay’s, Unite de Neonatologie, Service de Pediatrie & Medecine Neonatale, Victor Jousselin General Hospital, 44, Avenue du President JF Kennedy, 28102 Dreux, France. E-mail: [email protected]
4
Pediatric Surgery Department, Rennes University Teaching Hospital, Rennes, France. 5 Pediatric Surgery Department, Angers University Teaching Hospital, Angers, France.
ß 2013 Wiley Periodicals, Inc.
Received 16 June 2013; Accepted 6 September 2013. DOI 10.1002/ppul.22920 Published online in Wiley Online Library (wileyonlinelibrary.com).
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The commonest classification based on the extent to which bronchopulmonary tissue is absent is that by Schneider and Schwalbe,1 it groups different forms into three categories: I—pulmonary agenesis corresponding to complete absence of lung, bronchus and vascular supply, II—pulmonary aplasia corresponds to absent lung tissue and pulmonary artery, but there is rudimentary bronchus coming off the trachea, and III—pulmonary hypoplasia in which there is hypoplastic lung and a rudimentary bronchial three. The left-sided pulmonary agenesis is the most common form, representing up to 70% of reported cases.2–6 Embryologically, the malformation results from lung development arrest occurring prior to the 26th day of fetal life with no precise cause found to date, to explain the phenomenon. Early antenatal diagnosis of this entity by the routine obstetrical ultrasound (US) is possible, and this tool represents the most frequent mode of discovery of the malformation. Pulmonary agenesis, in its unilateral form, is entirely compatible with life, its long-term prognosis remains, however, conditioned by the co-existence of associated malformations (most frequent of which are cardiac, gastrointestinal, and skeletal)1 that need to be well explored during antenatal life as this enables better organization of early postnatal care of the baby. We report four cases of pulmonary agenesis, two of which were diagnosed antenatally. Our aim is to describe the circumstances having led to the diagnosis, to report the follow-up and outcome of the four children and remind care providers of the importance of exploring associated malformations. Lastly, we wish to convey the message that pregnancy interruption should not, in our opinion, be systematically suggested to parents as unilateral form of this malformation is compatible with near normal life.
POPULATION AND METHODS
This is a retrospective collaborative study of four university teaching hospitals (Poitiers, Dijon, Angers, and Rennes). Search for medical records of children cared for (during the period running from January 1983 through December 2008) in each center with final diagnosis of pulmonary agenesis were launched through each hospital’s medical informatics department. Following informations were extracted from each medical file: maternal age, parity, pregnancy history with details on consumption of toxic substances (cigarette smoking, medicines, illicit drugs, etc.), term at delivery, baby’s gender, birth weight (BW), Apgar score, existence of respiratory distress and its management. Circumstances leading to diagnosis, malformation localization (right/left), result of caryotype if performed and co-existent malformations as evaluated by antenatal and postnatal US, results of both chest X-ray and thoracic scan and those of postnatal echocardiography. Appreciation of children’s present health status was evaluated by analyzing each child’s follow-up case record completed with a questionnaire sent to the family doctor. For the purpose of this study, the definition of pulmonary agenesis retained was that by Schneider and Schwabble1 according to which pulmonary agenesis corresponds to complete absence of lung tissue, bronchi, and pulmonary vessels (category 1). We, therefore, discarded cases of pulmonary hypoplasia in which there is persistence of rudimentary bronchial three without lung tissue or pulmonary artery. RESULTS
We identified seven cases from the four participating center, but only four cases corresponded to the definition of pulmonary agenesis. Characteristics of the study population are summarized in Table 1. Three children
TABLE 1— Study Population Characteristics and Co-Existent Malformations
Maternal age (years) Parity Delivery term (weeks þ days) Baby’s gender BW (g) Apgar score (1 and 5 min) Lung affected Caryotype Co-existing anomalies
Case 1
Case 2
Case 3
Case 4
29 P1 37 þ 2 M 2,580 10/10
30 P1 37 þ 5 M 2,600 10/10 RD þ MV Right N T6T7 fusion Hypospadias Scoliosis
26 P2 32 þ 6 F 1,630 10/10 TTN þ CPAP Right N Dextrocardia IVC and IAC
21 P2 39 M 3,350 10/10
Left N Hemivertebra T1 T1T2 synostosis Right club foot, Goldenhar syndrome
Right N Esophageal atresia Single umbilical artery Right renal agenesis, dextrocardia, cataract, IVC
N, normal; T, thoracic vertebra; RD, respiratory distress; MV, mechanical ventilation; TTN, transient tachypnea of newborn; CPAP, continuous airway pressure; IVC, interventricular communication; IAC, interauricular communication.
Pediatric Pulmonology
Unilateral Pulmonary Agenesis
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Fig. 2. Postnatal chest X-ray performed at age 1 month showing right hemithorax opacity (lung agenesis), dextrocardia, and T2 vertebra anomaly.
Fig. 1. T2-weighted images showing signs suggestive of pulmonary agenesis: (A) absent right lung parenchyma, (B) normal left lung tissue, (C) absence of signs in favor of diaphragmatic hernia.
were boys (M/F ratio 3:1), mean maternal age was 26.5 years (21–29 years), their pregnancies were uneventful. Three mothers had delivered at term, only one had delivered prematurely at 32 weeks þ 6 days, in a context of intra uterine growth retardation. All four babies adapted very well at birth, except case 2 who presented with respiratory distress leading to nasotracheal intubation and mechanical ventilation (3 days). Case 4 received nasal CPAP for transient tachypnea of newborn (36 hr). Pulmonary agenesis was diagnosed antenatally for 1 and 2 at 23rd and 30th weeks of gestation respectively. Fetal MRI was performed for case 2, to confirm the diagnosis (Fig. 1). Both cases 1 and 2 had fetal caryotype results of which were normal. In case 1, suspicion of congenital malformation was raised by finding of cardiac malposition and associated club foot at the obstetrical US performed at term 23 weeks þ 4 days of gestation. Repeat fetal US at 31st weeks revealed abnormal lung echogenecity. A fetal MRI was then performed at term 32 weeks, results were in favor of probable right-sided pulmonary agenesis causing dextrocardia, the left lung appeared normal, there were no signs in favor of diaphragmatic hernia, and no other malformation was visualized (Fig. 1). Fetal echocardiography was performed, it confirmed isolated dextrocardia. For cases 3 and 4 the diagnosis was reached postnatally, after chest X-rays that were performed subsequent to finding of asymmetrical
respiratory murmurs (case 3), and persistent vomiting occurring at day 2 of life (case 4). Figures 2 and 3 illustrate the results of chest X-ray and MRI performed in postnatal period (case 1). Other associated anomalies identified were cardiac, skeletal, craniofacial, and renal, summary in Table 1. Children’s Follow-Up
Children’s follow-up and care were individualized, and consisted of orthopedics and physiotherapy follow-up (case 1 with club foot), clinical and radiological surveillance for those with spinal anomalies (cases 1
Fig. 3. Images of (A) front view section, (B&D) sagittal section and (C) 3D reconstruction showing right pulmonary agenesis, (D) left lung hypertrophy, mediastinal shift into right hemithorax and two first ribs synostosis.
Pediatric Pulmonology
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and 2), respiratory function tests and cardiology surveillance (all cases). All four children received routine vaccinations according to French national immunization calendar, prevention of respiratory syncitial virus infection with Palizuvamab1 was administered to those aged less than 2 years. With 8 years follow-up, all the four children’s health status is satisfactory, their physical activity appropriate but requires regular chest physiotherapy for bronchial syndromes. Neurodevelopmentally, milestones acquisitions are within normal limits, school attendance is regular; only case 1 presents minimal right-sided motor deficiency that does not affect daily life and schooling. DISCUSSION
Pulmonary agenesis is extremely rare and results from the arrest, in early embryological life, of the lung development. Normal fetal pulmonary system begins to develop round the 22nd day with the appearance of a ventral bud on the primitive intestine. Between 26th and 28th days, esotracheal separation and bifurcation of the initial bud into two bronchial buds with corresponding vascular formation take place concomitantly with the transformation of aortic arches.7,8 The exact cause of pulmonary agenesis remains unknown, it seems to result from multiple factors that may be genetic, viral, teratogenic insults (vitamin A deficiency), and mechanical.4,9 Circumstances under which the malformation may be discovered are variable: previously the diagnosis was made at birth or during the neonatal period while investigating for signs of respiratory distress (cyanosis, dyspnea, stridor, respiratory distress, pulmonary asymmetry).3,4,6,10,11 The diagnosis was also suggested by a routine chest x-ray showing hemithoracic opacity with mediastinal shift.12 Cases revealed by recurrent pulmonary infections or non-specific pulmonary signs have also been reported3,4,6,13,14; in other cases the malformation was discovered fortuitously during childhood or adult life,15,16 first reported cases were discovered at autopsy. In recent years, progress achieved in obstetrical imaging has made early antenatal diagnosis possible with largest case series of 18 cases reported by Zhang et al.17 Cases have also been diagnosed antenatally as early as first,18 second,19–21 and third22 trimester of pregnancy. In our study, cases 1 and 2 were diagnosed at the second and third trimester, respectively. The fetal US finding that should raise the suspicion of pulmonary agenesis, although not pathognomonic, is the presence of mediastinal shift associated with unilateral abnormal lung echogenecity. Differential diagnoses to rule out are diaphragmatic hernia, cystic adenomatoid malformation of the lung, giant lobar emphysema, and congenital cardiac malformation such as situs inversus. To confirm the diagnosis, additional investigations are Pediatric Pulmonology
necessary: Color Doppler of fetal vascular anatomy is in favor of the malformation when it shows absent pulmonary artery and veins on the same side as abnormal lung echogenecity.22 In our two cases diagnosed antenatally, fetal MRI was of great contribution to the diagnosis. The literature seems to promote this tool as it allows the appreciation of fetal lung structural anomalies, but also permits the exclusion of other pathologies such as congenital diaphragmatic hernia, the association with pulmonary agenesis of which is detrimental to the outcome.7,8 Japanese authors suggest five fetal MRI findings that are strongly in favor of pulmonary agenesis: (1) absent right or left lung; (2) absent right or left main bronchus; (3) absent pulmonary artery; (4) left or right lung with homogeneous normal intensity; (5) abdominal contents in the abdominal cavity.23 Prognosis of pulmonary agenesis is mostly conditioned by the type of co-existent anomalies (summary in Table 2) that are present in 50–70% cases, and are commonly TABLE 2— Co-Existent Anomalies Reported With Pulmonary Agenesis (Maltz)4 Cardiac anomalies (14%)
Dextrocardia IVC, IAC Persistent Foramen ovale Left ventricular hypoplasia Fallot Tetralogy Gastrointestinal Gastroesophageal reflux anomalies (14%) Esophageal atresia Esophagotracheal fistula Pyloric stenosis Meckel diverticulum Anorectal malformations Skeletal anomalies Hemivertebrae (12%) Supernumerary ribs, hypoplasia, or fused vertebrae Radial ray deficit Bifid thumb Vascular malformations Persistent ductus arteriosus (9%) Abnormal venous return Left aberrant pulmonary artery Aortic arch interruption Arterial pulmonary hypertension Genitourinary (9%) Renal agenesis or ectopic kidney Duplicity or pyeloureteral ectopia Vesicoureteral reflux Horse shoe kidney Pulmonary malformations Contralateral pulmonary hypoplasia Tracheal compression and stenosis Ring shaped trachea Tracheomalacia Cranio-facial anomalies Facial microsomia Cleft lip and cleft palate Hypoplasia of maxilla or mandible Ears abnormalities Associated syndromes Velocardio-facial syndromes, Di George, and Goldenhar syndromes VACTERL association IVC, interventricular communication; IAC, interauricular communication.
Unilateral Pulmonary Agenesis
related to right-sided lung agenesis. The most reported anomalies are cardiac and gastrointestinal, followed in frequency by skeletal, vascular, craniofacial, and genitourinary.2–6,24 Of all, cardiac anomalies (aortic cross interruption, left ventricular hypoplasia, etc.) represent those with poorer prognosis as they may jeopardize the overall prognosis either directly or through their effects on the respiratory airways (compression by deviated aortic arch, dilatation of single pulmonary artery, or complex vascular rings).25–30 Persistent left superior vena cava may restrain tracheal growth,25,31,32 and intrinsic tracheobronchial anomalies such as tracheal stenosis and tracheomalacia may also lead to symptoms of tracheal compression. The right-sided anomaly by deviating the heart and the mediastinum leads to important vascular distortion that contributes to its poor prognosis.2,6 Management of pulmonary agenesis is essentially symptomatic, some of the associated cardiovascular anomalies may require surgery (aortopexy, section of vascular rings, resection of stenotic, and malacic bronchus) when they induce early airway complications.26,27,29,31,32 Important mediastinal shift may require the placement of expansion prosthesis18 or be corrected by diaphragmatic translocation.33,34 In our cases, a child with esophageal atresia and important gastro esophageal reflux received surgical treatment that improved feeding. Proper management of gastro esophageal reflux, present in over 50% infants with this anomaly, is indicated to
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5,35,36
preserve the respiratory functions. At birth most children have no respiratory distress, but when this is present, it is managed accordingly. We insist on the necessity for affected children to receive regular immunizations and those under age 2 years should receive Palizuvamab1 in prevention of respiratory syncitial virus, and regular Flu vaccination during the winter period. Pulmonary agenesis may be isolated or be, like our case 1, a part of a syndrome (velocardiofacial, Di Georges and Goldenhar)4,37–40 or an association such as VACTERL sequence (vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb anomalies).41,42 Some authors have reported a high association between pulmonary agenesis and some ipsilateral radial ray defects and/or craniofacial anomalies such as microtia and hemifacial microsomia. The ipsilateral situation of these anomalies along with the lung agenesis suggest that they may both result from an anomaly of aortic arch development.5,43,44 Outcome and Survival: Literature Review
We have a follow-up of over 8 years, all our four patients are doing well with normal growth and development as consequence of multi-disciplinary care that we consider a must for these patients (Table 3). The literature reports results that are variable, with old studies
TABLE 3— Literature Review (Antenatally Diagnosed Cases and Patients’ Outcome at Time of Publication)
Cases reported
Antenatal diagnosis (yes/no)
Side affected
Zhang, 2013 Meller, 201221 Kuwashima, 201023 Nonaka, 200922 Chiang, 201048 Langer, 200946 Chou, 200730
8 1 1 1 1 3 14
Yes Yes Yes Yes No No 5/14
7 Left, 11 right Right Right Right Right 2 Right, 1 left 4 Left, 10 right
Nazir, 20066 Eroglu, 200525 Go¨khan, 200549 Koseoglu, 200547 Gabarre, 200524 Downard, 200436 Ootaki, 200426 Managoli, 200450 Chen, 200344 Shivanand, 200314 Conway, 200239 Viora, 200220 Fitoz, 200140 Maymon, 200141 Kalache, 199719 Newman, 199727
3 1 1 1 1 1 3 1 1 2 1 1 1 1 1 4
No No No No Yes No No No Yes No Yes Yes No Yes Yes 2/4
3 Left Right Right Right Left Right 2 Right, 1 left Left Right Right/left Left Left Left Right Right 4 Right
Refs. 13
Follow-up and outcome (age/health status) 7 dead antenatally — — 1 year, uneventful 5 months, uneventful 4 months, 2 years, 4 years 9 deaths, 5 alive: (61 =2 years; 6 years; 34 =12 years; 32 =12 years; 5 months) uneventful 9 months; 6 years; 13 years Uneventful Death at day 3 30 years, uneventful 20 months 58 days 1 death; 2 alive (1 year and 6 months) Death at birth Death at day 2 — 2 years, uneventful Medical interruption of pregnancy — Medical interruption of pregnancy 3 months 1 death; 3 healthy
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being more pessimistic: mortality rate was as high as 50% before the age of 2 years for Maltz and Nadas,4 whereas Mardini and Nyhan2 reported a survival rate of 35% at age 40 years in patients with left-sided malformation versus only 10% in those with right-sided anomaly. In a study of 14 cases, Chou reported only 5 survivors, mortality was here also higher in those with right-sided malformation.30 As shown in Table 3 which summarizes some of reported cases, survival rate in the 43 cases was fairly good 27/41 (66%). Antenatally diagnosed cases remain, however, few as there were only 9/43 (21%) in this series; whether antenatal diagnosis improves survival rate is difficult to analyze. Two cases out nine diagnosed antenatally ended in medical termination of pregnancy.19,40 Our opinion is that pregnancy termination should not be systematic, but considered on individual basis after co-existent malformations have thoroughly been investigated and chances of survival assessed with parents. Pulmonary agenesis is compatible with normal life as shown by cases discovered fortuitously in adults with normal physical activities: three pregnant women (two aged 29 and 33 years) had their malformation diagnosed during pre-caesarian section anesthetic investigations (one with left-sided and the other two right-sided anomaly).15–18 A case of 77-year-old man with leftsided anomaly and persisting left superior vena cava has also been reported,30 lastly, a young asymptomatic 30-year-old man with right-sided malformation has been reported.47 CONCLUSION
Unilateral pulmonary agenesis is rare; its diagnosis can be made in early antenatal life with obstetrical US. Fetal MRI allows confirmation of the diagnosis and gives clues about differential diagnoses. Right-sided anomaly has the poorest prognosis due to greater distortion the great vessels and the airway, in addition to higher incidence of co-existent cardiac and vascular anomalies. Overall survival of children with left-sided form is compatible with normal life provided close multi-disciplinary followup is organized. Pregnancy interruption should not be systematic, but parents should received detailed informations about complications to expect and possibilities of postnatal care available. REFERENCES 1. Schneider P, Schwabble E. Die morphologic der missbildungen des menschen und der thiere, Vol. 3. Jena: G Fischer; 1912. pp 812–822. 2. Mardini MK, Nyhan WL. Agenesis of the lung. Report of four patients with unusual anomalies. Chest 1985;87:522–527. 3. Fokstuen S, Schinzel A. Unilateral lobar pulmonary agenesis in sibs. J Med Genet 2000;37:557–559. 4. Maltz DL, Nadas AS. Agenesis of the lung: Presentation of eight new cases and review of the literature. Pediatrics 1968;42:175–188.
Pediatric Pulmonology
5. Cunningham ML, Mann N. Pulmonary agenesis: A predictor of ipsilateral malformations. Am J Med Genet 1997;70:391–398. 6. Nazir Z, Qazi SH, Ahmed N, Atiq M, Biloo AG. Pulmonary agenesis—Vascular airway compression and gastroesophageal reflux influence outcome. J Pediatr Surg 2006;41:1165–1169. 7. Pasquali R, Potier A, Gorincour G. Fetal lung imaging. Gynecol Obstet Fertil 2008;36:587–602. 8. Kasprian G, Balassy C, Brugger P, Prayer D. MRI of normal and pathological fetal lung development. Eur J Radiol 2006;57: 261–270. 9. Maden M. Retinoids in lung development and regeneration. Curr Top Dev Biol 2004;61:153–189. 10. Guven S, Koyuturk Y, Cerrah Celayir A, Karadeniz L, Celikoglu S. An unusual cause of respiratory distress: Unilateral pulmonary agenesis. Arch Dis Child 2001;84:F197. 11. Borja MB, del Rio Camacho G, Orozco AL, Gil de San Vicente LP. et al. A first event of dyspnea in an infant. Chest 2000;18:1202– 1204. 12. Shaw TRD. Displacement of the heart caused by pulmonary agenesis. Heart 2002;88:277. 13. Nazaroglu H, Mete A, Bukte Y, Simkek M. Agenesis of the right lung presenting as a pulmonary infection. Clin Radiol 2002;57: 529–530. 14. Shivanand G, Mukhophadyay S, Vashisht S. An unusual cause of recurrent respiratory tract infection: Unilateral pulmonary agenesis. Eur J Radiol 2003;48:67–69. 15. Babita G, Rashmi M, Deb K. Combined spinal epidural anesthesia for cesarian section in a patient with left lung agenesis. Int J Obstet Anesth 2001;10:125–128. 16. Sicuranza G, Figueroa R. Pregnancy in a woman with unilateral lung agenesis. J Matern Fetal Neonatal Med 2004;15:418–420. 17. Zhang Y, Fan M, Ren W, Xie L, Ding C, Sun D, Wang Y, Guo Y. Prenatal diagnosis of fetal unilateral lung agenesis complicated with cardiac malposition. BMC Pregnancy Childbirth 2013;13:79. 18. Banerjee N, Roy KK, Takkar D. Pregnancy with unilateral lung agenesis. Acta Obstet Gynecol Scand 2000;79:896–897. 19. Kalache K, Chaoui R, Paris S, Bolmann R. Prenatal diagnosis of right lung agenesis using color Doppler and magnetic resonance imaging. Fetal Diagn Ther 1997;12:360–362. 20. Viora E, Sciarrone A, Bastonero S, et al. Prenatal diagnosis of isolated unilateral pulmonary agenesis in the second trimester. Ultrasound Obstet Gynecol 2002;19:206–207. 21. Meller CH, Morris K, Desai T, Kilby MD. Prenatal diagnosis of isolated right pulmonary agenesis using sonography alone. Case study and systematic literature review. J Ultrasound Med 2012; 31:2017–2023. 22. Nonaka T, Kikuchi A, Kido N, Takahashi Y, Yamada K, Usuda T, Takakuwa K, Tanaka K. Prenatal diagnosis of unilateral pulmonary agenesis in a pregnant women undergoing chronic hemodialysis due to chronic renal failure. Prenat Diagn 2009;29: 707–709. 23. Kuwashima S, Kaji Y. Fetal MR imaging diagnosis of pulmonary agenesis. Magn Reson Med Sci 2010;9:149–152. 24. Gabarre JA, Galindo Izquerdo A, Rasero Ponferrada M, Orbea Gallardo C, Puente Agueda JM, De la Fuente Perez P. Isolated unilateral pulmonary agenesis: Early prenatal diagnosis and longterm follow-up. J Ultrasound Med 2005;24:865–868. 25. Eroglu A, Alper F, Turkyilmaz A, Karaoglanoglu N, Okur A. Pulmonary agenesis associated with dextrocardia, sternal defects, and ectopic kidney. Pediatr Pulmonol 2005;40:547–549. 26. Ootaki Y, Yamaguchi N, Yoshimura N, Oka S. Pulmonary agenesis with congenital heart disease. Pediatr Cardiol 2004;25:145–148. 27. Newman B, Gondor M. MR evaluation of right pulmonary agenesis and vascular airway compression in pediatric patient. AJR Am J Roentgenol 1997;168:55–58.
Unilateral Pulmonary Agenesis 28. Lin JH, Chen SJ, Wu MH, Wang JK, Li YW, Lue HC. Right lung agenesis with left pulmonary artery sling. Pediatr Pulmonol 2000;29:239–241. 29. Wang W, Tovar JA, Eizaguirre I, Aldazabaal P. Airway obstruction and gastroesophageal reflux; an experimental study on the pathogenesis of this association. J Pediatr Surg 1993;28:995– 998. 30. Chou AK, Huang SC, Chen SJ, Huang PM, Wang JK, Chen YS, Chang CI, Chiu IS, Wu ET. Unilateral lung agenesis—Detrimental roles of surrounding vessels. Pediatr Pulmonol 2007;42:242– 248. 31. Meier M. Agenesis of the left lung in combination with a persistent left superior vena cava and al cor triatriatum sinister in a 77-yearold man. Pneumologie 2000;54:249–251. 32. Weber TR, Connors RT, Tracy TF. Congenital tracheal stenosis with unilateral pulmonary agenesis. Ann Surg 1991;213:70–74. 33. Dohlemann C, Mantel K, Schneider K, Guntner M, Kreuzer E, Hecker WC. Deviated trachea in hypoplasia and aplasia of the right lung: Airway obstruction and its release by aortopexy. J Pediatr Surg 1990;25:290–293. 34. Krivchenya DU, Dubrovin AG, Krivchenya TD, Khursin VN, Lysak CV. Aplasia of the right lung in a 4-year-old child: Surgical stabilization of the mediastinum by diaphragm translocation leading to complete recovery from respiratory distress syndrome. J Pediatr Surg 2000;35:1499–1502. 35. Sheth NP. Aplasia of the right lung in a 4-year-old child: Surgical stabilization of the mediastinum by diaphragm translocation. J Pediatr Surg 2001;36:1606–1607. 36. Downard CD, Kim HB, Laningham F, Fishman SJ. Esophageal atresia, duodenal atresia, and unilateral lung agenesis: A case report. J Pediatr Surg 2004;39:1283–1285. 37. Steadland KM, Langham MR, Jr., Greene MA, Bagwell CE, Kays DW, Talbert JL. Unilateral pulmonary agenesis, esophageal atresia, and distal tracheoesophageal fistula. Ann Thorac Surg 1995;59:511–513. 38. Osborne J, Masel J, McCredie J. A spectrum of skeletal anomalies associated with pulmonary agenesis: Possible neural crest injuries. Pediatr Radiol 1989;19:425–432.
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39. Conway K, Gibson R, Perkins J, Cunningham ML. Pulmonary agenesis: Expansion of the VCFS phenotype. Am J Med Genet 2002;113:89–92. 40. Fitoz S, Ucar T, Erden A, Gunlemez A. DiGeorge syndrome associated with left lung aplasia. Br J Radiol 2001;74:764–766. 41. Maymon R, Schneider D, Hegesh J, et al. Antenatal sonographic findings of right pulmonary agenesis with ipsilateral microtia: A possible new laterality association. Prenat Diagn 2001;21:125– 128. 42. Milani D, Selicorni A. Right pulmonary agenesis with ipsilateral microtia: A new laterality association or part of the oculoauriculovertebral spectrum? Prenat Diagn 2002;22:1053–1054. 43. Knowles S, Thomas RM, Lindenbaum RH, Keeling JW, Winter RM. Pulmonary agenesis as a part of the VACTERL sequence. Arch Dis Child 1988;63:723–726. 44. Chen CP, Shih JC, Chang JH, Wang W. Prenatal diagnosis of right pulmonary agenesis associated with VACTERL sequence. Prenat Diagn 2003;23:515–518. 45. Aggarwal AN, Gupta D, Jindal SK. Unilateral pulmonary agenesis with ipsilateral musculoskeletal anomalies. J Assoc Physicians India 2002;50:1324–1326. 46. Langer M, Chiu PP, Kim PC. Congenital and acquired single-lung patients: Long-term follow-up reveals high mortality risk. J Pediatr Surg 2009;44:100–105. 47. Ko¨seog˘lu N, Ucan ES, Cavdar C. Right lung agenesis and left lung bronchiectasis. Respir Med Extra 2005;1:110–112. 48. Chiang LL, Chiu SN, Huang SC, Chen SJ. Unilateral left lung agenesis with crossed-ectopic right lower lobe combined tricuspid atresia diagnosed by ECG gated computed tomography. J Thorac Cardiovasc Surg 2010;139:e110–e111. ¨ zbilim G, Bozova S, Gu¨ra A, Ongun H, Mihci E, 49. Go¨khan GA, O Arslan G. Unilateral pulmonary agenesis associated with colloidal goiter in a newborn: a case report. Turkish J Pediatr 2005;47:295– 297. 50. Managoli S, Chaturvedi P, Vilhekar KY, Gagane N. Unilateral pulmonary agenesis and renal anomalies associated with In situ neuroblastoma of the adrenal gland. Indian J Pediatr 2004;71: 545–547.
Pediatric Pulmonology
Case Report
Unilateral Pulmonary Agenesis: A Report of Four Cases, Two Diagnosed Antenatally and Literature Review S. Kayemba-Kay’s, MBBS, MD,1* V. Couvrat-Carcauzon, MD,2 V. Goua, MD,3 G. Podevin, PhD,4 M. Marteau, MD,5 E. Sapin, PhD,6 and G. Levard, PhD2 Summary. Pulmonary agenesis is a rare congenital malformation of lung development defined as complete absence of lung tissues, bronchi, and pulmonary vessels; it may be uni- or bilateral. The right-sided form carries the poorest prognosis due to severity of co-existent anomalies. Its diagnostic circumstances are variables: first reported cases were diagnosed at autopsy, but early postnatal as well as fortuitous discovery have been reported. In recent years, progress in obstetrical imaging has made antenatal diagnosis possible so that fetal ultrasound and MRI allow early diagnosis and refinement by permitting the elimination of differential diagnoses (diaphragmatic hernia, cystic adenomatoid malformation of the lung, giant lobar emphysema, and situs inversus). This anomaly is compatible with normal life provided co-existent malformations are thoroughly investigated and managed in a multidisciplinary setting. We report four cases of lung agenesis two of which were diagnosed antenatally at 23rd and 30th weeks of gestation respectively. Our aim is to describe the circumstances having led to diagnosis and report both follow-up and outcome of our patients. Pediatr Pulmonol. ß 2013 Wiley Periodicals, Inc. Key words: pulmonary agenesis; antenatal diagnosis; prognosis; co-existent anomalies; fetal MRI. Funding source: none reported
Pulmonary agenesis is a rare congenital malformation of lung development that was first described by De Pozze in 1673 from a necropsy of an adult female. Defined as complete absence of lung tissues, bronchi, and pulmonary
vessels,1 it may be unilateral or bilateral, partial, or complete. With about 300 cases reported in the literature, this malformation has an estimated frequency between 1/10,000 to 1/15,000 autopsies, its occurrence is usually sporadic in most of cases, but parental consanguinity has been reported by Mardini and Nyhan.2
1 Neonatal Medicine Section, Service de Pediatrie & Medecine Neonatale, Victor Jousselin Hospital, Dreux, France.
6 Pediatric Surgery Department, Dijon University Teaching Hospital, Dijon, France.
2
Conflict of interest: None.
INTRODUCTION
Pediatric Surgery Section, Departement Medico-Chirurgical de Pediatrie, Poitiers University Teaching Hospital, Poitiers, France.
3
Antenatal Diagnosis Section, Obstetrics & Gynecology Department, Poitiers University Teaching Hospital, Poitiers, France.
Correspondence to: S. Kayemba-Kay’s, Unite de Neonatologie, Service de Pediatrie & Medecine Neonatale, Victor Jousselin General Hospital, 44, Avenue du President JF Kennedy, 28102 Dreux, France. E-mail: [email protected]
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Pediatric Surgery Department, Rennes University Teaching Hospital, Rennes, France. 5 Pediatric Surgery Department, Angers University Teaching Hospital, Angers, France.
ß 2013 Wiley Periodicals, Inc.
Received 16 June 2013; Accepted 6 September 2013. DOI 10.1002/ppul.22920 Published online in Wiley Online Library (wileyonlinelibrary.com).
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The commonest classification based on the extent to which bronchopulmonary tissue is absent is that by Schneider and Schwalbe,1 it groups different forms into three categories: I—pulmonary agenesis corresponding to complete absence of lung, bronchus and vascular supply, II—pulmonary aplasia corresponds to absent lung tissue and pulmonary artery, but there is rudimentary bronchus coming off the trachea, and III—pulmonary hypoplasia in which there is hypoplastic lung and a rudimentary bronchial three. The left-sided pulmonary agenesis is the most common form, representing up to 70% of reported cases.2–6 Embryologically, the malformation results from lung development arrest occurring prior to the 26th day of fetal life with no precise cause found to date, to explain the phenomenon. Early antenatal diagnosis of this entity by the routine obstetrical ultrasound (US) is possible, and this tool represents the most frequent mode of discovery of the malformation. Pulmonary agenesis, in its unilateral form, is entirely compatible with life, its long-term prognosis remains, however, conditioned by the co-existence of associated malformations (most frequent of which are cardiac, gastrointestinal, and skeletal)1 that need to be well explored during antenatal life as this enables better organization of early postnatal care of the baby. We report four cases of pulmonary agenesis, two of which were diagnosed antenatally. Our aim is to describe the circumstances having led to the diagnosis, to report the follow-up and outcome of the four children and remind care providers of the importance of exploring associated malformations. Lastly, we wish to convey the message that pregnancy interruption should not, in our opinion, be systematically suggested to parents as unilateral form of this malformation is compatible with near normal life.
POPULATION AND METHODS
This is a retrospective collaborative study of four university teaching hospitals (Poitiers, Dijon, Angers, and Rennes). Search for medical records of children cared for (during the period running from January 1983 through December 2008) in each center with final diagnosis of pulmonary agenesis were launched through each hospital’s medical informatics department. Following informations were extracted from each medical file: maternal age, parity, pregnancy history with details on consumption of toxic substances (cigarette smoking, medicines, illicit drugs, etc.), term at delivery, baby’s gender, birth weight (BW), Apgar score, existence of respiratory distress and its management. Circumstances leading to diagnosis, malformation localization (right/left), result of caryotype if performed and co-existent malformations as evaluated by antenatal and postnatal US, results of both chest X-ray and thoracic scan and those of postnatal echocardiography. Appreciation of children’s present health status was evaluated by analyzing each child’s follow-up case record completed with a questionnaire sent to the family doctor. For the purpose of this study, the definition of pulmonary agenesis retained was that by Schneider and Schwabble1 according to which pulmonary agenesis corresponds to complete absence of lung tissue, bronchi, and pulmonary vessels (category 1). We, therefore, discarded cases of pulmonary hypoplasia in which there is persistence of rudimentary bronchial three without lung tissue or pulmonary artery. RESULTS
We identified seven cases from the four participating center, but only four cases corresponded to the definition of pulmonary agenesis. Characteristics of the study population are summarized in Table 1. Three children
TABLE 1— Study Population Characteristics and Co-Existent Malformations
Maternal age (years) Parity Delivery term (weeks þ days) Baby’s gender BW (g) Apgar score (1 and 5 min) Lung affected Caryotype Co-existing anomalies
Case 1
Case 2
Case 3
Case 4
29 P1 37 þ 2 M 2,580 10/10
30 P1 37 þ 5 M 2,600 10/10 RD þ MV Right N T6T7 fusion Hypospadias Scoliosis
26 P2 32 þ 6 F 1,630 10/10 TTN þ CPAP Right N Dextrocardia IVC and IAC
21 P2 39 M 3,350 10/10
Left N Hemivertebra T1 T1T2 synostosis Right club foot, Goldenhar syndrome
Right N Esophageal atresia Single umbilical artery Right renal agenesis, dextrocardia, cataract, IVC
N, normal; T, thoracic vertebra; RD, respiratory distress; MV, mechanical ventilation; TTN, transient tachypnea of newborn; CPAP, continuous airway pressure; IVC, interventricular communication; IAC, interauricular communication.
Pediatric Pulmonology
Unilateral Pulmonary Agenesis
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Fig. 2. Postnatal chest X-ray performed at age 1 month showing right hemithorax opacity (lung agenesis), dextrocardia, and T2 vertebra anomaly.
Fig. 1. T2-weighted images showing signs suggestive of pulmonary agenesis: (A) absent right lung parenchyma, (B) normal left lung tissue, (C) absence of signs in favor of diaphragmatic hernia.
were boys (M/F ratio 3:1), mean maternal age was 26.5 years (21–29 years), their pregnancies were uneventful. Three mothers had delivered at term, only one had delivered prematurely at 32 weeks þ 6 days, in a context of intra uterine growth retardation. All four babies adapted very well at birth, except case 2 who presented with respiratory distress leading to nasotracheal intubation and mechanical ventilation (3 days). Case 4 received nasal CPAP for transient tachypnea of newborn (36 hr). Pulmonary agenesis was diagnosed antenatally for 1 and 2 at 23rd and 30th weeks of gestation respectively. Fetal MRI was performed for case 2, to confirm the diagnosis (Fig. 1). Both cases 1 and 2 had fetal caryotype results of which were normal. In case 1, suspicion of congenital malformation was raised by finding of cardiac malposition and associated club foot at the obstetrical US performed at term 23 weeks þ 4 days of gestation. Repeat fetal US at 31st weeks revealed abnormal lung echogenecity. A fetal MRI was then performed at term 32 weeks, results were in favor of probable right-sided pulmonary agenesis causing dextrocardia, the left lung appeared normal, there were no signs in favor of diaphragmatic hernia, and no other malformation was visualized (Fig. 1). Fetal echocardiography was performed, it confirmed isolated dextrocardia. For cases 3 and 4 the diagnosis was reached postnatally, after chest X-rays that were performed subsequent to finding of asymmetrical
respiratory murmurs (case 3), and persistent vomiting occurring at day 2 of life (case 4). Figures 2 and 3 illustrate the results of chest X-ray and MRI performed in postnatal period (case 1). Other associated anomalies identified were cardiac, skeletal, craniofacial, and renal, summary in Table 1. Children’s Follow-Up
Children’s follow-up and care were individualized, and consisted of orthopedics and physiotherapy follow-up (case 1 with club foot), clinical and radiological surveillance for those with spinal anomalies (cases 1
Fig. 3. Images of (A) front view section, (B&D) sagittal section and (C) 3D reconstruction showing right pulmonary agenesis, (D) left lung hypertrophy, mediastinal shift into right hemithorax and two first ribs synostosis.
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and 2), respiratory function tests and cardiology surveillance (all cases). All four children received routine vaccinations according to French national immunization calendar, prevention of respiratory syncitial virus infection with Palizuvamab1 was administered to those aged less than 2 years. With 8 years follow-up, all the four children’s health status is satisfactory, their physical activity appropriate but requires regular chest physiotherapy for bronchial syndromes. Neurodevelopmentally, milestones acquisitions are within normal limits, school attendance is regular; only case 1 presents minimal right-sided motor deficiency that does not affect daily life and schooling. DISCUSSION
Pulmonary agenesis is extremely rare and results from the arrest, in early embryological life, of the lung development. Normal fetal pulmonary system begins to develop round the 22nd day with the appearance of a ventral bud on the primitive intestine. Between 26th and 28th days, esotracheal separation and bifurcation of the initial bud into two bronchial buds with corresponding vascular formation take place concomitantly with the transformation of aortic arches.7,8 The exact cause of pulmonary agenesis remains unknown, it seems to result from multiple factors that may be genetic, viral, teratogenic insults (vitamin A deficiency), and mechanical.4,9 Circumstances under which the malformation may be discovered are variable: previously the diagnosis was made at birth or during the neonatal period while investigating for signs of respiratory distress (cyanosis, dyspnea, stridor, respiratory distress, pulmonary asymmetry).3,4,6,10,11 The diagnosis was also suggested by a routine chest x-ray showing hemithoracic opacity with mediastinal shift.12 Cases revealed by recurrent pulmonary infections or non-specific pulmonary signs have also been reported3,4,6,13,14; in other cases the malformation was discovered fortuitously during childhood or adult life,15,16 first reported cases were discovered at autopsy. In recent years, progress achieved in obstetrical imaging has made early antenatal diagnosis possible with largest case series of 18 cases reported by Zhang et al.17 Cases have also been diagnosed antenatally as early as first,18 second,19–21 and third22 trimester of pregnancy. In our study, cases 1 and 2 were diagnosed at the second and third trimester, respectively. The fetal US finding that should raise the suspicion of pulmonary agenesis, although not pathognomonic, is the presence of mediastinal shift associated with unilateral abnormal lung echogenecity. Differential diagnoses to rule out are diaphragmatic hernia, cystic adenomatoid malformation of the lung, giant lobar emphysema, and congenital cardiac malformation such as situs inversus. To confirm the diagnosis, additional investigations are Pediatric Pulmonology
necessary: Color Doppler of fetal vascular anatomy is in favor of the malformation when it shows absent pulmonary artery and veins on the same side as abnormal lung echogenecity.22 In our two cases diagnosed antenatally, fetal MRI was of great contribution to the diagnosis. The literature seems to promote this tool as it allows the appreciation of fetal lung structural anomalies, but also permits the exclusion of other pathologies such as congenital diaphragmatic hernia, the association with pulmonary agenesis of which is detrimental to the outcome.7,8 Japanese authors suggest five fetal MRI findings that are strongly in favor of pulmonary agenesis: (1) absent right or left lung; (2) absent right or left main bronchus; (3) absent pulmonary artery; (4) left or right lung with homogeneous normal intensity; (5) abdominal contents in the abdominal cavity.23 Prognosis of pulmonary agenesis is mostly conditioned by the type of co-existent anomalies (summary in Table 2) that are present in 50–70% cases, and are commonly TABLE 2— Co-Existent Anomalies Reported With Pulmonary Agenesis (Maltz)4 Cardiac anomalies (14%)
Dextrocardia IVC, IAC Persistent Foramen ovale Left ventricular hypoplasia Fallot Tetralogy Gastrointestinal Gastroesophageal reflux anomalies (14%) Esophageal atresia Esophagotracheal fistula Pyloric stenosis Meckel diverticulum Anorectal malformations Skeletal anomalies Hemivertebrae (12%) Supernumerary ribs, hypoplasia, or fused vertebrae Radial ray deficit Bifid thumb Vascular malformations Persistent ductus arteriosus (9%) Abnormal venous return Left aberrant pulmonary artery Aortic arch interruption Arterial pulmonary hypertension Genitourinary (9%) Renal agenesis or ectopic kidney Duplicity or pyeloureteral ectopia Vesicoureteral reflux Horse shoe kidney Pulmonary malformations Contralateral pulmonary hypoplasia Tracheal compression and stenosis Ring shaped trachea Tracheomalacia Cranio-facial anomalies Facial microsomia Cleft lip and cleft palate Hypoplasia of maxilla or mandible Ears abnormalities Associated syndromes Velocardio-facial syndromes, Di George, and Goldenhar syndromes VACTERL association IVC, interventricular communication; IAC, interauricular communication.
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related to right-sided lung agenesis. The most reported anomalies are cardiac and gastrointestinal, followed in frequency by skeletal, vascular, craniofacial, and genitourinary.2–6,24 Of all, cardiac anomalies (aortic cross interruption, left ventricular hypoplasia, etc.) represent those with poorer prognosis as they may jeopardize the overall prognosis either directly or through their effects on the respiratory airways (compression by deviated aortic arch, dilatation of single pulmonary artery, or complex vascular rings).25–30 Persistent left superior vena cava may restrain tracheal growth,25,31,32 and intrinsic tracheobronchial anomalies such as tracheal stenosis and tracheomalacia may also lead to symptoms of tracheal compression. The right-sided anomaly by deviating the heart and the mediastinum leads to important vascular distortion that contributes to its poor prognosis.2,6 Management of pulmonary agenesis is essentially symptomatic, some of the associated cardiovascular anomalies may require surgery (aortopexy, section of vascular rings, resection of stenotic, and malacic bronchus) when they induce early airway complications.26,27,29,31,32 Important mediastinal shift may require the placement of expansion prosthesis18 or be corrected by diaphragmatic translocation.33,34 In our cases, a child with esophageal atresia and important gastro esophageal reflux received surgical treatment that improved feeding. Proper management of gastro esophageal reflux, present in over 50% infants with this anomaly, is indicated to
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5,35,36
preserve the respiratory functions. At birth most children have no respiratory distress, but when this is present, it is managed accordingly. We insist on the necessity for affected children to receive regular immunizations and those under age 2 years should receive Palizuvamab1 in prevention of respiratory syncitial virus, and regular Flu vaccination during the winter period. Pulmonary agenesis may be isolated or be, like our case 1, a part of a syndrome (velocardiofacial, Di Georges and Goldenhar)4,37–40 or an association such as VACTERL sequence (vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb anomalies).41,42 Some authors have reported a high association between pulmonary agenesis and some ipsilateral radial ray defects and/or craniofacial anomalies such as microtia and hemifacial microsomia. The ipsilateral situation of these anomalies along with the lung agenesis suggest that they may both result from an anomaly of aortic arch development.5,43,44 Outcome and Survival: Literature Review
We have a follow-up of over 8 years, all our four patients are doing well with normal growth and development as consequence of multi-disciplinary care that we consider a must for these patients (Table 3). The literature reports results that are variable, with old studies
TABLE 3— Literature Review (Antenatally Diagnosed Cases and Patients’ Outcome at Time of Publication)
Cases reported
Antenatal diagnosis (yes/no)
Side affected
Zhang, 2013 Meller, 201221 Kuwashima, 201023 Nonaka, 200922 Chiang, 201048 Langer, 200946 Chou, 200730
8 1 1 1 1 3 14
Yes Yes Yes Yes No No 5/14
7 Left, 11 right Right Right Right Right 2 Right, 1 left 4 Left, 10 right
Nazir, 20066 Eroglu, 200525 Go¨khan, 200549 Koseoglu, 200547 Gabarre, 200524 Downard, 200436 Ootaki, 200426 Managoli, 200450 Chen, 200344 Shivanand, 200314 Conway, 200239 Viora, 200220 Fitoz, 200140 Maymon, 200141 Kalache, 199719 Newman, 199727
3 1 1 1 1 1 3 1 1 2 1 1 1 1 1 4
No No No No Yes No No No Yes No Yes Yes No Yes Yes 2/4
3 Left Right Right Right Left Right 2 Right, 1 left Left Right Right/left Left Left Left Right Right 4 Right
Refs. 13
Follow-up and outcome (age/health status) 7 dead antenatally — — 1 year, uneventful 5 months, uneventful 4 months, 2 years, 4 years 9 deaths, 5 alive: (61 =2 years; 6 years; 34 =12 years; 32 =12 years; 5 months) uneventful 9 months; 6 years; 13 years Uneventful Death at day 3 30 years, uneventful 20 months 58 days 1 death; 2 alive (1 year and 6 months) Death at birth Death at day 2 — 2 years, uneventful Medical interruption of pregnancy — Medical interruption of pregnancy 3 months 1 death; 3 healthy
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being more pessimistic: mortality rate was as high as 50% before the age of 2 years for Maltz and Nadas,4 whereas Mardini and Nyhan2 reported a survival rate of 35% at age 40 years in patients with left-sided malformation versus only 10% in those with right-sided anomaly. In a study of 14 cases, Chou reported only 5 survivors, mortality was here also higher in those with right-sided malformation.30 As shown in Table 3 which summarizes some of reported cases, survival rate in the 43 cases was fairly good 27/41 (66%). Antenatally diagnosed cases remain, however, few as there were only 9/43 (21%) in this series; whether antenatal diagnosis improves survival rate is difficult to analyze. Two cases out nine diagnosed antenatally ended in medical termination of pregnancy.19,40 Our opinion is that pregnancy termination should not be systematic, but considered on individual basis after co-existent malformations have thoroughly been investigated and chances of survival assessed with parents. Pulmonary agenesis is compatible with normal life as shown by cases discovered fortuitously in adults with normal physical activities: three pregnant women (two aged 29 and 33 years) had their malformation diagnosed during pre-caesarian section anesthetic investigations (one with left-sided and the other two right-sided anomaly).15–18 A case of 77-year-old man with leftsided anomaly and persisting left superior vena cava has also been reported,30 lastly, a young asymptomatic 30-year-old man with right-sided malformation has been reported.47 CONCLUSION
Unilateral pulmonary agenesis is rare; its diagnosis can be made in early antenatal life with obstetrical US. Fetal MRI allows confirmation of the diagnosis and gives clues about differential diagnoses. Right-sided anomaly has the poorest prognosis due to greater distortion the great vessels and the airway, in addition to higher incidence of co-existent cardiac and vascular anomalies. Overall survival of children with left-sided form is compatible with normal life provided close multi-disciplinary followup is organized. Pregnancy interruption should not be systematic, but parents should received detailed informations about complications to expect and possibilities of postnatal care available. REFERENCES 1. Schneider P, Schwabble E. Die morphologic der missbildungen des menschen und der thiere, Vol. 3. Jena: G Fischer; 1912. pp 812–822. 2. Mardini MK, Nyhan WL. Agenesis of the lung. Report of four patients with unusual anomalies. Chest 1985;87:522–527. 3. Fokstuen S, Schinzel A. Unilateral lobar pulmonary agenesis in sibs. J Med Genet 2000;37:557–559. 4. Maltz DL, Nadas AS. Agenesis of the lung: Presentation of eight new cases and review of the literature. Pediatrics 1968;42:175–188.
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5. Cunningham ML, Mann N. Pulmonary agenesis: A predictor of ipsilateral malformations. Am J Med Genet 1997;70:391–398. 6. Nazir Z, Qazi SH, Ahmed N, Atiq M, Biloo AG. Pulmonary agenesis—Vascular airway compression and gastroesophageal reflux influence outcome. J Pediatr Surg 2006;41:1165–1169. 7. Pasquali R, Potier A, Gorincour G. Fetal lung imaging. Gynecol Obstet Fertil 2008;36:587–602. 8. Kasprian G, Balassy C, Brugger P, Prayer D. MRI of normal and pathological fetal lung development. Eur J Radiol 2006;57: 261–270. 9. Maden M. Retinoids in lung development and regeneration. Curr Top Dev Biol 2004;61:153–189. 10. Guven S, Koyuturk Y, Cerrah Celayir A, Karadeniz L, Celikoglu S. An unusual cause of respiratory distress: Unilateral pulmonary agenesis. Arch Dis Child 2001;84:F197. 11. Borja MB, del Rio Camacho G, Orozco AL, Gil de San Vicente LP. et al. A first event of dyspnea in an infant. Chest 2000;18:1202– 1204. 12. Shaw TRD. Displacement of the heart caused by pulmonary agenesis. Heart 2002;88:277. 13. Nazaroglu H, Mete A, Bukte Y, Simkek M. Agenesis of the right lung presenting as a pulmonary infection. Clin Radiol 2002;57: 529–530. 14. Shivanand G, Mukhophadyay S, Vashisht S. An unusual cause of recurrent respiratory tract infection: Unilateral pulmonary agenesis. Eur J Radiol 2003;48:67–69. 15. Babita G, Rashmi M, Deb K. Combined spinal epidural anesthesia for cesarian section in a patient with left lung agenesis. Int J Obstet Anesth 2001;10:125–128. 16. Sicuranza G, Figueroa R. Pregnancy in a woman with unilateral lung agenesis. J Matern Fetal Neonatal Med 2004;15:418–420. 17. Zhang Y, Fan M, Ren W, Xie L, Ding C, Sun D, Wang Y, Guo Y. Prenatal diagnosis of fetal unilateral lung agenesis complicated with cardiac malposition. BMC Pregnancy Childbirth 2013;13:79. 18. Banerjee N, Roy KK, Takkar D. Pregnancy with unilateral lung agenesis. Acta Obstet Gynecol Scand 2000;79:896–897. 19. Kalache K, Chaoui R, Paris S, Bolmann R. Prenatal diagnosis of right lung agenesis using color Doppler and magnetic resonance imaging. Fetal Diagn Ther 1997;12:360–362. 20. Viora E, Sciarrone A, Bastonero S, et al. Prenatal diagnosis of isolated unilateral pulmonary agenesis in the second trimester. Ultrasound Obstet Gynecol 2002;19:206–207. 21. Meller CH, Morris K, Desai T, Kilby MD. Prenatal diagnosis of isolated right pulmonary agenesis using sonography alone. Case study and systematic literature review. J Ultrasound Med 2012; 31:2017–2023. 22. Nonaka T, Kikuchi A, Kido N, Takahashi Y, Yamada K, Usuda T, Takakuwa K, Tanaka K. Prenatal diagnosis of unilateral pulmonary agenesis in a pregnant women undergoing chronic hemodialysis due to chronic renal failure. Prenat Diagn 2009;29: 707–709. 23. Kuwashima S, Kaji Y. Fetal MR imaging diagnosis of pulmonary agenesis. Magn Reson Med Sci 2010;9:149–152. 24. Gabarre JA, Galindo Izquerdo A, Rasero Ponferrada M, Orbea Gallardo C, Puente Agueda JM, De la Fuente Perez P. Isolated unilateral pulmonary agenesis: Early prenatal diagnosis and longterm follow-up. J Ultrasound Med 2005;24:865–868. 25. Eroglu A, Alper F, Turkyilmaz A, Karaoglanoglu N, Okur A. Pulmonary agenesis associated with dextrocardia, sternal defects, and ectopic kidney. Pediatr Pulmonol 2005;40:547–549. 26. Ootaki Y, Yamaguchi N, Yoshimura N, Oka S. Pulmonary agenesis with congenital heart disease. Pediatr Cardiol 2004;25:145–148. 27. Newman B, Gondor M. MR evaluation of right pulmonary agenesis and vascular airway compression in pediatric patient. AJR Am J Roentgenol 1997;168:55–58.
Unilateral Pulmonary Agenesis 28. Lin JH, Chen SJ, Wu MH, Wang JK, Li YW, Lue HC. Right lung agenesis with left pulmonary artery sling. Pediatr Pulmonol 2000;29:239–241. 29. Wang W, Tovar JA, Eizaguirre I, Aldazabaal P. Airway obstruction and gastroesophageal reflux; an experimental study on the pathogenesis of this association. J Pediatr Surg 1993;28:995– 998. 30. Chou AK, Huang SC, Chen SJ, Huang PM, Wang JK, Chen YS, Chang CI, Chiu IS, Wu ET. Unilateral lung agenesis—Detrimental roles of surrounding vessels. Pediatr Pulmonol 2007;42:242– 248. 31. Meier M. Agenesis of the left lung in combination with a persistent left superior vena cava and al cor triatriatum sinister in a 77-yearold man. Pneumologie 2000;54:249–251. 32. Weber TR, Connors RT, Tracy TF. Congenital tracheal stenosis with unilateral pulmonary agenesis. Ann Surg 1991;213:70–74. 33. Dohlemann C, Mantel K, Schneider K, Guntner M, Kreuzer E, Hecker WC. Deviated trachea in hypoplasia and aplasia of the right lung: Airway obstruction and its release by aortopexy. J Pediatr Surg 1990;25:290–293. 34. Krivchenya DU, Dubrovin AG, Krivchenya TD, Khursin VN, Lysak CV. Aplasia of the right lung in a 4-year-old child: Surgical stabilization of the mediastinum by diaphragm translocation leading to complete recovery from respiratory distress syndrome. J Pediatr Surg 2000;35:1499–1502. 35. Sheth NP. Aplasia of the right lung in a 4-year-old child: Surgical stabilization of the mediastinum by diaphragm translocation. J Pediatr Surg 2001;36:1606–1607. 36. Downard CD, Kim HB, Laningham F, Fishman SJ. Esophageal atresia, duodenal atresia, and unilateral lung agenesis: A case report. J Pediatr Surg 2004;39:1283–1285. 37. Steadland KM, Langham MR, Jr., Greene MA, Bagwell CE, Kays DW, Talbert JL. Unilateral pulmonary agenesis, esophageal atresia, and distal tracheoesophageal fistula. Ann Thorac Surg 1995;59:511–513. 38. Osborne J, Masel J, McCredie J. A spectrum of skeletal anomalies associated with pulmonary agenesis: Possible neural crest injuries. Pediatr Radiol 1989;19:425–432.
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39. Conway K, Gibson R, Perkins J, Cunningham ML. Pulmonary agenesis: Expansion of the VCFS phenotype. Am J Med Genet 2002;113:89–92. 40. Fitoz S, Ucar T, Erden A, Gunlemez A. DiGeorge syndrome associated with left lung aplasia. Br J Radiol 2001;74:764–766. 41. Maymon R, Schneider D, Hegesh J, et al. Antenatal sonographic findings of right pulmonary agenesis with ipsilateral microtia: A possible new laterality association. Prenat Diagn 2001;21:125– 128. 42. Milani D, Selicorni A. Right pulmonary agenesis with ipsilateral microtia: A new laterality association or part of the oculoauriculovertebral spectrum? Prenat Diagn 2002;22:1053–1054. 43. Knowles S, Thomas RM, Lindenbaum RH, Keeling JW, Winter RM. Pulmonary agenesis as a part of the VACTERL sequence. Arch Dis Child 1988;63:723–726. 44. Chen CP, Shih JC, Chang JH, Wang W. Prenatal diagnosis of right pulmonary agenesis associated with VACTERL sequence. Prenat Diagn 2003;23:515–518. 45. Aggarwal AN, Gupta D, Jindal SK. Unilateral pulmonary agenesis with ipsilateral musculoskeletal anomalies. J Assoc Physicians India 2002;50:1324–1326. 46. Langer M, Chiu PP, Kim PC. Congenital and acquired single-lung patients: Long-term follow-up reveals high mortality risk. J Pediatr Surg 2009;44:100–105. 47. Ko¨seog˘lu N, Ucan ES, Cavdar C. Right lung agenesis and left lung bronchiectasis. Respir Med Extra 2005;1:110–112. 48. Chiang LL, Chiu SN, Huang SC, Chen SJ. Unilateral left lung agenesis with crossed-ectopic right lower lobe combined tricuspid atresia diagnosed by ECG gated computed tomography. J Thorac Cardiovasc Surg 2010;139:e110–e111. ¨ zbilim G, Bozova S, Gu¨ra A, Ongun H, Mihci E, 49. Go¨khan GA, O Arslan G. Unilateral pulmonary agenesis associated with colloidal goiter in a newborn: a case report. Turkish J Pediatr 2005;47:295– 297. 50. Managoli S, Chaturvedi P, Vilhekar KY, Gagane N. Unilateral pulmonary agenesis and renal anomalies associated with In situ neuroblastoma of the adrenal gland. Indian J Pediatr 2004;71: 545–547.
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