4 June 2008
PHACE SYNDROME: A CONSTELLATION OF CEREBRAL AND CARDIOVASCULAR ANOMALIES AND SEGMENTAL HAEMANGIOMAS
PHACE syndrome is an uncommon neurocutaneous syndrome that manifests with multi-system involvement. It refers to the association of large, plaque-like, ‘segmental’ haemangiomas of the face, posterior fossa brain malformations, arterial cerebrovascular anomalies, cardiovascular anomalies, eye anomalies and ventral developmental defects.1 This letter describes a male baby who was born to a 41-year-old mother by elective section at term gestation and who weighed 2.88 kg. A prenatal diagnosis of posterior fossa malformation had been made at a 19-week anomaly scan.
The infant was delivered breech by LSCS with forceps lift-out and was noted to have extensive bruising on left side of the face with an ipsilateral facial palsy. Over the next week the bruising was replaced by fine telangiectasia, which became darker and evolved into a confluent segmental facial haemangioma in the distribution of trigeminal cranial nerve extending into the oral cavity (Fig. 1). The important differential diagnosis at this stage was Sturge-Weber syndrome.
MRI brain was consistent with Dandy Walker malformation. In addition, a soft tissue mass encircling cranial nerves VI and VII (possible acoustic neuroma, Fig. 2) along with hypoplasia of left vertebral artery was noted. The facial haemangioma was seen to extend internally to the left cavernous sinus, the extraconal spaces of the left eye and the superior mediastinum. While carotid Doppler showed no evidence of stenosis, the echocardiogram showed features consistent with coarctation of aorta. The ophthalmology review was unremarkable, showing no evidence of raised intraocular pressure or retinal detachment/optic neuropathy. He was started on laser therapy for the surface hemangioma after which it showed signs of gradual resolution. He was readmitted at 8 weeks of age with stridor and bronchoscopy revealed a large sub-glottic haemangioma obstructing most of the airway, which was managed by placement of a tracheostomy tube.
While the acronym PHACE (OMIM 606519) was suggested by Frieden in 1995,2 the exact incidence of PHACE syndrome is unknown. Pathogenesis too is unknown, while the constellation of anomalies generally represents a ‘developmental field defect’, whereby an insult in embryogenesis at a critical time gives rise to similar developmental outcomes.3 The timing of these errors in morphogenesis occurs early, probably between 3 and 12 weeks of gestation, prior to or during early vasculogenesis. The syndrome represents a spectrum of disease, with few infants manifesting the entire constellation of anomalies, some components appearing later. The marked female preponderance (>80%) suggests a possibility of X-linked inheritance with lethality in males.1 Both sporadic and X-linked or autosomal inheritance patterns are reported, the X-linked form being typically bilateral and diffuse, and often associated with a mutation of filament A gene (FLNA) on Xq28.4 The hallmark of PHACE syndrome, a large, segmental facial haemangioma, may involve one to several facial dermatomes, and an early presentation may be mistaken for the port wine stain associated with the Sturge-Weber syndrome.
Structural and cerebrovascular brain malformations occur in at least half. Posterior fossa malformations, including the Dandy-Walker complex, are the most common, and others include agenesis of corpus callosum and polymicrogyria. Developmental delay is a common association. Cerebrovascular defects present primarily as carotid artery anomalies, but also include aberrant/anomalous origins and aneurysm of cerebral vessels. The cerebrovascular anomalies, especially carotid artery anomalies, are of particular concern because of predisposition to progressive arterial occlusion and stroke.5,6 Cardiac anomalies include coarctation of the aorta and septal defects, while ophthalmologic anomalies include retinal vascular abnormalities, optic nerve atrophy, and colobomas, among others. Infants with PHACE syndrome could represent up to 20% of infants with segmental facial hemangiomas, and both progressive and regressive vascular phenomena may occur in this syndrome.1 The most common therapeutic option directed at regression of haemangioma is prednisolone/ methylprednisolone, while others include topical steroids, pulsed dye laser, interferon alpha, vincristine, excision surgery and wound care.1
To summarise, a segmental hemangioma may be an initial presentation of PHACE syndrome, and a high index of suspicion and thorough investigation would optimise management.