What is PHACES (Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac anomalies, Eye abnormalities, and Skeletal anomalies) syndrome?

PHACES Syndrome: A Comprehensive Overview

PHACES syndrome is a rare neurocutaneous disorder characterized by Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac defects and coarctation of the aorta, Eye abnormalities, and Sternal abnormalities or ventral developmental defects. 1

Definition and Pathophysiology

• PHACES is more appropriately termed an association rather than a syndrome, though recent data suggest that chromosomal region 7q33 may provide genetic susceptibility to exhibit the PHACE phenotype 1
• The condition represents a developmental field defect, with an insult occurring early in embryogenesis (likely within the first 3-12 weeks of gestation) 1
• PHACES syndrome is predominantly a congenital vasculopathy, with many features explained as downstream events of arteriopathy with resultant ischemia 1

Diagnostic Criteria

Consensus criteria for diagnosis of PHACES syndrome include:

• Definite PHACES Syndrome:

  • Facial hemangioma >5 cm in diameter plus 1 major criterion or 2 minor criteria 1
  • Hemangioma of the neck or upper torso plus 1 major criterion or 2 minor criteria 1

• Possible PHACES Syndrome:

  • Facial hemangioma >5 cm in diameter plus 1 minor criterion 1
  • No hemangioma plus 2 major criteria 1

Clinical Features

Cutaneous Manifestations

• The hallmark is a large, segmental, often superficial infantile hemangioma (IH), characteristically located on the face, scalp, and/or neck 1
• PHACES syndrome-associated IHs most commonly affect facial segments 1 and/or 3, which confers a particularly high risk of associated central nervous system involvement 1

Extracutaneous Manifestations

1. Cerebrovascular Anomalies (most common extracutaneous manifestation):

   • Major criteria include anomalies of major cerebral arteries, dysplasia of large cerebral arteries, arterial stenosis or occlusion, and persistent trigeminal artery 1
   • Arterial ischemic stroke is a rare but devastating complication, more likely in patients with significant narrowing or nonvisualization of large cerebral arteries 1

2. Structural Brain Abnormalities:

   • Posterior fossa anomalies including Dandy-Walker complex or cerebellar hypoplasia/dysplasia 1, 2
   • Neuronal migration disorders 1
   • Some patients may have subependymal gray matter heterotopia 3

3. Cardiovascular Anomalies (second most common extracutaneous manifestation):

   • Aortic coarctation that differs from classic coarctation (more proximal location, involves arteries feeding upper extremities, affects longer segments) 1
   • Other anomalies include aortic arch anomalies, dysplasia, aneurysm, and aberrant origin of the subclavian artery 1

4. Ocular Abnormalities:

   • Posterior segment abnormalities (persistent hyperplastic primary vitreous, retinal vascular anomalies, optic nerve hypoplasia, coloboma) 1, 4
   • Anterior segment abnormalities (microphthalmia, sclerocornea, cataracts) 1
   • Other findings include strabismus, amblyopia, proptosis, ptosis, and heterochromia 4

5. Sternal/Ventral Abnormalities:

   • Sternal defects, sternal cleft, and supraumbilical raphe 1, 5

6. Endocrine Dysfunction:

   • Some cases report pituitary dysfunction 3

Evaluation and Management

• Clinical examination of the skin and eyes plus detailed imaging of the head, neck, and chest are required for diagnosis 1
• MRI is the preferred imaging modality for evaluating associated anomalies such as spinal dysraphism, anogenitourinary anomalies, and PHACE syndrome 1
• MRA of the head and neck is indicated even in asymptomatic infants due to the potential for progressive vasculopathy and resultant ischemic events 1
• Detailed imaging of the aortic arch is essential due to the unusual and severe nature of aortic anomalies in PHACES syndrome 1

Treatment Approaches

• Treatment of hemangiomas may include:

  • Systemic corticosteroids (prednisolone) 4, 6
  • Propranolol (with caution in patients with cerebrovascular involvement) 6
  • In some cases, combination therapy with propranolol and prednisolone may be advantageous, allowing for introduction of low doses of each with enhanced combined effect 6

• Multidisciplinary approach is recommended for management of PHACES syndrome, particularly for cases with vascular involvement 7

Important Considerations and Pitfalls

• More than 90% of infants with PHACES syndrome exhibit more than one extracutaneous anomaly, although very few manifest the complete spectrum 1
• Careful monitoring by multiple subspecialists is essential, including pediatric ophthalmology, cardiology, and neurology 4
• Caution is needed when using propranolol in patients with cerebrovascular involvement, as hypotension may lead to reduced cerebral blood flow and neurological consequences 6
• LUMBAR syndrome may be considered the "lower half of the body" variant of PHACES syndrome, associated with urogenital, anal, skeletal, and spinal cord anomalies 1