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:

• cerebrovascular: 
  • anomaly of major cerebral 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 arteries
  • aberrant origin or course of the large cerebral arteries
  • persistent trigeminal artery
  • saccular aneurysms of any cerebral arteries
• brain: posterior fossa anomalies 
  • Dandy-Walker complex 
  • cerebellar hypoplasia/dysplasia
• ocular: posterior segment anomalies
  • persistent fetal vasculature
  • retinal vascular anomalies
  • morning glory disc anomaly
  • optic nerve hypoplasia
  • peripapillary staphyloma
  • coloboma
• cardiovascular:
  • aortic arch anomaly
  • aberrant course or origin of supra-aortic arteries
• ventral or midline: sternal defects or supraumbilical raphe

Minor criteria:

• cerebrovascular: persistent embryonic artery (carotid-vertebrobasilar anastomosis) other than trigeminal artery
• brain:
  • extra-axial intracranial hemangioma
  • midline anomaly
  • neuronal migration disorder 
• ocular: anterior segment anomalies
  • sclerocornea
  • cataract
  • coloboma
  • microphthalmia
• cardiovascular:
  • ventricular septal defect
  • right aortic arch
• ventral or midline:
  • hypopituitarism
  • ectopic thyroid

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.