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PEDIATRICS Vol. 113 No. 2 February 2004, pp. 412-415

EXPERIENCE AND REASON

Ipsilateral Hemangioma and Aortic Arch Anomalies in Posterior Fossa Malformations, Hemangiomas, Arterial Anomalies, Coarctation of the Aorta, and Cardiac Defects and Eye Abnormalities (PHACE) Anomaly: Report and Review

Gabriele Bronzetti, MD*, Alessandro Giardini, MD*, Annalisa Patrizi, MD{ddagger}, Daniela Prandstraller, MD*, Andrea Donti, MD*, Roberto Formigari, MD*, Marco Bonvicini, MD* and Fernando Maria Picchio, MD*

* Pediatric Cardiology
{ddagger} Institute of Dermatology, University of Bologna, Bologna, Italy


   ABSTRACT
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 ABSTRACT
CASE REPORTS
 DISCUSSION
 AMERICA'S SHAME
 REFERENCES
 
Posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta, and cardiac defects and eye abnormalities (PHACE) is a rare congenital anomaly with a broad spectrum of clinical manifestations with a striking female predominance. We describe an infant with PHACE anomaly and aortic coarctation who underwent cardiac catheterization to clearly define the complex anatomy of the aortic lesion before surgical repair. Review of the literature documents a highly significant association between ipsilateral hemangiomas and cerebrovascular and aortic arch anomalies. We conclude that cardiac catheterization is required to define the complex anatomy of aortic lesions and should be performed in all patients with PHACE and evident aortic involvement to plan appropriate and safe surgical repair.

Key Words: PHACE • aortic arch • hemangioma • aortic coarctation • cardiac catheterization

Abbreviations: PHACE, posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta, and cardiac defects and eye abnormalities

Infantile hemangiomas are common vascular lesions, occurring in 8% of all newborns, and are usually solitary (90%). However, segmental hemangiomas, which may occur in unusual locations in deep tissue, occur in several syndromes.1 Posterior fossa malformations, hemangiomas, arterial anomalies, coarctation of the aorta, and cardiac defects and eye abnormalities (PHACE) is an uncommon congenital neurocutaneous syndrome with a striking female predominance. Approximately 70% of affected infants have no more than 1 of the extracutaneous manifestations.2,3 Hemangiomas and cardiovascular malformations are seen also in supraumbilical midline raphe and midline defects.4–7 Several case reports exist of PHACE-associated cardiovascular anomalies, most often aortic coarctation or interruption.1–29 We describe a further case with PHACE syndrome with complex coarctation. A review of the reported cases of PHACE shows a highly significant prevalence of ipsilateral hemangiomas and aortic arch anomalies.


   CASE REPORTS
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A 2-month-old girl with an extensive, left facial hemangioma extending to the cheek, lips, and eye (Fig 1 a) was referred for suspected aortic coarctation. Echocardiography showed normal intracardiac anatomy with a persistent left superior vena cava draining into the coronary sinus. A suprasternal scan documented a complex aortic anomaly with severe narrowing of the posterior aspect of the aortic arch and absent antegrade flow at the level of the aortic isthmus. A color Doppler scan showed multiple collateral vessels running close to the aorta and evidence of periaortic extension of the hemangioma. Magnetic resonance imaging excluded gross intracranial anomalies but confirmed the extension of the hemangioma to the left orbit and the mediastinum with severe aortic coarctation (Fig 1 b). Cardiac catheterization demonstrated type A interruption of the left-sided aortic arch distal to the take-off of the left carotid artery followed by a tortuous and narrow (3-mm) tract of descending aorta, receiving its sole supply from the left vertebral artery (Fig 1 c). The same examination showed a distal take-off of the left subclavian artery with cranial-caudal flow toward the normal diaphragmatic aorta. The patient underwent successful repair with interposition of a patch of cryopreserved pericardium between the aortic arch and the diaphragmatic aorta, using the interrupted tract as the roof of the reconstructed aorta.


Figure 1
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  		Fig 1. a, Cutaneous extension at presentation of the hemangioma to the left side of the face of the patient reported herein. Angio-magnetic resonance imaging (b) and angiographic (c) views of the thoracic aorta show that the morphology of the aortic arch is complex with an interrupted aortic segment (arrows) followed by a long, tortuous pseudocoarctation. All these anomalies are also observable (d and e) in another patient with PHACE anomaly seen by us.8

 
A 40-day-old boy with a left-sided hemangioma extended to the face and neck was referred to us a few months later. In this patient, aortic angiography showed a looped left aortic arch with significant segmental narrowing of the descending thoracic aorta and with a stenotic and distally displaced origin of the left subclavian artery (Fig 1, d and e).


   DISCUSSION
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AMERICA'S SHAME
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A review documents that the clinical sequence described above is actually rather typical of other cases (n = 32) with cardiovascular involvement2–30 traced by us in the MEDLINE database (using PHACE, aorta, aortic coarctation, hemangioma, and hemangioma as abstract search terms; Table 1). In 13 cases there was a right aortic arch with coarctation or interruption, which is generally a rare finding.3–5,9–13,15,20,27 We considered the possibility that, as already suggested for epi-aortic vessel anomalies in patients with PHACE anomaly,3,22 an ipsilateral relationship might exist between the location of the hemangioma and the side of the aortic arch.


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  		TABLE 1. Presentation Characteristics of the 33 Reported Cases of PHACE Syndrome

 
Excluding the 4 cases with undescribed hemangioma location, we noticed that all reported cases (11 of 11) of right aortic arch also had a right hemangioma. Furthermore, a similar ipsilateral association was present in 22 of 23 (95%) patients with left aortic arch. Both of these associations are highly significant (Fisher’s exact test: P < .00001). Thus, a close association seems to exist between aortic arch (with/without coarctation) and hemangioma laterality. This observation lead us to hypothesize that a single genetic defect involved in lateralization may be responsible for the aortic arch defects, great artery anomalies, and facial hemangiomas found in patients with PHACE anomaly.

Hemangiomas associated with midline developmental defects (including sternal cleft and supraumbilical abdominal raphe) usually involve the face.12 Opitz31,32 postulated that sternal clefting and hemangiomas probably occur between 8 and 10 weeks of gestation via an abnormality in a developmental field. Field development is 1 of the phylogenetic consequences of regression of metamerism, with 6 pairs of arterial branches coming to form a single aortic arch system. This theory implies that certain insults of embryonic development at a specific critical time may give rise to very similar developmental outcomes, as in PHACE anomaly.31,32 The concept that a single defect may be responsible for the anomalies observed in PHACE could explain why some patients show cardiovascular defects only, without any intracranial and skeletal involvement, as observed in both of the patients seen by us and in other remarkably similar reported cases.3,8,15,27 Such cases confined to cardiovascular defects would seem to suggest that they may represent a partial expression of this defect rather than a separate clinical entity. This concept is reinforced by the many observations of patients with PHACE anomaly without any cardiovascular involvement.2,5,7,12,13,18,22

Other authors3,15 have also described highly complex aortic arch morphology similar to that observable in the 2 patients seen by us (Fig 1, d and e). This suggests that, in contrast to simple aortic coarctation or the type of aortic arch interruption observed in patients with DiGeorge syndrome, the aortic anomalies found in the context of PHACE may represent a distinctive morphologic entity with unusually complex and unpredictable anatomic involvement. In fact, both of the patients seen by us presented a long tract of markedly narrowed aorta (from the posterior arch to diaphragmatic aorta). Interestingly, in both the patients observed by us, histopathologic examination of the diseased aorta showed microstructural anomalies in the intimal and medial layers, possibly due to inflammation or dysplasia of the aortic wall. In our experience, patients’ referrals were due to clinical findings consistent with aortic coarctation (absent femoral pulses and precordial systolic murmur), which led us to perform transthoracic echocardiography. However, the echo scans, although suggesting an aortic anomaly, were unable to clearly define the complex aortic anatomy (ie, coarctation/interruption and blood supply to the descending thoracic aorta). On clinical grounds, these observations imply that routine transthoracic echocardiography33 cannot provide a complete preoperative functional and anatomic definition in patients with PHACE. We think that cardiac catheterization and angiography and/or magnetic resonance should be mandatory to plan safe, complete surgical repair of the aortic defect.


   AMERICA’S SHAME
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 ABSTRACT
 CASE REPORTS
 DISCUSSION
 AMERICA'S SHAME
REFERENCES
 
"There are approximately two million people in jail in America today, 2 166 260 at last count: more than four times as many people as thirty years ago. It is the largest number in our history. More than 500 in every 100 000 Americans are behind bars, between four and ten times the incarceration rate of any civilized country in the world ... But gross numbers are only part of the story. The other part is racial imbalance. Twelve percent of African-American men between twenty and thirty-four are currently behind bars (the highest figure ever recorded by the Justice Department) compared with 1.6% of white men of comparable ages. And according to the same source, 28% of black men will be sent to jail in their lifetimes."

Bruner JS. Do not pass go. New York Review of Books. September 25, 2003

Submitted by Student


   ACKNOWLEDGMENTS
 
We acknowledge Mr Robin M.T. Cooke for scientific editing and Ms Claudia Cavicchi for valuable help.


   FOOTNOTES
 
Received for publication May 29, 2003; Accepted Oct 29, 2003.

Reprint requests to (G.B.) Pediatric Cardiology and Adult Congenital Unit, University of Bologna, Policlinico S. Orsola-Malpighi, Via Massarenti 9, 40138 Bologna, Italy. E-mail: gabronz{at}hotmail.com


   REFERENCES
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 ABSTRACT
 CASE REPORTS
 DISCUSSION
 AMERICA'S SHAME
 REFERENCES
 

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PEDIATRICS (ISSN 1098-4275). ©2004 by the American Academy of Pediatrics

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