PHACE(S), syndrome 

[MIM 606 519]

(Pascual-Castroviejo type 2 syndrome)

Acronym for Posterior fossa, cephalic Hemangioma, intra-extracranial Arterial anomalies, Coarctation of the aorta, Eye anomalies and abnormalities of Sternum if (S) )

Rare. X-linked dominant transmission with strong female prevalence (90 %).

Neuro-cutaneous syndrome (see table for the diagnostic criteria) associating:

-        posterior fossa malformations: Dandy-Walker, cortical dysplasia, microcephaly, ...

-        one or more large facial hemangioma with a segmental topography: 20 % of children with a large facial hemangioma present at least one of the anomalies associated with PHACES

-        anomalies of the cerebral arteries which are divided into 4 categories: 1) dysplasia (52 %): segmental longitudinal dilations of the internal carotid, kinking, anevrysmal ectasies; 2) stenosis (45-48 %), hypoplasia or agenesis of vessels at the base of the skull 3) aberrant origin or pathway (28-44 %) ; 4) persistence of embryonic anastomoses, especially the trigeminal artery (12-16 %); risk of stroke (especially in case of corticosteroid therapy). Sometimes Moyamoya type anomalies.

-        cardiac defects: aortic coarctation (14.5 %), often over a long segment and accompanied by anomalies of the brachiocephalic vessels, right aortic arch, patent ductus arteriosus, ASD, VSD, aneurysm of the ascending aorta...

-        eye anomalies on the same side as the hemangioma: microphthalmia, retinal anomalies, coloboma, glaucoma, morning glory syndrome (see this term).


Sometimes there can be:

-        sternal cleft or a sus-umbilical raphe

-        congenital hypothyroidism with lingual thyroid


There are also frequently extracutaneous hemangiomas  the most common location being the subglottic hemangioma (50 %). It is recommended to perform a diagnostic endoscopy of the upper airway in any PHACE(S) child presenting with respiratory problems or facial hemangioma with a beard distribution. The indication of any treatment with propranolol should be individualized, taking into account the possibility of vascular cerebral (risk of stroke) and/or cardiac anomalies


PHACE syndrome

facial hemangioma  > 5 cm + 1 major criterion

or 2 minor criteria

possible PHACE syndrome

facial hemangioma  > 5 cm + 1 minor criteria

or

hemangioma of the neck or upper chest + 1 major criterion or 2 minor criteria

or

absence of hemangioma and 2 major criteria



Organ/system

Major criteria

Minor criteria

cerebrovascular

abnormalities of the large cerebral arteries:

-        dysplasia

-        occlusion or stenosis with or without Moyamoya arterial

-        aplasia or variable hypoplasia

-        aberrant origin or pathway

-        saccular aneurysms

-        persistence of the trigeminal artery

persistence of other embryonic arteries than the trigeminal artery: otic artery, hypoglossal artery, intersegmental artery anterior to the atlas

brain

anomaly of the posterior fossa:

Dandy-Walker, cerebellar hypoplasia or dysplasia

extra-axial lesions compatible with an intracranial hemangioma; anomaly of the median line; neuronal migration disorder

cardiovascular

aortic arch anomaly: coarctation, aneurysm, aberrant origin of the subclavian artery

VSD, double aortic arch

ocular

posterior segment abnormalities: fetal vasculature of the vitreous body, optic nerve hypoplasia, coloboma, peripapillary staphyloma, Morning Glory type anomaly  of the optical disc

anterior segment anomalies: cataract, coloboma, microphthalmia

median structure

sternal cleft

supraombilical raphe

ectopic thyroid

hypopituitarism


Anesthetic implications:

echocardiography to evaluate the cardiovascular malformations. Possible presence of a subglottic hemangioma (stridor ?). Significant risk of stroke with or without convulsions: maintain adequate cerebral perfusion pressure and avoid hypocapnia: transcutaneous monitoring of cerebral saturation could be useful. Sometimes patients under beta-blockers to treat the hemangiomas.


References : 

-        Javault A, Metton O, Raisky O, Bompard D, Hacheni M, Gamondes D, Ninet J, Neidecker J, Lehot JJ, Cannesson M.
Anesthesia management in a child with PHACE syndrome and agenesis of bilateral carotid arteries. 
Pediatr Anesth 2007; 17: 989-93.

-        Hartemink DA, Chiu YE, Drolet BA, Kerschner JE. 
PHACES syndrome: a review. 
Int J Pediatr Otorhinolaryng 2009; 73: 181-7.

-        Metry D, Heyer G, Hess C, Garzon M et al. 
Consensus statement on diagnostic criteria for PHACE syndrome. 
Pediatrics 2009; 124: 1447-56.

-         Gross BC, Janus JR, Orvidas LJ. 
Response of infantile airway and facial hemangiomas to propranolol in a patient with PHACES syndrome. 
Int J Pediatr Otorhinolaryng Extra 2012; 7: 183-9.

-        Shah MS, Verghese ST
When faced with anesthetizing an infant with PHACES: watch out for an airway-occluding subglottic hemangioma !
A&A Case Reports 2017; 9:334-54 

-        Durr ML, Meyer AK, Huoh KC, Frieden IJ, Rosbe KW.
Airway hemangiomas in PHACE syndrome.
The Laryngoscope 2012; 122: 2323-9.

-        Shah MS, Verghese ST.
When faced with anesthetizing an infant with PHACE syndrome: watch out for an airway-occluding subglottic hemangioma!
A&A Case Reports 2017; 9: 334-5 

-        Escarza BS, Cruz-Beltran S, Lessans G, Austin TM, Lam HV.
Are pediatric patients with PHACE association at high risk for anesthetic complications?
Pediatr Anesth 2021; 31:39-41.


Updated: February 2021