PHACE Syndrome

December 1, 2007

An otherwise healthy female infant presented at birth with a lesion on the left side of the face that involved the frontotemporal scalp, periocular area, nose, and upper lip (A). She was born at term via spontaneous vaginal delivery after an uncomplicated gestation. The initial clinical impression was that of a port-wine stain associated with Sturge-Weber syndrome.

An otherwise healthy female infant presented at birth with a lesion on the left side of the face that involved the frontotemporal scalp, periocular area, nose, and upper lip (A). She was born at term via spontaneous vaginal delivery after an uncomplicated gestation. The initial clinical impression was that of a port-wine stain associated with Sturge-Weber syndrome.

Magnetic resonance angiography of the brain revealed a large capillary hemangioma that extended into the scalp, face, maxilla, and parotid region. The left A1 segment of the anterior cerebral artery was absent and the right external maxillary artery was enlarged and crossed to feed the hemangioma on the left. MRI scans showed no evidence of calcifications.

Echocardiography showed a normal aorta with a left-sided aortic arch and no coarctation. An ophthalmological evaluation revealed healthy optic nerves and no evidence of glaucoma.

These findings suggested PHACE syndrome, which consists of:

Posterior cranial fossa malformations, including Dandy-Walker syndrome (hypoplasia or agenesis of the cerebrum), corpus callosum, and other structural brain anomalies.

Hemangiomas.

Arterial anomalies.

Cardiovascular disorders, including aortic coarctation, aortic aneurysms, and other structural cardiac defects.

Eye disorders, such as microphthalmos, retinal vascular abnormalities, cataracts, optic atrophy, and other structural ocular lesions.1

Infants with this neurocutaneous syndrome have extensive hemangiomas most commonly on the face and 1 or more of the congenital anomalies listed above. The presence of ventral development defects (eg, sternal clefting and supraumbilical raphe) is referred to as PHACES syndrome. With the wide spectrum of anomalies, there is a range of clinical presentations and many partial phenotypes. Although the pathogenesis is not well understood, neural crest involvement and an X-linked dominant mode (because 90% of cases involve female infants) have been suggested.2

Because hemangiomas are the most common nonmalignant vascular tumors in infancy, they may not be associated with conditions such as PHACE syndrome. The facial hemangiomas in patients with PHACE syndrome usually grow in an aggressive pattern, as was the case in this infant shown here at age 18 months (B).3 Patients with large facial hemangiomas should be screened for PHACE syndrome with MRI of the brain, and by ophthalmological examination, echocardiography, and frequent neurological and head circumference examinations.

Early diagnosis and management by a multidisciplinary team is imperative to decrease the number and severity of the complications--especially cardiac and neurological sequelae. PHACE syndrome is associated with progressive vasculop- athies that can lead to seizure or acute arterial ischemic stroke.4

Treatment is reserved for hemangiomas that are considered life- or function-threatening and depends on the subtype and size of the lesion. Oral corticosteroids are first-line therapy. Intralesional and topical corticosteroids may be effective for localized lesions. Administration of live-virus vaccines should be deferred for at least 4 weeks after therapy. Other treatment modalities include pulsed dye laser, which is useful for ulcerated hemangiomas, and interferon alfa 2a or 2b, which may be used for refractory hemangiomas. However, the latter therapy is limited because of the significant potential for neurological complications.2

In this patient, a course of oral corticosteroids resulted in little improvement. She subsequently underwent several rounds of pulsed dye laser therapy and surgical debulking, which dramatically reduced the size of the lesion. *

References:

REFERENCES:

1.

Paller AS, Mancini AJ.

Hurwitz's Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence.

3rd ed. Philadelphia: Elsevier Saunders; 2006:316-317.

2.

Haggstrom AN, Lammer EJ, Schneider RA, et al. Patterns of infantile hemangiomas: new clues to hemangioma pathogenesis and embryonic facial development.

Pediatrics.

2006;117:698-703.

3.

Poetke M, Frommeld T, Berlien HP. PHACE syndrome: new views on diagnostic criteria.

Eur J Pediatr Surg.

2002;12:366-374.

4.

Metry DW. A newborn girl with large red plaque on her face.

Pediatr Ann.

2006;35:423-426.