PHACE Syndrome

At a glance

PHACE is a neurocutaneous syndrome and an acronym that stands for Posterior fossa brain malformations, Hemangiomas of the face, Arterial anomalies, Cardiac anomalies, and Eye abnormalities Syndrome. The addition of an S (abnormalities of the sternum) to the PHACE Syndrome becomes PHACES Association and refers to the association of ventral developmental defects, such as Sternal clefting or Supraumbilical raphe.

Synonyms

PHACES Association; Pascual Castroviejo Syndrome Type 2.

Incidence

Rare; more than 250 cases described.

Genetic inheritance

X-linked dominant transmission with almost 9 out of 10 patients are female.

Pathophysiology

Unknown; possibly a developmental error between the sixth and eighth week of gestation.

Diagnosis

This syndrome should be considered in any infant presenting with a large, segmental, plaque-type facial hemangioma; careful cardiac, neurologic, and ocular examination is mandatory. A consensus document describes major and minor criteria for diagnosis of PHACE.

Major criteria: Arterial anomalies: Anomaly of major cerebral or cervical arteries; dysplasia of the large cerebral arteries; arterial stenosis or occlusion with or without moyamoya collaterals; absence or moderate-severe hypoplasia of the large cerebral and cervical arteries; aberrant origin or course of the large cerebral or cervical arteries except common arch variants; persistent carotid-vertebrobasilar anastomosis. Brain: Posterior fossa brain anomalies; Dandy-Walker complex; other hypoplasia/dysplasia of the mid and/or hind brain. Cardiovascular: Aortic arch anomalies; coarctation of the aorta; aneurysm; aberrant origin of the subclavian artery with or without a vascular ring. Ocular: Posterior segment abnormalities; persistent hyperplastic primary vitreous; persistent fetal vasculature; retinal vascular anomalies; morning glory disc anomaly; optic nerve hypoplasia; peripapillary staphyloma. Midline anomalies: Anomaly of the midline chest and abdomen (sternal defect, sternal pit, sternal cleft, supraumbilical raphe).

Minor criteria: Arterial anomalies: Aneurysm of any of the cerebral arteries. Brain: Midline brain anomalies; malformation of cortical development. Cardiovascular: Ventricular septal defect, right aortic arch/double aortic arch; systemic venous anomalies. Ocular: Anterior segment abnormalities; microphthalmia; sclerocornea; coloboma; cataracts. Midline anomalies: Ectopic thyroid hypopituitarism; midline sternal papule/hamartoma. Definite diagnosis of PHACE Syndrome is made based on the occurrence of a hemangioma greater than 5 cm in diameter plus one major or two minor criteria or hemangioma of the neck, upper trunk and proximal upper extremity plus two major criteria. A possible diagnosis of PHACE is made based on the occurrence of a hemangioma greater than 5 cm in diameter plus one minor criteria or hemangioma of the neck, upper trunk, and proximal upper extremity plus one major or two minor criteria or no hemangioma plus two major criteria.

Clinical aspects

Seventy percent of patients have only one extracutaneous manifestation of ...