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Pediatric Pulmonology 41:592–596 (2006) CASE REPORT Horseshoe Lung and Facio-Auriculo-Vertebral Sequence: A Previously Unreported Association Lisa D’Alessandro, MD, 1 Tom Kovesi, MD, 2 * Sherief Massoud, MD, 3 Jane Lougheed, MD, 2 Alasdair Hunter, MD, 2,4 and Joseph Reisman, MD 2 Summary. We describe a case of horseshoe lung in an infant with facio-auriculo-vertebral (FAV) sequence that included mild hemifacial microsomia, ear anomalies, a missing left rib, left hemivertebrae (T2–T4), and complex congenital heart disease. Of the approximately 40 cases of horseshoe lung described since 1962, most are reported in association with scimitar syndrome, and only four reported cases were associated with left lung hypoplasia. None of these cases included malformations consistent with a diagnosis of FAV sequence. Pediatr Pulmonol. 2006; 41:592–596. ß 2006 Wiley-Liss, Inc. Key words: Goldenhar syndrome; respiratory system abnormalities; cardiovascular abnormality. INTRODUCTION Goldenhar sequence (oculoauriculovertebral dysplasia) was reported as early as the 1860s, and was described by Gorlin et al. in 1963 as including ocular and ear malformations, and vertebral defects. 1,2 Over time, it has become apparent that Goldenhar syndrome is part of a broader and heterogeneous spectrum of congenital ano- malies, variously referred to as hemifacial microsomia, facio-auriculo-vertebral (FAV), sequence, and oculoaur- iculovertebral spectrum, all of which are included under 164210 in the Online Mendelian Inheritance in Man. 3 Pulmonary malformations, consisting primarily of pul- monary hypoplasia, appear to be relatively common in affected patients. Horseshoe lung is a rare congenital malformation in which the lungs are connected by an isthmus of lung parenchyma posterior to the pericardium. We describe the first reported case of horseshoe lung in association with FAV sequence. CASE REPORT Pregnancy and Birth History The subject was female, and the second of monochor- ionic twins born to a 27-year-old gravida 4, abortus 3 (G 4 A 3 ) mother. The twin was unaffected. The mother reported taking levothyroxine for hypothyroidism throughout the pregnancy, but denied tobacco, alcohol, and drug use. She had recurrent genital herpes, and was treated with acyclovir 2 days prior to delivery. She was rubella-immune, and hepatitis B- and HIV-negative. Complex congenital cardiac malformations were identi- fied prenatally by ultrasound. The infant was born by cesarean section at 37 weeks of gestation, and weighed 2,314 g. She cried at birth, and her Apgars were 5 and 9 at 1 and 5 min. She was given brief positive-pressure ventilation and free-flow oxygen because of bradycardia 1 Department of Pediatrics, Children’s Hospital of Western Ontario, London, Ontario, Canada. 2 Department of Pediatrics, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada. 3 Department of Radiology, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada. 4 Department of Genetics, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada. *Correspondence to: Tom Kovesi, Department of Pediatrics, Children’s Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON Canada, K1H 8L1. E-mail: [email protected] Received 1 September 2005; Revised 8 December 2005; Accepted 11 December 2005. DOI 10.1002/ppul.20404 Published online 14 April 2006 in Wiley InterScience (www.interscience.wiley.com). ß 2006 Wiley-Liss, Inc.

Horseshoe lung and facio-auriculo-vertebral sequence: A previously unreported association

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Pediatric Pulmonology 41:592–596 (2006)

CASE REPORT

Horseshoe Lung and Facio-Auriculo-VertebralSequence: A Previously Unreported Association

Lisa D’Alessandro, MD,1 Tom Kovesi, MD,2* Sherief Massoud, MD,3 Jane Lougheed, MD,2

Alasdair Hunter, MD,2,4 and Joseph Reisman, MD2

Summary. We describe a case of horseshoe lung in an infant with facio-auriculo-vertebral (FAV)

sequence that included mild hemifacial microsomia, ear anomalies, a missing left rib, left

hemivertebrae (T2–T4), and complex congenital heart disease. Of the approximately 40 cases of

horseshoe lung described since 1962, most are reported in association with scimitar syndrome,

and only four reported cases were associated with left lung hypoplasia. None of these cases

included malformations consistent with a diagnosis of FAV sequence. Pediatr Pulmonol. 2006;

41:592–596. � 2006 Wiley-Liss, Inc.

Key words: Goldenhar syndrome; respiratory system abnormalities; cardiovascular

abnormality.

INTRODUCTION

Goldenhar sequence (oculoauriculovertebral dysplasia)was reported as early as the 1860s, and was described byGorlin et al. in 1963 as including ocular and earmalformations, and vertebral defects.1,2 Over time, it hasbecome apparent that Goldenhar syndrome is part of abroader and heterogeneous spectrum of congenital ano-malies, variously referred to as hemifacial microsomia,facio-auriculo-vertebral (FAV), sequence, and oculoaur-iculovertebral spectrum, all of which are included under164210 in the Online Mendelian Inheritance in Man.3

Pulmonary malformations, consisting primarily of pul-monary hypoplasia, appear to be relatively common inaffected patients. Horseshoe lung is a rare congenitalmalformation in which the lungs are connected by anisthmus of lung parenchyma posterior to the pericardium.We describe the first reported case of horseshoe lung inassociation with FAV sequence.

CASE REPORT

Pregnancy and Birth History

The subject was female, and the second of monochor-ionic twins born to a 27-year-old gravida 4, abortus 3(G4A3) mother. The twin was unaffected. The motherreported taking levothyroxine for hypothyroidismthroughout the pregnancy, but denied tobacco, alcohol,and drug use. She had recurrent genital herpes, and was

treated with acyclovir 2 days prior to delivery. She wasrubella-immune, and hepatitis B- and HIV-negative.Complex congenital cardiac malformations were identi-fied prenatally by ultrasound. The infant was born bycesarean section at 37 weeks of gestation, and weighed2,314 g. She cried at birth, and her Apgars were 5 and 9 at1 and 5 min. She was given brief positive-pressureventilation and free-flow oxygen because of bradycardia

1Department of Pediatrics, Children’s Hospital of Western Ontario,

London, Ontario, Canada.

2Department of Pediatrics, Children’s Hospital of Eastern Ontario,

University of Ottawa, Ottawa, Ontario, Canada.

3Department of Radiology, Children’s Hospital of Eastern Ontario,

University of Ottawa, Ottawa, Ontario, Canada.

4Department of Genetics, Children’s Hospital of Eastern Ontario,

University of Ottawa, Ottawa, Ontario, Canada.

*Correspondence to: Tom Kovesi, Department of Pediatrics, Children’s

Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON Canada,

K1H 8L1. E-mail: [email protected]

Received 1 September 2005; Revised 8 December 2005; Accepted 11

December 2005.

DOI 10.1002/ppul.20404

Published online 14 April 2006 in Wiley InterScience

(www.interscience.wiley.com).

� 2006 Wiley-Liss, Inc.

and poor oxygen saturation, andwas placed on continuouspositive airway pressure. A prostaglandin E infusion wasstarted, and she was transferred to the Neonatal IntensiveCare Unit (NICU) at the Children’s Hospital of EasternOntario (CHEO). Physical examination revealed a two-vessel cord. She had skin tags on the left cheek and justanterior to the left tragus, and an overfolded left helix.Therewas mild hypoplasia of the left lower face. The eyeswere normal without choristoma, and no abnormalities ofthe extremities were apparent.

Investigations in the NICU

An admission chest x-ray revealed an opacified lefthemithorax obscuring the left heart border, and a normalright lung (Fig. 1). Therewere segmentation abnormalitiesin the upper thoracic spine, with hemivertebrae from T2–T4, and an associated scoliosis convex to the right, and theleft first rib was absent. An echocardiogram revealedlevocardia, a double-outlet right ventricle, a hypoplasticleft ventricle, and mitral valve atresia. The great arteriesarose side-by-side, with a normal aortic valve and mildpulmonary valve stenosis. The left pulmonary artery wasabsent, and there was a large patent ductus arteriosus andnormal-sized right pulmonary artery. The right pulmonaryveins drained normally, but the left pulmonary veinsappeared small. There was a right aortic arch with aretroesophageal aberrant left subclavian artery.

A computerized tomographic (CT) scan of the chestshowed that the mediastinal structures were shiftedslightly to the left. A small left main-stem bronchus wasobserved, and a band of lung tissue with associated bloodvessels was seen crossing from right to left behind the

heart, which is consistent with horseshoe lung. A pleuralreflection in the midanterior portion of the medial side ofthe right lungwas suggestive of an accessory azygous lobe(Fig. 2).A head ultrasound was normal except for a mildly

dilated left lateral ventricle. An abdominal ultrasounddemonstrated normal liver, spleen, and kidneys. Hearingwas assessed as normal.A medical genetics consultation concluded that the

mild left facial microsomia, skin tags, complex congenitalheart disease, missing left rib and left hemivertebrae,and pulmonary malformations were consistent with adiagnosis of FAV sequence. Shewas discharged at 14 daysof age.

Subsequent Course

The patient was admitted at 5.5 weeks of age withcongestive heart failure. She underwent cardiac catheter-ization, followed by main pulmonary artery banding. Herrecovery was complicated by multiple episodes of apneaand bradycardia that required cardiopulmonary resuscita-tion, intubation, and ventilation. A magnetic resonancescan (MRI) of the brain revealed no abnormality apartfrom a thin but intact corpus callosum. An MRI of theheart showed no evidence of a vascular ring, and a secondMRI of the chest (Figs. 3, 4) revealed an inferior vena cavainterrupted in the porta hepatis below the diaphragm, andone hepatic vein draining directly into the right atrium.Bronchoscopy demonstrated that a tracheal bronchus waspresent, and the left main-stem bronchus was hypoplasticwith no visible branches, although it was difficult to enterthis bronchus. Gastroesophageal reflux was diagnosed on

Fig. 1. Chest radiograph. Antero-posterior view of chest shows

left hemithorax to be almost completely opacified, obscuring

heart outline. Right lung is well-aerated and is clear. There are

segmentation abnormalities of upper thoracic spine, with right

convex scoliosis.

Fig. 2. Computerized tomographic (CT) scan of lungs. Axial CT

cut of thorax demonstrates a band of lung with vessels crossing

from right side to left side of chest (arrow) On other views (not

included), right pulmonary artery was identified, but left

pulmonary artery could not be demonstrated.

Horseshoe Lung and FAV Sequence 593

the basis of an abnormal pH probe study. Physiotherapywas prescribed for torticollis. The karyotype was 46,XX.The patientwas subsequently readmitted to hospital at 4

months of age with an acute respiratory infection due toinfluenza A, a right upper lobe collapse, and feedingdifficulties. A repeat bronchoscopy confirmed the earlierfindings, and also demonstrated tracheomalacia with abulging posterior membranous portion of the trachea, andpulsatile compression of the anterior trachea. Malacia of

the right middle and lower lobe bronchi were alsoobserved.

DISCUSSION

Facio-auriculo-vertebral sequence is an asymmetricdisorder of first and second branchial arch developmentthat has an increased rate of concurrent vertebral, cardiac(14–47%), and tracheoesophageal anomalies.2 The bran-chial arch anomalies include variable microtia, preauri-cular tags and fistulae, hypoplasia of the lower face, andunilateral macrostomia. The subgroup of patients withchoritomas are considered to have Goldenhar sequence(oculoauriculovertebral dysplasia). FAV sequence isconsidered to be a causally heterogeneous sequence ofbirth defects. In a thorough review of cases of lungagenesis and ipsilateral malformations, Cunningham andMann hypothesized that a disruption in dorsal aortic archbloodflow inweek 4 of gestation (a stagewhen the embryohas paired aortic arches) could selectively interfere withthe development of the lung, limbs, and derivatives of thefirst and second branchial arches, leading to a patternof ipsilateral malformations.4 A vascular cause for thedisruption of asymmetry in FAV has been suggestedrepeatedly in the literature.2,5,6 The finding of a greater-than-expected rate of some of the component anomalies ofFAV among relatives of patients with FAV sequencesuggests there may be a genetic contribution to itsetiology, and it was suggested that there may be geneticfactors involved in the vascular pathogenesis.7,8 A numberof patients have had chromosomal aberrations, but noconsistent karyotypic anomaly has been found.3 Disrup-tion of blastogenesis during weeks 1–4 of gestation, whenasymmetric development begins, is another commonlycited etiology, especially considering the many cases ofdiscordant Goldenhar syndrome among monozygotictwins.5,6 Recent systematic analysis showed a relationshipbetween the anomalies seen in FAV and those of thevertebral anomalies, anal atresia, tracheo-esophagealfistula, and renal anomalies (VATER) association.9 Thereis some evidence to suggest that disorders which ariseduring blastogenesis, including FAV sequence, VAC-TERL, and caudal regression syndrome, should beclassified under the axial mesodermal dysplasia spectrumof disorders, as many cases were reported which overlapdiagnostic criteria.10–12 It was proposed that abnormal-ities in cells migrating from the primitive streak couldresult inmultiple abnormalities ofmesodermal derivativesalong the length of the embryo.13

Pierpont et al. reviewed 45 cases of oculoauriculover-tebral dysplasia, and found 8 cases with pulmonarymalformations.2 All 8 cases also had cardiac anomalies.Five patients had right lung malformations, includinghypoplasia and incomplete lobulation of the right lung.Two patients had left lungmalformations: one had aplasia,

Fig. 4. Magnetic resonance imaging scan of thorax. Coronal

image of thorax shows horseshoe lung. Black, vertical esopha-

gus is apparent in left hemithorax (arrow).

Fig. 3. Magnetic resonance imaging scan of thorax. Axial image

of thorax shows main pulmonary artery (black arrow), and

elongated right pulmonary artery (white arrow) with no left

pulmonary artery demonstrated. Horseshoe lung at base of

left hemithorax is identified (grey arrow). On other views

(not included), right main-stem bronchus is elongated, and left

main-stem bronchus is hypoplastic. Esophagus is anterior and is

displaced to left. Right pulmonary vein was identified, but no left

pulmonary vein could be identified.

594 D’Alessandro et al.

and the other had hypoplasia. One patient had bilateralunillobed lungs. Pierpont et al. also remarked on anassociation between the laterality of the pulmonarymalformation and the eye and ear malformations.2

Downing and Kilbride reported on a case of Goldenharsyndrome with left-sided malformations (hemifacialmicrosomia, bilateral epibulbar dermoids, and absenceof the left ear canal) along with tracheal stenosis,tracheoesophageal cleft, and left pulmonary agenesis.14

These cases are consistent with our case, in which the leftlung was aplastic or hypoplastic (see below) and the earabnormalities were left-sided, and there was also anipslateral missing rib. Our case of FAV sequence is uniquedue to the presence of a horseshoe lung.

In our patient, horseshoe lung was diagnosed by CTscan when a band of lung tissue with a vessel was seencrossing from right to left behind the heart. Horseshoelung is a rare congenital malformation in which the leftand right lungs are connected by an isthmus of lungparenchyma.15 It is most commonly associated with right-sided lung hypoplasia and scimitar syndrome. Approxi-mately 40 cases have been described since its initialdescription in the literature in 1962.16 Dupuis et al.reported 6 cases of horseshoe lung in 1994, along with acomprehensive review of the 30 cases previously reported(including one diagnosed in utero).16 Of the 35 live-borncases reviewed, 30 were associated with scimitarsyndrome (85%). Of the five live-born cases reported thatwere not associated with scimitar syndrome, two hadright hypoplasia, two had left hypoplasia, and one hadno lung hypoplasia. None of those five cases wereconsistent with the spectrum of malformations in FAVsequence.17–21 However, several of the anomaliesdescribed are consistent with our case, including adouble-outlet right ventricle and hypoplastic left heart,hypoplastic umbilical artery, and a butterfly thoracicvertebra and cervical hemivertebrae.19,20 None of the fourpreviously reported cases of horseshoe lung with left lunghypoplasia had malformations consistent with a diagnosisof FAV sequence.17,20,22,23

The development of horseshoe lung and other horse-shoe organs is thought to be associated with the inappro-priate fusion of splanchicmesoderm, potentially secondaryto deficiency of a mesodermal organizer.18,20,22 Pulmonaryagenesis is thought to be related to a vascular disruption,and Cunningham and Mann hypothesized that pulmonaryagenesis could lead to ipsilateral vessel maldevelopmentand subsequent structural malformations.4 Horseshoe lungcan be clearly differentiated fromother conditions inwhichbronchi or pulmonary vessesl cross the midline.15 In thepulmonary sling anomaly, a branch from one of the twomains-stem pulmonary arteries crosses the midline, tosupply blood to lung tissue of the opposite lung. In abridging bronchus, one lung lobe is supplied by a bronchusoriginating from the opposite main-stem with no interven-

ing lung tissue, and there is often an associated pulmonarysling.24 Braided bronchus was described by Wheeler et al.as an abnormal right main-stem bronchus with fourbranches, one forming a bridging bronchus to supply anaccessory lobe posterior to the heart, and three overlappingto form a braided structure.25 In our patient, magneticresonance reconstructions confirmed the presence of lungtissue in the left hemithorax, but the available endoscopicand radiologic investigations did not allow us to determinewhether this tissue is a hypoplastic left lung aerated via left-sided bronchi, horseshoe lung tissue expanding to occupythe lower left hemithorax, or a left-sided sequestrationcommunicating with the right lung via a right lower lobebronchus and blood vessels that communicate with theright lower lobe.15 However, regardless of the origin of theleft basal lung tissue, the crossover bronchus had interven-ing lung tissue, and therefore our patient did not have abridging bronchus. Furthermore, Hawass et al. stated thatin cases of bridging bronchus and accessory lung, anaerated isthmuswill not be apparent onCTimaging, andwetherefore conclude that our patient’s pulmonarymalforma-tion was a horseshoe lung.15

Our case of horseshoe lung in association with left lunghypoplasia and left-sided FAV sequence anomalies maybe either another variation of the spectrum of pulmonarymalformations, or possibly an example of horseshoe lungand FAV sequence arising as a result of the samedisruption in development. We suggest that horseshoelung should be considered among the list of congenitallung anomalies associated with FAV sequence. In ourpatient, the pattern of thoracic anomalies, with likelyhypoplasia of the left lung and other ipsilateral malforma-tions, is consistent with ipsilateral pulmonary and facialmalformations reported previously in this sequence.2

REFERENCES

1. Gorlin RJ, Jue KL, Jacobsen V, Goldschmidt E. Oculoauriculo-

vertebral dysplasia. J Pediatr 1963;63:991–999.

2. Pierpont MEM, Moller JH, Gorlin RJ, Edwards JE. Congenital

cardiac, pulmonary, and vascular malformation in oculoauricu-

lovertebral dysplasia. Pediatr Cardiol 1982;2:297–302.

3. McKusik VA. Hemifacial microsomia; HFM [monograph on the

Internet]. Baltimore: Online Mendelian Inheritance in Man. June

2005 [cited November 5, 2005]. Available from: http://www.

ncbi.nlm.nih.gov/entrez/dispomin.cgi?id¼164210

4. Cunningham ML, Mann N. Pulmonary agenesis: a predictor of

ipsilateral malformations. Am J Med Genet 1997;70:391–398.

5. Kumar A, Friedman JM, Taylor GP, Patterson MWH. Pattern of

cardiac malformations in oculoauriculovertebral spectrum. Am J

Med Genet 1993;46:423–426.

6. Lin HJ, Owens TR, Sinow RM, Fu PC Jr, DeVito A, Beall MH,

Lachman RS. Anomalous inferior and superior venae cavae with

oculoauriculovertebral defect: review of Goldenhar complex and

malformations of left-right asymmetry. Am J Med Genet 1998;

75:88–94.

7. Kaye CI, Martin AO, Rollnick BR, Nagatoshi K, Israel J,

Hermanoff M, Tropea B, Richtsmeier JT, Morton NE. Oculoaur-

Horseshoe Lung and FAV Sequence 595

iculovertebral anomaly: segregation analysis. Am J Med Genet

1992;43:913–917.

8. Soltan HC, Holmes LB. Familial occurrence of malformations

possibly attributable to vascular abnormalities. J Pediatr 1986;

108:112–114.

9. Kallen K, Robert E, Castilla EE, Mastroiacovo P, Kallen B.

Relation between oculo-auriculo-vertebral (OAV) dysplasia

and three other non-random associations of malformations

(VATER, CHARGE, and OEIS). Am J Med Genet 2004;127:

26–34.

10. Bergmann C, Zerres K, Peschgens T, Senderek J, Hornchen H,

Rudnik-Schoneborn S. Overlap between VACTERL and hemi-

facial microsomia illustrating a spectrum of malformations seen

in axial mesodermal dysplasia complex (AMDC). Am J Med

Genet 2003;121:151–155.

11. Russell LJ, Weaver DD, Bull MJ. The axial mesodermal dysplasia

spectrum. Pediatrics 1981;67:176–182.

12. Stewart JF, Nevin NC, Brown S. Axial mesodermal dysplasia

spectrum. Am J Med Genet 1993;45:426–429.

13. Wulfsberg EA, Grigbsy TM. Rokitansky sequence in association

with the facio-auriculo-vertebral sequence: part of a mesodermal

malformation spectrum? Am J Med Genet 1990;37:100–102.

14. Downing GJ, Kilbride H. An interesting case presentation:

pulmonary malformations associated with oculoauriculovertebral

dysplasia (Goldenhar anomalad). J Perinatol 1991;11:190–192.

15. Hawass ND, Badawi MG, Al-Muzrakchi AM, Al-Sammarai

AI, Jawad JA, Abdullah MA, Bahadim H. Horseshoe

lung: differential diagnosis. Pediatr Pulmonol 1990;20:580–584.

16. Dupuis C, Remy J, Remy-Jardin M, Coulomb M, Breviere GM,

Ben Laden S. The ‘‘horseshoe’’ lung: six new cases. Pediatr

Pulmonol 1994;17:124–130.

17. Purcaro A, Caruso L, Ciampani N, Inglese L. Polmone a ferro

di cavallo, malposizione cardiaca ed anomalie vascolari polmo-

nari: una syndrome caratteristica. G Ital Cardiol 1976;6:312–

316.

18. Cipriano P, Sweeney LJ, Hutchins GM, Rosenquist GC. Horse-

shoe lung in an infant with recurrent pulmonary infections. Am J

Dis Child 1975;128:1343–1345.

19. Freedom RM, Burrows PE, Moes CAF. ‘‘Horseshoe’’ lung: report

of five new cases. AJR 1986;146:211–215.

20. Hawass ND, Badawi MG, Fatani JA, Meshari AA, Edrees YB.

Horseshoe lung with multiple congenital anomalies. Acta Radiol

(Stockh) 1987;28:751–755.

21. Currarino G,Williams B. Causes of congenital unilateral pulmonary

hypoplasia: a study of 33 cases. Pediatr Radiol 1985;15:15–24.

22. Ersoz A, Soncul H, Gokgoz L, Kalaycioglu S, Tunaoglu S,

Kaptanoglu M, Yener A. Horseshoe lung with left lung hypo-

plasia. Thorax 1992;47:205–206.

23. Lutterman J, Jedeikin R, Cleveland DC. Horseshoe lung with left

lung hypoplasia and critical pulmonary venous stenosis. Ann

Thorac Surg 2004;77:1085–1087.

24. Rishavy TJ, Goretsky MJ, Langenburg SE, Klein MD. Anterior

bridging bronchus. Pediatr Pulmonol 2003;35:70–72.

25. Wheeler DS, Poss WB, Cocalis M, Krumwiede G, Gaston B.

Braided-bronchus: a previously undescribed airway anomaly.

Pediatr Pulmonol 1998;25:348–351.

596 D’Alessandro et al.