Infantile Orofacial Hemangioma With Ipsilateral Peripapillary Excavationin Girls: A Variant of the PHACE Syndrome

The PHACE syndrome is a neurocutaneous syndrome that includes the followingprimary features: posterior fossa malformations of the brain, large facialhemangiomas, arterial anomalies, cardiac anomalies and aortic coarctation,and eye abnormalities.^1,2 Itoccurs almost exclusively in girls. Several recent reports have documentedan association between orofacial hemangioma and excavated optic disc anomalies(morning glory disc anomaly and peripapillary staphyloma) in girls. Metryet al² recently proposed that this associationfalls within the spectrum of PHACE syndrome. We document ipsilateral intracranialvascular abnormalities in 2 girls with juvenile orofacial hemangioma and excavatedoptic discs to provide further evidence that these patients fall within thespectrum of PHACE syndrome.

A 6-year-old girl was referred for evaluation of unilaterally decreasedvision in the right eye. She was born full term, and her perinatal coursewas uneventful. At 2 weeks of age, she developed multiple hemangiomas involvingthe face, lip, parotid gland, and throat on the right side. At 1 month ofage, these hemangiomas began to grow rapidly (Figure 1A). Magnetic resonance imaging confirmed massive hemangiomatousinvolvement of the right parotid gland and right side of the face. Resultsof a cardiology evaluation with echocardiography were normal. The hemangiomascontinued to enlarge until the patient was 9 months of age. Treatment withoral steroids and multiple laser treatments to the gingival mucosa and theparotid gland produced regression of the tumor. At 1 year of age, she wasnoted to have an esotropia of the right eye.

Visual acuity was 20/160 OD and 20/20 OS. Both pupils reacted brisklyto light, and there was a mild right afferent pupillary defect. Extraocularmovements were full. Fixating near, she had 16 prism diopters of esotropiaand fixated eccentrically with the right eye. Results of slitlamp examinationwere normal. Cycloplegic refractive error was +2.00 OD and +2.75 OS. Retinalexamination disclosed a morning glory disc anomaly in the right eye with anelevated pigmented area of juxtapapillary scarring temporal to the disc (Figure 1B). Magnetic resonance angiographydemonstrated marked tortuosity of the supraclinoid right internal carotidartery and narrowing of the proximal right middle cerebral artery (Figure 1C).

A 6-week-old girl was evaluated for right-sided epiphora. Her perinatalcourse had been complicated by respiratory difficulties requiring temporaryresuscitation. External examination disclosed a large capillary hemangiomaon the right upper eyelid; tip of the nose; and right cheek, neck, and shoulder.In the ensuing weeks, the patient developed respiratory insufficiency requiringintubation. Results of a cardiology evaluation with echocardiography werenormal. Magnetic resonance imaging disclosed several large hemangiomas inthe chest, with extension to the upper aorta, displacement of the right upperlobe of the lung, and displacement of the trachea and larynx. The orofacialcomponent of the hemangioma involved the right masseter muscle, parotid gland,orbit, and soft tissues of the tongue and lips on the right side.

Ophthalmologic examination of the patient at age 6 months showed esotropiaand dense amblyopia of the right eye. A small conjunctival hemangioma waslocalized to the 3-o'clock position, the pupil was slightly eccentric, theiris stroma was moderately atrophic, and a persistent pupillary membrane wasnoted. Retinal examination showed excavation of the peripapillary retina.

She was treated with oral steroids and interferon, and the hemangiomaregressed during the next 2 years. At 7 years of age, however, orofacial remnantsof the hemangioma were still evident (Figure2A). Visual acuity was 20/80 OD and 20/20 OS. Cycloplegic refractionwas –11.75 +2.00 ×95° OD and +3.00 +1.50 ×110° OS.Retinal examination disclosed a large peripapillary staphyloma in the righteye, which enclosed a normal-appearing optic disc (Figure 2B). The macula was situated at the border of the staphyloma.Examination of the left optic disc and retina disclosed no abnormalities.Magnetic resonance angiography disclosed a developmental vascular anomalyof the origin of the right ophthalmic artery (Figure 2C).

In 1998, Holmstrom and Taylor³ describedan association of facial capillary hemangioma with morning glory disc anomalyin 3 girls. Kirath et al⁴ subsequentlyreported peripapillary staphyloma in a girl with a large ipsilateral orofacialhemangioma. Our 2 cases demonstrate that these findings may also be associatedwith ipsilateral cerebral vascular dysgenesis.

The relationship between large facial hemangiomas and cerebrovascularand facial arterial anomalies was recognized by Pascual-Castroviejo⁵ in 1978. Although cardiac and cerebellar malformationsare usually present, it is now believed that PHACE syndrome represents a spectrumof anomalies (Table 1) that varyconsiderably from one case to another. In 70% of reported cases, only 1 extracutaneousmanifestation of the syndrome has been present, with extracutaneous manifestationsbiased toward the specialty for which the article was written.²

The orofacial hemangiomas seen in PHACE syndrome are characteristicallylarge, segmental, and plaquelike.^1,2 Thepathogenesis of PHACE syndrome is unknown. The clinical manifestations ofPHACE syndrome conform to a developmental field defect, which results fromerrors within morphoregulatory genes that determine a constellation of developmentalanomalies in a spatially coordinated, temporally synchronous manner.^2,6 Its confinement to girls raisesthe possibility of an X-linked lethal mutation.² Toour knowledge, no familial cases of PHACE syndrome have been reported.

Other clinical features of PHACE syndrome are in Table 1.² The most common centralnervous system abnormalities have involved the posterior fossa, most notablythe Dandy-Walker malformation, characterized by a hypoplastic or absent cerebellarvermis and a posterior fossa cyst continuous with the fourth ventricle.^1,7

Cerebellar atrophy and arachnoid cyst with cerebellar hypoplasia havealso been reported, as have frequent alterations in the intracranial carotidvasculature.^1,8 Pascual-Castroviejo,⁷ who routinely performs carotid angiography inchildren with large facial hemangiomas, reports frequent alterations of theintracranial vasculature, particularly the carotid artery. Burrows et al⁹ reported cerebral infarction secondary to progressiveocclusive arterial disease in 4 infants who were previously healthy. In additionto a variety of structural cardiac abnormalities and aortic coarctation, ventraldevelopmental defects such as sternal pits, sternal clefting, and supra-abdominalraphe should be sought.^1,2

Metry et al² considered the co-occurrenceof morning glory disc anomaly and ipsilateral facial hemangioma as fallingwithin the spectrum of PHACE syndrome. The ipsilateral neurovascular abnormalitiesin the territory of the carotid circulation in our 2 cases supports this contention.The association of a unilateral morning glory disc anomaly or peripapillarystaphyloma with ipsilateral facial hemangioma mandates a careful search forassociated cardiac, aortic, and cerebrovascular anomalies.

This study was supported in part by a grant from Research to PreventBlindness Inc, New York, NY.

Corresponding author: Michael C. Brodsky, MD, Ophthalmology and Pediatrics,Arkansas Children's Hospital, 800 Marshall St, Little Rock, AR 72202-3591(e-mail: brodskymichaelc@uams.edu)