Posterior fossa malformations, hemangiomas, arterial anomalies, cardiac anomalies, and eye abnormalities (PHACE) syndrome is a rare condition characterized by multiple manifestations, including posterior fossa malformations (most commonly Dandy–Walker malformations), hemangiomas, arterial anomalies, coarctation of the aorta and other cardiac defects, and eye abnormalities. Hemangiomas (including the eyelid, ptosis, and microphthalmia) are the most common findings in patients with PHACE syndrome, followed by cataracts, Horner's syndrome, iris vessel hypertrophy, iris hypoplasia, sclerocornea, lens coloboma, optic nerve atrophy and retinal vascular abnormality, choroidal hemangiomas, congenital fourth nerve palsy, exophthalmos, strabismus, morning glory deformity, and peripapillary staphyloma, which were reported as single case reports.1,2 Ocular findings are primarily ipsilateral to the hemangioma, and are seen in 19% to 26% of cases with PHACE syndrome.1
We describe a 2-year-old girl who presented with a large facial hemangioma of the forehead and eyelid, ptosis, microphthalmia, persistent pupillary membrane and pupillary ectopia, ocular motility pathology associated with congenital oculomotor nerve palsy in the affected eye, and bilateral optic disc dysplasia. To the best of our knowledge, this is the first report of a patient with these findings in association with PHACE syndrome.
A 2-year-old girl presented to the pediatric ophthalmology department for evaluation of ocular structures and visual acuity. She had a facial hemangioma on the right forehead and cheek, which had been regressing over time, and ipsilateral ptosis caused by third nerve palsy. Her history included ventriculoperitoneal shunt surgery at age 1 week due to Dandy–Walker malformation. Cranial magnetic resonance imaging showed vascular dilatations in the basilar and right mid-cerebral arteries, and she was being followed up by the pediatric neurosurgery department. Cardiac evaluation, including an echo-cardiogram, showed a vibratory murmur; no other cardiac pathology was noted. Written informed consent was obtained from the parents of the patient for publication of this report.
Ophthalmological examination showed a right-sided facial hemangioma of the forehead, temple, and eyelids (Figure 1A), ipsilateral ptosis (Figure 1B), microphtalmia, corectopia and persistent pupillary membrane extending into the iris (Figure 1C), and optic disc dysplasia in both eyes (Figure 1D), which was more prominent in the right eye. She also had oculomotor nerve palsy that was causing hypotropia and exotropia in her right eye (Figure 2).
(A) The right-sided facial hemangioma of the forehead, temple, and eyelids. (B) Ipsilateral ptosis. (C) Right corectopia and pupillary membrane extending from the superior-nasal portion of the iris causing posterior synechia. (D) Optic disc dysplasia in both eyes, which was more prominent in the right eye. (It was not possible to obtain the optic disc image of the right eye due to the patient's gaze restriction-globe position and pupillary ectopia).
The patient had oculomotor nerve palsy that was causing hypotropia and exotropia in her right eye.
Based on the patient's history of Dandy–Walker malformation, facial hemangioma, cerebral arterial anomalies, and eye abnormalities, she was diagnosed as having PHACE syndrome. Despite her anatomical abnormalities, the patient has been visually progressing. She has been taking propranolol and the hemangiomas have been regressing. At the time of this study, the patient was aged 3 years and still in follow-up, using patching treatment in the left eye to treat amblyopia and pupillary dilatation in the right eye to provide optic axis in the center to prevent amblyopia.
PHACE syndrome is a disorder with a variable phenotype, a female predominance, and a possible X-linked dominance and lethality in males.1,2 Ocular abnormalities have been described in approximately one-third of reported cases, including microphthalmia, iris anomalies, optic atrophy, optic nerve hypoplasia or excavation (morning glory disc spectrum), congenital cataracts, ptosis, strabismus (primarily due to fourth nerve palsy), and glaucoma.1–3 Some rare pathological findings have also been described, including coloboma-like iris defect, persistent pupillary membrane in both eyes, persistent fetal vasculature,4 congenital oculomotor nerve palsy combined with cerebellar hypoplasia,5 and morning glory disc anomaly combined with Horner's syndrome.6
The patient had definite PHACE syndrome in concordance with diagnostic criteria in the literature,7 with multiple ocular pathological findings that were previously described individually in multiple patients, but not combined in a single case. This case is also unusual because multiple ocular pathologies were detected and additional optic nerve pathology was noted in the fellow eye, which has not been previously reported. This case highlights the wide spectrum of possible abnormalities that occur in PHACE syndrome. It is critical that clinicians have a good understanding of the disease process in patients with PHACE syndrome and investigate all of its components to ensure accurate evaluation and effective intervention.
- Metry DW, Dowd CF, Barkovich AJ, Frieden IJ. The many faces of PHACE syndrome. J Pediatr. 2001;139:117–123. doi:10.1067/mpd.2001.114880 [CrossRef]
- Kronenberg A, Blei F, Ceisler E, Steele M, Furlan L, Kodsi S. Ocular and systemic manifestations of PHACES (posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects and coarctation of the aorta, eye abnormalities, and sternal abnormalities or ventral development defects) syndrome. J AAPOS. 2005;9:169–173. doi:10.1016/j.jaapos.2004.08.012 [CrossRef]
- Coats DK, Paysse EA, Levy ML. PHACE: a neurocutaneous syndrome with important ophthalmologic implications: case report and literature review. Ophthalmology. 1999;106:1739–1741. doi:10.1016/S0161-6420(99)90350-0 [CrossRef]
- Lasky JB, Sandu M, Balashanmugan A. PHACE syndrome: association with persistent fetal vasculature and coloboma-like iris defect. J AAPOS. 2004;8:495–498. doi:10.1016/j.jaapos.2004.06.014 [CrossRef]
- Murthy R, Naik MN, Desai S, Honavar SG. PHACE syndrome associated with congenital oculomotor nerve palsy. Strabismus. 2009;17:75–77. doi:10.1080/09273970902798490 [CrossRef]
- Puvanachandra N, Heran MK, Lyons CJ. Morning glory disk anomaly with ipsilateral capillary hemangioma, agenesis of the internal carotid artery, and Horner syndrome: a variant of PHACES syndrome?J AAPOS. 2008;12:528–530. doi:10.1016/j.jaapos.2008.04.005 [CrossRef]
- Metry D, Heyer G, Hess C, et al. Consensus statement on diagnostic criteria for PHACE syndrome. Pediatrics. 2009;124:1447–1456. doi:10.1542/peds.2009-0082 [CrossRef]