A prospective study of PHACE syndrome in infantile hemangiomas: Demographic features, clinical findings, and complications

• Published in: American journal of medical genetics. Part A Vol. 140A; no. 9; pp. 975 - 986
• Main Authors: Metry, D.W., Haggstrom, A.N., Drolet, B.A., Baselga, E., Chamlin, S., Garzon, M., Horii, K., Lucky, A., Mancini, A.J., Newell, B., Nopper, A., Heyer, G., Frieden, I.J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-05-2006; Wiley-Liss
• Subjects: Abnormalities, Multiple - diagnosis; Abnormalities, Multiple - pathology; Airway Obstruction - complications; Biological and medical sciences; Brain - abnormalities; Child; Child, Preschool; Cohort Studies; Ear Diseases - complications; Eye Diseases - complications; Facial Neoplasms - complications; Facial Neoplasms - pathology; Female; Heart Defects, Congenital - complications; Heart Defects, Congenital - pathology; hemangioma; Hemangioma - complications; Hemangioma - pathology; Humans; Infant; Male; Medical sciences; Neurocutaneous Syndromes - complications; Neurocutaneous Syndromes - pathology; Neurology; pediatric stroke; PHACE; PHACES; Prospective Studies; Syndrome; Vascular diseases and vascular malformations of the nervous system; Human; hemangioma; Pediatrics; Nervous system diseases; Stroke; PHACE; Cardiovascular disease; Congenital disease; Cerebral disorder; Prospective; Vascular disease; PHACES; Symptomatology; Angioma; Phenotype; pediatric stroke; Central nervous system disease; Complication; PHACE syndrome; Complex syndrome; Child; Cerebrovascular disease; Public health
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.31189

PHACE (OMIM no. 606519) is a neurocutaneous syndrome that refers to the association of large, plaque‐like, “segmental” hemangiomas of the face, with one or more of the following anomalies: posterior fossa brain malformations, arterial cerebrovascular anomalies, cardiovascular anomalies, eye anomalies, and ventral developmental defects, specifically sternal defects and/or supraumbilical raphe. The etiology and pathogenesis of PHACE is unknown, and potential risk factors for the syndrome have not been systematically studied. The purpose of this study was thus to determine (1) the incidence of PHACE and associated anomalies among a large cohort of hemangioma patients, (2) whether certain demographic, prenatal or perinatal risk factors predispose infants to this syndrome, and (3) whether the cutaneous distribution of the hemangioma can be correlated to the types of anomalies present. We undertook a prospective, cohort study of 1,096 children with hemangiomas, 25 of whom met criteria for PHACE. These 25 patients represented 20% of infants with segmental facial hemangiomas. Compared to previous reports, our PHACE patients had a higher incidence of cerebrovascular and cardiovascular anomalies. Two developed acute arterial ischemic stroke during infancy, while two with cardiovascular anomalies showed documented evidence of normalization, suggesting that both progressive and regressive vascular phenomena may occur in this syndrome. Correlation to the anatomic location of the hemangioma appears to be helpful in determining which structural abnormalities might be present. A comparison of demographic and perinatal data between our PHACE cases and the hemangioma cohort overall showed no major differences, except a trend for PHACE infants to be of slighter higher gestational age and born to slightly older mothers. Eighty‐eight percent were female, a finding which has been noted in multiple other reports. Further research is needed to determine possible etiologies, optimal evaluation, and outcomes. © 2006 Wiley‐Liss, Inc.