PHACE syndrome

What is PHACE syndrome?

PHACE syndrome is an association between infantile haemangiomas and malformation of eyes, heart, major arteries, and brain. PHACE was first described by Dr Ilona Freidan in 1996.

The acronym PHACE stands for:

• Posterior fossa brain malformations
• Haemangiomas, particularly large, segmental facial lesions
• Arterial anomalies
• Cardiac (heart) anomalies and coarctation of the aorta
• Eye abnormalities and Endocrine abnormalities

PHACES syndrome is PHACE syndrome plus:

• Sternal cleft, supraumbilical raphe, or both

Sternal cleft 

PHACES — segmental facial haemangioma 

PHACES — segmental haemangioma 

How common is PHACE syndrome?

PHACE syndrome is rare. PHACE syndrome affects girls nine times more often than boys.[1] One study has suggested that PHACE may be as common, if not more common, than Sturge-Weber syndrome.[2]

What are the signs and complications of PHACE syndrome?

Infants with PHACE have:

• Large segmental haemangioma on the face, scalp, or neck, or rarely, of the arm or trunk.
  • The haemangiomas may ulcerate and bleed and can be painful.
  • Haemangiomas near the eye can lead to loss of sight.
  • Haemangiomas within the ear or auditory structures within the brain can lead to loss of hearing.
• Abnormalities of blood vessels or other structures within the brain.
  • These may lead to strokes, seizures and developmental delay, particularly in motor function (movement).
• Heart problems include narrowing of the aortic arch, complex arch anomalies, or septal defects (‘hole in the heart’).
• PHACE syndrome may also present with hormone (endocrine) abnormalities.

What is the significance of segmental haemangiomas?

The specific site or segment affected by a haemangioma can indicate the likely problems in underlying tissues.

Haemangiomas on the face affect four primary segments:

• Segment 1 (frontotemporal) involves part of the forehead and the temples.
  • These are at higher risk for associated brain malformations.
• Segment 2 (maxillary) encompasses the cheek area.
• Segment 3 (mandibular) involves the jaw and chin.
  • Mandibular haemangiomas are associated with a greater risk of cardiac anomalies and haemangiomas in the airway, which may cause breathing difficulties.
• Segment 4 (frontonasal) involves the middle of the forehead and nose.

Lumbosacral haemangiomas of the lower back (see LUMBAR) or around the anus and genitals (see PELVIS) have been associated with anomalies of the genitals, spine, anus, and kidneys. These are not classified within the PHACE spectrum.

How is a diagnosis of PHACE syndrome made?

PHACE(S) syndrome is a clinical diagnosis, i.e., a collection of signs and symptoms or diagnostic criteria are necessary to make a diagnosis of PHACE syndrome. A Consensus Statement on Diagnostic Criteria for PHACE Syndrome published in 2009, proposed major and minor criteria within various organ systems.[3]

• Cerebrovascular system
• Structural brain anomalies
• Cardiovascular anomalies
• Ocular abnormalities
• Ventral or midline defects

What causes PHACE syndrome?

There is no known cause of PHACE syndrome. The relationship of abnormalities found in PHACE syndrome suggests it is a problem in embryonic development at a specific critical time, probably between 3 and 12 weeks gestation when blood vessels are developing.[3]

What investigations should be done in PHACE syndrome?

Infants with large haemangiomas of the face or scalp (>24 cm²) should undergo investigations to establish whether they have PHACE syndrome. These may include:

• Magnetic resonance imaging (MRI) and magnetic resonance angiogram (MRA) of the head and neck
• Computed tomography angiogram (CTA) of the brain, neck, and chest.
• Eye examinations
• Ear examination and audiometric testing
• Echocardiogram, an ultrasound test of the heart and blood vessels.

What is the treatment for PHACE syndrome?

The management of PHACE syndrome will vary depending on which defects are found in each affected organ system. Care requires a multidisciplinary team and may include a dermatologist, ophthalmologist, haematologist, oncologist, radiologist, neurologist, cardiologist, and otolaryngologist.

Treatment for the haemangioma may involve oral propranolol, systemic steroids, surgery and/or laser therapy.

Can infants with PHACE syndrome be safely treated with propranolol?

Severe blood vessel abnormalities in children with PHACE syndrome may restrict the use of propranolol in the treatment of haemangiomas because propranolol may reduce blood pressure (hypotension). Careful evaluation of major blood vessels in the brain and heart should be undertaken if this treatment is considered.