PHACES the acronym used to describe a collection of symptoms first described collectively in the literature by Dr. Ilona Frieden in 1996 as a syndrome. The largest review of PHACES related symptoms was published in 2001 in the Journal of Pediatrics by physicians at Baylor University and University of California San Francisco . This publication reported on the cases of 14 patients examined and an additional 116 cases reported in the literature. To date there have been only 200 published cases of PHACES. Greater then 90% of these cases are females and greater then 25% of these patients have presented with a segmental infantile hemangioma. However; patients presenting with one skin hemangioma and one or more of the following symptoms may be characterized as having the PHACES Association.

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PHACES presents with a wide collection of varied symptoms. Both the presentation and the severity of the symptoms differ greatly. The Structural Brain Malformations that have been reported include, Dandy Walker Cysts, Cerebellar hypoplasia/atrophy; underdevelopment of the cerebellum, encephalomalacia or a softening of the brain and dysgenesis/agenesis of vermis, which is the absence of a structure of the brain separating the lobes of the cerebral hemispheres. There can also be an absence or underdevelopment of the cerebrum, corpus callosum or septum pellucidum of the brain. Malformations may include subependymal or arachnoid cysts, frontal lobe calcifications, polymicrogyria, microcephaly and the absence of the foramen lacerum.

The associated cerebrovascular arterial anomalies that have been seen in patients classified as having the PHACES association are, carotid artery anomalies, abnormal arterial branches, absence of the carotid artery and either stenosis or occlusion off the carotid artery. Aneurysm formation is also noted. There have been reported cases of the presence of an embryonic artery in patients classified as having PHACES.

An even more varied collection of eye anomalies have been classified as having the association to PHACES, microphthalmos, retinal vascular abnormality, persistent fetal retinal vessels, atrophy of the retina, hypertrophy of the iris vessel or an underdeveloped iris, underdeveloped optic nerve, congenital cataracts, palsy of the 3 rd facial nerve, optic disc anomalies, and Horner Syndrome; a sinking, drooping of one eyeball or eye lid with constriction of the pupil and flushing of the face.

The cardiac defects that are seen in PHACES include atrial and ventricular septal defects, ductus arteriosus; a condition that leaves a fetal artery open from the heart to the aorta, shunting blood away from the lungs, pulmonary stenosis, abnormal pulmonary veins and valve abnormalities. In less then 20 reported cases in the literature there have been aortic arch anomalies presented. These anomalies include aneurysms of the aorta, or subclavian artery. They were reported as an interrupted aortic arch, congenital valvular aortic stenosis, dextropostion of the aorta and anomalies of the coronary arteries.

In March of 1993 Dr. Francine Blei of NYU Medical Center published an article in Pediatric Dermatology of an infant presenting with a midline abdominal scar, sternal atresia an a large cutaneous facial hemangioma. The midline reddish-purple abdominal scar was vertical, healted and hypertrophic. The facial hemangioma grew rabidly and was of concern to the physicians following the patient. The hemangioma ulcerated, interfered with feeding and it was believed it would have continued to grow without medical intervention. Currently there are few other reports of the sternal defects, supraumbilical raphe or amphalocele; a birth defect in which part of the intestine is covered only by a thin transparent membrane, protruding outside the abdomen.

Rarely miscellaneous defects have been reported to be seen in the PHACES Association. They include, low set ears, small jaw, facial clefting, endocrine system abnormalities and cerebrospinal abnormalities.

The many associated abnormalities of PHACES are long and varied. This complicates both the diagnosis and management of this classification of patients. Further complicating factors included the related physiological sequelae. Of the >50% of the prior published and newly reported PHACE patients with brain anomalies at least one half will have neurological complications. The congenital cerebrovascular arterial anomalies give rise to an occlusion or narrowing to the terminal internal carotid and or proximal segment of the anterior cerebral artery. These patients are likely to be at an increase risk of stroke and other neurological complications. According to Dr. Denise Metry, Texas Children's Hospital in her presentation at the NIH Infantile Hemangioma Workshop, April 7-9, 2005, of the 19 cases she reviewed where stroke was reported between the ages of birth -17 years of age the mean age was 40 months. A statistical note was posted that 2 of these patients suffered stroke post-operatively. Clinically the stroke is often reported as a seizure with cerebral infarction. It can develop in-utero. Most often the strokes are seeing during the proliferative phase of an infantile hemangioma growth. Of concern is that stroke due to the PHACES association may be under reported.

The most common reported symptom of this association is that 90% of the patients have a large segmental Infantile Hemangioma. A correlation of the presentation of the facial hemangioma to regions of the face seems to indicate that location of the hemangioma is related to the other symptoms. Unilateral hemangioma presenting above the eye, forehead and top of head may have a correlation with anomalies of the head and neck while hemangiomas presenting in the chin, neck and beard pattern distribution may be association with the incidence of sternal and cardiac abnormalities. Facial hemangiomas in the cheek region seem to have a combined association of symptoms.

There are other atypical symptoms of the PHACES association followed as well. These included segmental infantile hemangioma in locations other then the face, infantile hemangioma that are localized in both facial and non-facial locations and the absence of a cutaneous infantile hemangioma.

  Physicians involved with the Hemangioma Investigative Group which reviewed the cases of 1056 patients with infantile hemangioma including those with the symptoms associated with PHACE(s) prospectively are examining the direction at which research should be steered in order to better understand this classification of vascular anomaly related disorder. The pathogenesis of PHACES implies a developmental field defect which is suggested by the varied spectrum of anomalies and the relationship between the presenting hemangioma and the cerebrovascular/aortic anomalies. When the abnormality actually occurs is also of question and it is suggested that the defects probably give rise in the first trimester, (3-12 weeks gestation). What is not understood is if this is due to a single gestational defect or multifactorial embryological developmental progression of events. We do not know who is at risk for the development of complications associated with PHACES. Research needs to look at if there are any predictors of stroke neurological complications and whether there are any means of prevention. Better understanding of these issues will help direct which patients need cardiac imaging and neurological imaging studies.

  In the mean time patients presenting with a large segmental infantile hemangioma of the head and neck should be evaluated by a vascular anomalies team or physician experienced in the management of vascular anomalies with a multi-disciplinary view. In the presence of central nervous system, arterial, cardiac, and eye abnormalities head and neck MRI/MRA should be considered. Neurological and Cardiac examinations may be included in the evaluation of symptoms for PHACES. Opthalmological examinations and comprehensive skin examinations should also be included in the evaluation. Once diagnosed; management by a multidisciplinary team will allow for communication between the medical disciplines and with the family. Maintaining cardiac and neurological stability is the goal as well as managing the often aggressive growth of the Hemangioma. In the 1999 Baylor study the facial Hemangioma was treated with medical management and was at writing responding well to treatment. Some cases reviewed in the literature demonstrated a dramatic response to high dose prednisone but re-growth was noted following a taper from the dosage and the lesions were still a significant concern at 1 year of age. A few cases where laser and or surgery were used in the first year had a more notable improvement at 1 year, similar to other facial Hemangioma management strategies. However the other abnormalities found in PHACES sometimes preclude the cosmetic options that are available to children that do not present with complication symptoms

  PHACES was first reported as a syndrome nearly 10 years ago. It is now suggested that rather then a syndrome PHACES is an association of a wide collection of symptoms that vary in both presentation and severity. The criteria for PHACES are a cutaneous hemangioma and at least one more of a long list of abnormalities. What was once thought to be unrelated anomalies are now thought to be part of the PHACES Association. Parents of children concerned about this association should consult their physician and ask for a referral to a Vascular Anomalies Treating Center .

References:

Frieden IJ, Reesev V., Cohne D. Phaces, ARCH Dermatol 1996;132;307-311

Metry D, Metry DW, Dowd CF, Barkovich AJ, Frieden IJ. The Many Faces of PHACE Syndrome. J. Pediatric 2001 Jul:139(1):117-23

Metry Denise, Segmental Hemangiomas and Structural Anomlaies, Infantile Hemangiomas Current Knowledge, Future Directions, National Institute of Health April 7-9, 2005

NOTE:  NOVA is dedicated to the education, advocacy and research of PHACES.  In 2006 we donated money through the Caitlin Moncrief Memorial to the Texas Children's Hospital's PHACES patient registry.  In 2007 we will be enhancing our support of the PHACES community.

There is a new site on the internet for PHACES Support.  It is managed by parents of children with PHACES.  These children have a wide range of symptoms in both type and severity.  It serves as a great support for families.  Many of these families attended the NOVA Family Conference in April 2007 which allowed them to meet for the first time

NOVA PROVIDES THIS INFORMATION TO FAMILIES AS A RESOURCE. IT IS NOT INTENDED TO ENGAGE IN THE PRACTICE OF MEDICINE OR TO REPLACE THE PHYSICIAN. NOVA DOES NOT CLAIM TO HAVE MEDICAL KNOWLEDGE. NOVA DOES NOT ENDORSE ANY PARTICULAR PHYSICIAN, TREATING FACILITY OR TREATMENT PROTOCAL. IN ALL CASES NOVA AND ITS BOARD OF DIRECTORS RECOMMENDS THAT YOU SEEK THE OPINION OF A PHYSICIAN EXPERIENCED IN THE MANAGEMENT OF HEMANGIOMAS AND VASCULAR MALFORMATIONS. 

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