PHACE Syndrome
What is PHACE syndrome?
PHACE syndrome is the association of a large hemangioma usually on the face or neck, in combination with one or more other abnormalities. Every infant diagnosed with PHACE syndrome has different medical needs. Some have mild symptoms while other have more severe symptoms. PHACE syndrome is uncommon but may have been misdiagnosed in the past. It affects girls nine times more often than boys.
The term PHACE is an acronym that refers to a group of abnormal medical findings. When these occur in combination, the diagnosis of PHACE syndrome is made.
PHACE defined:
Posterior fossa- These are brain malformations that are usually present at birth. These brain malformations do not form after the infant is born.
Hemangioma- The hemangioma usually covers a large area on the skin of the head or neck (greater than 5 cm). The term "segmental" is sometimes used to describe these hemangiomas.
Arterial lesions- The abnormalities of the blood vessels in the neck or head.
Cardiac abnormalities/aortic coarctation- These are abnormalities of the heart or the blood vessels that are attached to the heart.
Eye abnormalities.
What causes PHACE syndrome?
There has been a lot of progress in recognizing and understanding PHACE syndrome, but there is no known cause. Researchers at Children's Hospital of Wisconsin, The Medical College of Wisconsin and the Hemangioma Investigator Group have ongoing research studies. These groups recently have published criteria for diagnosis of PHACE syndrome so earlier detection may lead to earlier and safer treatments.
These are examples of hemangiomas that may be seen in infants with PHACE syndrome:
 
How is the diagnosis of PHACE syndrome made?
It is recommended that any infant with a large facial hemangioma be evaluated by a pediatric dermatologist, a pediatric ophthalmologist or a physician who is familiar with PHACE syndrome. If PHACE syndrome is suspected, special radiology tests may be needed. These tests may include an MRI or MRA of the head, neck and chest and an echocardiogram. If the tests are abnormal, the infant should be seen by a multidisciplinary vascular anomalies team. This includes the specialists who are needed to give the infant ongoing care. The pediatric specialists who may be needed to treat these infants include a dermatologist, hematologist/oncologist, ophthalmologist, radiologist, neurologist, geneticist, cardiologist and otolaryngologist who are all familiar with treating this syndrome.
What are the complications of PHACE syndrome?
The hemangiomas found in patients with PHACE syndrome are more likely to have complications. If the hemangioma is near the eye it may cause problems with development of the vision in that eye. The facial hemangioma on these infants is more likely to break open and bleed. When a hemangioma breaks open, it usually is very painful, and the infant needs prompt attention and often, pain medication. Fussiness, poor feeding and difficulty sleeping are all signs that the infant may be having pain.
More serious complications may develop depending on the other anomalies that are found in the infant.
Infants who have PHACE syndrome may be at risk for other neurological problems even after the hemangioma has gotten better. These problems may include migraine headaches, seizures, developmental delays, speech delays and very rarely ischemic strokes. These symptoms may be the result of structural defects or cerebrovascular events from the arterial defects.
Infants with cardiovascular defects need close monitoring by a pediatric cardiologist for ongoing care and treatment. The most common cardiac defects associated with PHACE syndrome are coarctation of the aorta or other aortic arch abnormalities. If severe, the coarctation may require surgery.
Infants need to have frequent visits with an ophthalmologist if there are signs of eye involvement. They may need early treatment to prevent loss of sight.
What is the treatment for PHACE syndrome?
The treatment for PHACE syndrome may vary for each infant. Treatment will depend on the severity of the disease and associated problems.
Medical findings associated with PHACE syndrome:
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Posterior fossa anomalies-brain structure |
- Dandy-Walker complex.
- Cerebellar hypoplasia.
- Subependymal or arachnoid cysts.
- Hypoplasia of cerebrum.
- Hypoplasia of corpus callosum.
- Hypoplasia of septum pellucidum.
- Hypoplasia of vermis.
- Absent foramen lacerum.
- Polymicrogyria.
- Microcephaly.
- Heterotopia.
- Absent pituitary or partially empty sella turcica.
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Hemangioma |
- Face, neck or scalp hemangioma is present in more than 95 percent of patients.
- Size is greater than 5 cm.
- Segmental.
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Arterial lesions-cerebrovascular |
- Dysplasia of the large cerebral arteries.*
- Stenosis, occlusion, absence or moderate to severe hypoplasia of the large cerebral arteries.*
- Aberrant origin or course of the large cerebral arteries.*
- Saccular aneurysms.
- Persistent embryonic arteries.
- Cerebral sinus malformations.
- Sinus pericranii.
- Dural arteriovenous malformations.
- Moyamoya vasculopathy.
- Acute arterial stroke.
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*Internal carotid artery, middle cerebral artery, anterior cerebral artery, posterior cerebral artery or vertebrobasilar system.
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Cardiac/aortic coarctation/cardiovas cular |
- Coarctation or interrupted aortic arch.
- Aneurysms of aortic arch.
- Right aortic arch.
- Double aortic arch.
- Congenital valvular aortic stenosis.
- Aberrant origin of a subclavian with or without a vascular ring.
- Subclavian steal syndrome.
- Anomalous coronary arteries.
- Patent ductus arteriosus.
- Anomalous pulmonary veins.
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- Patent foramen ovale.
- Cor triatriatum.
- Tricuspid atresia/stenosis.
- Dextrocardia.
- Persistent left superior vena cava.
- Ventral and atrial septal defects.
- Pulmonary stenosis.
- Tetralogy of Fallot.
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- Posterior segment abnormalities.
- Retinal vascular abnormality.
- Persistent fetal retinal vessels.
- Iris vessel hypertrophy.
- "Morning-glory" disc.
- Peripapillary staphyloma.
- Optic nerve hypoplasia.
- Anterior segment abnormalities.
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- Microphthalmos.
- Coloboma.
- Congenital cataracts.
- Sclerocornea.
- Iris hypoplasia.
- Exophthalmus.
- Congenital third nerve palsy.
- Horner syndrome.
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Other associated anomalies |
| Ventral developmental |
Miscellaneous |
- Partial or complete agenesis of sternum.
- Sternal cleft or pit.
- Sternal papule.
- Lingual ectopic thyroid.
- Supraumbilical raphe.
- Omphalocele.
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- Pituitary insufficiency.
- Micrognathia.
- Aruricular hypoplasia or agenesis/"low-set" ears.
- Orofacial clefting.
- Spina bifida occulta.
- Esophageal diverticulum.
- Cervical cyst.
- Ipsilateral sensineural hearing loss.
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Research currently focusing on PHACE association (PHACE syndrome)
A Phase II Randomized Clinical Trial Assessing the Efficacy and Safety of Oral Prednisolone vs. Intravenous Vincristine in the Treatment of Infantile Hemangiomas
Infants with large hemangiomas often are treated systemically with oral steroids (Prednisolone) to prevent complications. The best treatment for hemangiomas is not known. Also, the best method to measure the response of hemangioma to treatment is not known. The goals of this study are to determine whether Prednisolone or Vincristine is more effective and safer for treating infants with hemangiomas and to determine if changes on MRI scan are more sensitive than changes on clinical exam for detecting responses to treatment. A total of 50 babies younger than 6 months old with hemangiomas requiring treatment will take part in this study. Participating hospitals include Children's Hospital of Wisconsin, Riley Hospital for Children in Indianapolis and the University of California, San Francisco. Patients enrolling in this study will be randomly assigned to receive either daily Prednisolone by mouth or weekly Vincristine in a vein. Response to treatment will be monitored by clinical exams every two weeks, and by an MRI at study entry as well as six and 12 weeks later. Patients whose hemangiomas have grown by week six will be switched to the other drug to complete a total of 12 weeks of therapy. Side effects of each medication will be monitored closely. Participation in this study will last two years, with 12 weeks of treatment and follow-up visits every two to three months for two years.
Large Facial Hemangioma Study
This study focuses on the presence of PHACE syndrome in children with large facial hemangiomas. The goal of this study is to better understand the risk of this syndrome and to develop guidelines for its evaluation and management. Study subjects will be recruited through the HIG study sites and the Dermatology Clinic at Children's Hospital of Wisconsin. Parents will be interviewed about their personal, medical and family history. Patients will be evaluated for facial hemangiomas with risk of PHACE syndrome. This includes a skin, eye and neurological examination, photograph, MRI of the head, neck and chest, and lab tests requiring samples of blood, urine or stool.
Genetic Basis of Hemangiomas
Genes are linked to many health conditions; however, it is unknown whether genetic predisposition (family history) plays a significant role in the development of infantile hemangiomas, PHACE syndrome or other vascular anomalies. The purpose of this study is to determine if there are genes common to children diagnosed with infantile hemangioma or other vascular anomalies. This information will allow physicians to improve care for affected patients and provide parents with more complete information regarding the cause of their child's condition. All participants will be recruited through the Dermatology Clinic at Children's Hospital of Wisconsin or informational or educational events held within the community. Participation requires one visit lasting 15 to 20 minutes. Enrollment may occur either at the time of clinic visit or, if desired, at a separate research appointment. Researchers will collect either a buccal (cheek cells) or small blood sample and interview parents regarding their personal, medical and family history.
Longitudinal Study of Neurologic, Cognitive and Radiologic Outcomes in PHACE Syndrome
A small group of patients with skin hemangiomas (noncancerous growth of blood vessels appearing as a type of birthmark) on the head and neck may also have one or several disorders associated with PHACE syndrome.
To participate in this trial: (1) Your child must be diagnosed with definite or probable PHACE syndrome (according to the 2009 criteria); (2) Child must be 4, 5 or 6 years of age; (3) You and your child must be available to travel to Children's Hosptial of Wisconsin for scheduled outpatient evaluations during a one- or two-day period (limited travel funds are provided by the study); (4) No drugs are used for this study.
Why is this study important? While it is known that children with PHACE syndrome may have abnormalities of the blood vessels in the brain or structural brain abnormalities, it is not known what the significance of these abnormalities is or how this affects children as they get older. As a result, it is difficult for physicians to counsel parents of infants with PHACE syndrome regarding future expectations or problems that may be encountered in regards to development. This project is the first study to look at specific areas of development in children with PHACE syndrome through neurologic, psychological and cognitive evaluations. The data used from this study will be used in the development of standardized testing to establish clinical guidelines for the management of children with PHACE syndrome. About 30 children will be enrolled in this study. We believe that the information gained in this study will better characterize PHACE syndrome, and establish guidelines for diagnostic neuroimaging of at-risk infants. For more information about this study, please contact the research coordinator, Linda Gaertner, at (414) 456-5769.
For more information regarding these studies or if you are interested in enrolling your child, please call or e-mail Marcia Seefeldt, nurse clinician for the Birthmarks and Vascular Anomalies Center, at (414) 266-3727 |
