PHACE syndrome is a rare condition in which a large facial hemangioma — a type of vascular birthmark — appears alongside structural problems in the brain, blood vessels, heart, and eyes. The acronym stands for Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac defects/Coarctation of the aorta, and Eye abnormalities; a trailing “S” is sometimes added for Sternal or ventral midline defects.‌1PubMed. PHACES syndrome: a review of eight previously unreported cases with late arterial occlusions Because PHACE can affect so many organ systems at once, a baby who appears to have “just” a large birthmark may actually need brain imaging, heart evaluation, and eye exams in the first months of life.
The Facial Hemangioma That Signals Something Deeper
Not every infantile hemangioma raises concern for PHACE. The ones that do tend to be large (generally over 5 cm), segmental rather than round and focal, and located on the face or scalp. Researchers have mapped these hemangiomas into four facial segments. The frontotemporal segment (S1) covers the lateral forehead, anterior temporal scalp, and often the upper eyelid while sparing the central forehead. The maxillary segment (S2) involves the upper lip and medial cheek. The mandibular segment (S3) covers the jaw, chin, and preauricular area and often extends bilaterally in a “beard” pattern. The frontonasal segment (S4) spans the central forehead, nasal bridge, nasal tip, and philtrum.2JAMA Dermatology. Mapping of Segmental and Partial Segmental Infantile Hemangiomas of the Face and Scalp
The mandibular (S3) segment deserves special mention. In one study of children with airway hemangiomas, about three-quarters had bilateral S3 involvement, though some presented with hemangiomas limited to the lower lip and chin, and a smaller group had only one-sided involvement.3JAMA Otolaryngology–Head & Neck Surgery. Clinical Spectrum and Risk of PHACE Syndrome in Cutaneous and Airway Hemangiomas This matters practically: a beard-distribution hemangioma should prompt evaluation not only for PHACE but also for possible airway involvement, since hemangiomas in the S3 region can grow internally and obstruct breathing.
It is worth noting that PHACE can occur without a visible hemangioma at all. The consensus diagnostic criteria acknowledge that some patients present with hemangiomas on the neck, chest, or arm, or occasionally with no cutaneous hemangioma, and can still meet the diagnostic threshold if enough other features are present.4Pediatrics. Consensus Statement on Diagnostic Criteria for PHACE Syndrome
Arterial Anomalies and the Brain
The “A” in PHACE is among the most clinically significant letters in the acronym. In a study of 70 children with PHACE who all had confirmed arterial abnormalities, more than half had multiple types of arteriopathy. The most common was dysgenesis (abnormal development of the artery wall), found in about 56% of patients. Abnormal vessel course or origin followed at roughly 47%, narrowing at 39%, and complete absence of a vessel segment at 20%. A fifth of the children also had primitive embryonic connections between the carotid and vertebrobasilar systems — remnants of fetal vascular architecture that normally disappear before birth.5PubMed Central. Cervical and intracranial arterial anomalies in 70 patients with PHACE syndrome
These arterial problems are not just anatomical curiosities. They carry a real stroke risk, even in young children. A systematic review found that absent, underdeveloped, or occluded major cerebral arteries were significant risk factors for arterial ischemic stroke, especially when more than one vessel was involved or when coarctation of the aorta was also present.6PubMed. Stroke in children with posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities (PHACE) syndrome: a systematic review of the literature A more recent computational flow study identified severe tortuosity (extreme twisting of an artery) as the strongest predictor of cerebrovascular accidents in PHACE, with an odds ratio of 30.7Scientific Reports. Numerical flow experiment for assessing predictors for cerebrovascular accidents in patients with PHACES syndrome That finding is from a small dataset, so the confidence interval is wide, but the direction is striking: the more distorted the vessel path, the greater the risk.
Posterior Fossa and Structural Brain Malformations
The “P” stands for posterior fossa malformations, meaning structural problems in the back of the brain, particularly the cerebellum. In a neuroradiology review of 17 patients, half had structural brain abnormalities. The most common was underdevelopment of one cerebellar hemisphere, and in every case the affected side matched the side of the facial hemangioma. Dandy-Walker variant, a related malformation involving the cerebellum and the fluid-filled space behind it, was the second most common finding. A smaller number of patients had abnormalities higher in the brain, including cortical dysplasia and migrational anomalies.8American Journal of Neuroradiology. PHACES Association: A Neuroradiologic Review of 17 Patients
Other posterior fossa anomalies reported in PHACE include vermian hypoplasia (underdevelopment of the central part of the cerebellum) and cerebellar cortical dysgenesis.9PubMed. Posterior fossa and arterial abnormalities in patients with facial capillary haemangioma: presumed incomplete phenotypic expression of PHACES syndrome Some researchers have also noted enlargement of the internal auditory canal on imaging, which may be part of a generalized underdevelopment of the posterior fossa and surrounding bone rather than a standalone anomaly.10American Journal of Neuroradiology. Enlargement of the Internal Auditory Canal and Associated Posterior Fossa Anomalies in PHACES Association
The ipsilateral pattern — the side of the brain affected matching the side of the hemangioma — is a recurring theme across studies and is one of the features that points toward a developmental disruption affecting a specific embryonic territory rather than a random combination of defects.
Heart and Aortic Defects
About 41% of patients in a large international PHACE registry had cardiovascular anomalies. Among those with heart or aortic involvement, coarctation of the aorta or interrupted aortic arch was the most common finding, present in 45%. The coarctation seen in PHACE is distinctive: rather than the typical localized narrowing found in isolated cases, PHACE-associated coarctation tends to involve a long segment of the transverse aortic arch with adjacent areas of aneurysmal widening. More than half of the patients with coarctation required surgical or catheter-based intervention, most within the first few months of life.11PubMed Central. Congenital Cardiac, Aortic Arch, and Vascular Bed Anomalies in PHACE Syndrome (From The International PHACE Syndrome Registry)
Intracardiac defects occurred as well, with ventricular septal defects being the most common (about 31% of those with cardiovascular findings). Complex congenital heart disease was rare, seen in only 3 of the 62 patients with cardiovascular involvement.12PubMed Central. Congenital Cardiac, Aortic Arch, and Vascular Bed Anomalies in PHACE Syndrome (From The International PHACE Syndrome Registry) Because coarctation can be life-threatening in a newborn but is treatable when caught, echocardiography is a standard part of early evaluation.
Eye Abnormalities
Eye involvement in PHACE is less common than brain or heart findings but not negligible. In one study that examined ophthalmic outcomes, about 12% of patients met the PHACE-specific ocular diagnostic criteria, which include optic nerve anomalies, retinal vascular anomalies, and lenticular (lens) abnormalities. Additional findings that fell outside the formal diagnostic criteria — things like persistent pupillary membranes, iris or choroidal hemangiomas, and Peters anomaly — were also seen. Overall, about one in seven patients had a structural eye abnormality, and in every case the affected eye was on the same side as the facial hemangioma.13PubMed. Ophthalmic involvement in PHACES syndrome: prevalence, spectrum of anomalies, and outcomes
Rarer presentations include persistent fetal vasculature, a condition in which embryonic blood vessels inside the eye fail to regress. In one documented case, imaging revealed a stalk of tissue extending from the optic nerve to a displaced lens, confirmed on MRI.14PubMed Central. PHACE(S) Syndrome with Ocular Involvements and No Periocular Hemangioma Eye problems in PHACE can affect vision significantly, which is why ophthalmologic screening is recommended even when the hemangioma does not involve the eye area.
Sternal and Ventral Midline Defects
The “S” in PHACES refers to sternal clefts, supraumbilical raphe (a line of skin changes running from the chest to the navel), and other ventral midline abnormalities. These defects are among the less frequent features of the syndrome but are diagnostically useful because they are uncommon in isolation. A sternal cleft in a baby who also has a facial hemangioma is a strong prompt to investigate for the full spectrum of PHACE.15PubMed Central. Phenotypic spectrum and management of sternal cleft: literature review and presentation of a new series The typical picture is a gap in the breastbone covered by thin skin, sometimes accompanied by a midline abdominal raphe extending down to the umbilicus.16Korean Journal of Pediatrics. A girl with sternal malformation/vascular dysplasia association
Making the Diagnosis
PHACE is diagnosed clinically, not through a single genetic test. The published consensus criteria divide the diagnosis into two tiers: definite PHACE and possible PHACE. A definite diagnosis requires a characteristic segmental facial or scalp hemangioma (or one larger than 5 cm) plus at least one major criterion or two minor criteria across the relevant organ systems — cerebrovascular, structural brain, cardiovascular, ocular, and ventral/midline. A possible diagnosis requires the hemangioma plus one minor criterion.17Pediatrics. Consensus Statement on Diagnostic Criteria for PHACE Syndrome
In practice, this means that when a baby presents with a large segmental facial hemangioma, the workup typically includes brain and vascular MRI with angiography, echocardiography, and an ophthalmologic exam. The goal is to identify which, if any, of the associated anomalies are present so that surveillance and treatment can be tailored.
Distinguishing PHACE From Sturge-Weber Syndrome
One of the most important clinical distinctions in early infancy is between PHACE and Sturge-Weber syndrome. Both conditions involve facial vascular lesions and brain abnormalities, and in the newborn period a hemangioma in its earliest flat, red stage can look a lot like a port-wine stain.18Seminars in Pediatric Neurology. PHACE syndrome: A review The two conditions differ in their underlying vascular pathology: Sturge-Weber involves a capillary malformation (which is present at birth, does not grow, and does not fade on its own), while PHACE involves an infantile hemangioma (which may be absent or minimal at birth, proliferates rapidly in the first weeks, and eventually involutes). Their associated brain findings also differ. Clarifying which condition is present matters because the monitoring, treatment, and long-term prognosis diverge substantially.
Treating the Hemangioma Safely
Oral propranolol, a beta-blocker, is the standard first-line treatment for complicated infantile hemangiomas. Its use in PHACE has been debated because of a theoretical concern: lowering heart rate and blood pressure in a child with already-narrow cerebral arteries could further reduce blood flow to the brain and trigger a stroke. This concern was reasonable enough that many clinicians hesitated or used the drug cautiously.
A study comparing 76 infants with PHACE who received oral propranolol against 726 propranolol-treated infants without PHACE found no strokes, transient ischemic attacks, or cardiovascular events in the PHACE group. The rate of serious adverse events was not significantly different between the two groups.19PubMed Central. Evaluating the Safety of Oral Propranolol Therapy in Patients With PHACE Syndrome That does not mean the theoretical risk is zero — it means the accumulated clinical experience has not borne it out, and propranolol is generally considered safe in this population when used with appropriate monitoring. Most specialists still recommend baseline brain and vessel imaging before starting the drug, so that any pre-existing vascular compromise is documented.
Long-Term Outcomes and Quality of Life
The hemangioma itself typically fades over years, but PHACE is not a condition that children simply “outgrow.” A multicenter study of patients older than 10 found that about 72% reported persistent or troublesome headaches at some point, and roughly 45% had received a migraine diagnosis. Nearly half had headaches severe enough to warrant a neurology referral. Larger hemangiomas (10–15 cm) were associated with a higher likelihood of headaches compared with somewhat smaller ones.20The Journal of Pediatrics. Multicenter Study of Long-Term Outcomes and Quality of Life in PHACE Syndrome after Age 10
Learning differences were reported in about 45% of patients, and roughly 39% needed special educational support or an individualized education plan. The strongest predictors of learning difficulties were structural brain anomalies, posterior fossa malformations, and eye anomalies. Severe developmental delay affecting daily life was uncommon (about 4%), and all of those cases involved significant structural brain findings.21The Journal of Pediatrics. Multicenter Study of Long-Term Outcomes and Quality of Life in PHACE Syndrome after Age 10 A separate, smaller neurodevelopmental study found that while group-level scores did not diverge dramatically from population norms in most domains, about 16% of children had at least one score in the impaired range and another 12% had two or more scores in the at-risk range.22PubMed. Neurodevelopmental Outcomes in Children with PHACE Syndrome
Quality of life scores, measured using a standardized global health instrument, were lower than population norms by at least one standard deviation.23The Journal of pediatrics. Multicenter Study of Long-Term Outcomes and Quality of Life in PHACE Syndrome after Age 10 Living with a visible facial difference, the burden of medical appointments, and the functional effects of brain or eye anomalies all contribute. For families, the practical implication is that follow-up should extend well beyond the period of hemangioma treatment and include educational, neurological, and psychosocial support.
Endocrine Problems That Can Go Unnoticed
An underappreciated aspect of PHACE is its potential to affect the hormonal system. The pituitary gland sits at the base of the brain in a region that can be structurally abnormal in PHACE patients, and cases of growth hormone deficiency, central hypothyroidism, secondary adrenal insufficiency, and even panhypopituitarism have been reported.24PubMed Central. A case of phace syndrome and acquired hypopituitarism? In one documented case, brain MRI showed an empty sella (a pituitary fossa without visible gland tissue), and testing revealed deficiency across multiple hormonal axes.25PubMed Central. A case of phace syndrome and acquired hypopituitarism?
Hypopituitarism is listed as a minor diagnostic criterion for PHACE, though it remains extremely rare — as of one recent report, only about four cases were documented in the literature.26JAAD Case Reports. Congenital panhypopituitarism unmasked by PHACE screening Rarity, however, does not mean unimportant. Growth hormone deficiency can cause poor growth that gets attributed to something else, and unrecognized adrenal insufficiency can be dangerous during illness or stress. Some specialists now recommend monitoring growth parameters and thyroid function at regular intervals in all PHACE patients, especially those with abnormal pituitary anatomy on MRI.27PubMed. A case of PHACE syndrome with growth hormone deficiency and abnormal thyroid functions
What Causes PHACE
There is no single known gene or mutation behind PHACE, and the condition is not inherited in a straightforward way. The vast majority of cases are sporadic. Several hypotheses have been explored: some researchers proposed a link to X-chromosome inactivation (since PHACE is much more common in girls), but a dedicated study did not support that idea. Another line of thinking involves somatic mosaic mutations in neural crest cells — the embryonic cell population that gives rise to much of the face, blood vessels, and connective tissue of the head. If a mutation occurs early enough in these cells and they migrate along specific developmental segments, that could explain why the hemangioma and associated defects tend to cluster on one side of the body.28PubMed Central. PHACE syndrome: looking backward and forward
A genetic study using high-resolution arrays in 98 PHACE patients found 10 chromosomal regions with unusual copy number variation, scattered across multiple chromosomes. These were not mutations shared by all patients but rather rare gains or losses that may each contribute to the condition in a subset of individuals.29PubMed Central. PHACE syndrome: looking backward and forward The working model is that PHACE results from a combination of genetic susceptibility and a disruption during a narrow window of early embryonic vascular development. The science here remains genuinely uncertain.
Why Coordinated Care Matters
Because PHACE can involve dermatology, neurology, cardiology, ophthalmology, endocrinology, and developmental pediatrics all at once, fragmented care is a real risk. A child may be followed by a dermatologist for the hemangioma without anyone checking for cerebrovascular anomalies, or a cardiologist may manage the coarctation without awareness of the headache and learning issues that emerge later. Case reports consistently emphasize that a phased, multidisciplinary approach leads to better outcomes — catching coarctation before it becomes an emergency, identifying learning needs before a child falls behind in school, and screening for endocrine deficits before growth failure becomes severe.30PubMed Central. A Multimodal Approach to a Complex PHACES Patient With Progressive Infantile Hemangioma: A Case Report and Review of Literature For families navigating a new diagnosis, knowing that the birthmark is the visible tip of a condition with many quieter components can help ensure the right specialists are brought in early.