PHACE syndrome

PHACE syndrome, also known as cutaneous hemangioma–vascular complex syndrome or Pascual-Castroviejo type II syndrome, is a phakomatosis that comprises of:

• P: posterior fossa malformations (e.g. Dandy-Walker malformation)

• H: hemangiomas

• A: arterial anomalies

• C: coarctation of the aorta and cardiac anomalies

• E: eye (ocular) anomalies

When sternal clefting and/or supraumbilical raphe are also present it is termed PHACES syndrome.

Epidemiology

PHACE syndrome is nine times more common in females ⁹.

Clinical presentation

Clinical diagnosis of PHACE syndrome requires the presence of a characteristic segmental hemangioma or hemangioma >5 cm on the head (face or scalp) plus 1 major criterion or 2 minor criteria ⁵. 

Major criteria anomalies:

• arterial: 

  • anomaly of major cerebral / cervical arteries (ICA, ACA, MCA, PCA, vertebral, basilar)

  • dysplasia of the large cerebral arteries (tortuosity, kinking, dolichoectasia)

  • arterial stenosis or occlusion with or without moyamoya collaterals

  • absence or moderate-severe hypoplasia of the large cerebral arteries

  • aberrant origin or course of the large cerebral arteries (except common aortic arch variants such as bovine aortic arch)

  • persistent carotid-vertebrobasilar anastomosis (persistent trigeminal, hypoglossal, proatlantal, or otic)

• structural brain: 

  • posterior fossa anomalies 

  • Dandy-Walker complex 

  • midbrain/hindbrain hypoplasia/dysplasia

• ocular: 

  • posterior segment anomalies

  • persistent hyperplastic primary vitreous

  • persistent fetal vasculature

  • retinal vascular anomalies

  • morning glory disc anomaly

  • optic nerve hypoplasia

  • peripapillary staphyloma

• cardiovascular:

  • aortic arch anomalies (except common variants such as bovine arch)

  • aortic coarctation

  • aberrant origin of subclavian artery

  • aortic aneurysm

• ventral or midline:

  • sternal defects or supraumbilical raphe

Minor criteria:

• arterial:

  • intracranial aneurysm

• structural brain:

  • midline anomalies

  • cortical malformations 

• ocular:

  • anterior segment anomalies

  • sclerocornea

  • cataract

  • coloboma

  • microphthalmia

• cardiovascular:

  • ventricular septal defect

  • right aortic arch / double aortic arch

  • systemic venous anomalies

• ventral or midline:

  • hypopituitarism

  • ectopic thyroid

  • sternal papule/hamartoma

Pathology

The pathogenesis of PHACE syndrome is unknown, and the condition is thought to be sporadic in etiology ^9,10. While it has been widely hypothesized that PHACE syndrome may have a genetic etiology through somatic mutation(s) in early embryogenesis, no such mutations have been identified ^9,10. No familial cases have been described ¹¹.

Historic and etymology

Initially, this syndrome was described as an association of large cutaneous hemangiomas of the head and anomalies of the cerebral vasculature by Pascual-Castroviejo in 1978 ^7,8. Subsequently, the name PHACE syndrome was coined by Ilona Frieden et al ².