Hemangiomas are the most common benign tumors of infancy occurring in up to 2.6% of neonates and up to 12% of children by the first year.[3
] Hemangiomas typically present with a phase of rapid proliferation in the first year of life, followed by a slow gradual involution over the next 5–7 years or more. Most hemangiomas remain asymptomatic and can be managed by close observation; however, immediate treatment is indicated for hemangiomas that might cause significant complications such as visual impairment, skeletal deformity, airway obstruction, high-output cardiac failure, bleeding or ulceration.
The association of cervicofacial hemangiomas with vascular and other intracranial malformations was first recognized by Pascual-Castroviejo[4
] in 1978. In 1996, Frieden et al
] introduced the acronym PHACE to describe a neurocutaneous syndrome characterized by Posterior fossa malformations, Hemangiomas, Arterial anomalies, Coarctation of aorta/Cardiac anomalies, and Eye anomalies. The acronym has subsequently been expanded to PHACES to include Sternal clefting or Supraumbilical raphe.[9
] Metry et al
] reviewed 130 cases of PHACES where this neurocutaneous syndrome was found to represent a spectrum of anomalies, and most affected children have only one extracutaneous manifestation.
Intracranial malformations are more frequent when the hemangioma involves the first branch of the trigeminal nerve.[3
] Posterior cranial fossa malformations are present in 74% of cases, although other series quote closer to 50%.[6
] Dandy–Walker malformation is the most common associated developmental abnormality.[3
] Other anomalies include hypoplasia or agenesis of the cerebellum, cerebellar vermis, corpus callosum, cerebrum, and septum pellucidum.[3
] The potential for secondary neurologic sequelae among patients with underlying brain involvement exists, but the actual risk of progressive disease is not known. Burrow et al
] reported progressive neurologic disease among four patients with PHACES syndrome who were neurologically normal until symptoms of hemiparesis, acute onset of seizure, or both developed between 9 and 18 months of age. Neuroimaging revealed cerebral infarction secondary to progressive occlusive arterial changes in all patients.
Hemangiomas in PHACES syndrome are not different from sporadic lesions, but they show a 9:1 female:male ratio compared to the 3:1 ratio for the latter.[6
] They are typically bulky, plaque-like lesions involving several cervicofacial segments, but without being confined by their boundaries, unlike Sturge–Weber syndrome. Left-sided facial hemangiomas predominate (43%), followed by right-sided and bilateral involvement in 29% and 27%, respectively.[3
] Trigeminal division V1 is the most commonly affected dermatome. Extracutaneous hemangiomas occur in 22% of patients with PHACES syndrome, with the subglottis being the most common site.[8
] Subglottic hemangiomas represent 1.5% of congenital abnormalities of the larynx. They are potentially life threatening, with varying degrees of respiratory compromise.[9
] Badi et al
] confirmed that most subglottic hemangiomas are histologically and immunohistochemically infantile hemangiomas (IH) and similar to IH located in other anatomic locations.
The variety and extent of arterial anomalies associated with PHACES syndrome are wide. Arterial anomalies of the head and neck, specifically aneurismal dilatations and anomalous branches of the internal carotid artery, occurred in nearly one-third of cases in one report.[3
] Pascual-Castroviejo et al
] described two patterns of arterial abnormalities: Persistent embryonic arteries (e.g., trigeminal artery) and agenesis of major arteries (e.g., internal carotid or vertebral arteries).
More than one-third of PHACES cases had cardiac and/or aortic anomalies. Coarctation of the aorta was the single most common defect. Multiple cardiac anomalies were described including patent ductus arteriosus, ventricular septal defects, arterial septal defects, pulmonary stenosis, cor triatriatum, tricuspid aortic valve, arterial enlargement, ventricular hypertrophy, tetralogy of Fallot, and patent foramen ovale.[3
] Our patient had three cardiac anomalies: Ventricular septal defect, hypertrophic interventricular septum, and tricuspid regurgitation. The latter two findings were not reported previously.
Ophthalmologic findings in PHACES syndrome are seen in 30% of cases with predominance of anterior segment abnormalities.[11
] The most common anomalies include choroidal hemangiomas, cryptophthalmus, exophthalmus, colobomas, posterior embryotoxon, and optic atrophy.[12
Sternal defects and supraumbilical raphe were encountered in 43 patients with PHACES syndrome.[1
] Matry et al
] reported three patients with subtle sternal pits without underlying soft-tissue or bony loss in a series of 14 patients with PHACES syndrome. Interestingly, in our case, both sternal pit and supraumbilical raphe were present. Sternal clefts in PHACES can be classified into three categories: Superior, inferior, and complete.
In the presented case, the cutaneous and airway hemangiomas responded well to the megadose of oral prednisolone. Other treatment options of airway hemangiomas might include systemic vincristine, laser therapy, tracheotomy, or surgical excision.[13
] A recent meta-analysis study evaluating the effectiveness of propranolol versus steroid, CO2
laser, or vincristine showed that propranolol is the most effective treatment for infantile airway hemangioma.[14
] Prognosis of PHACES syndrome is not known for certain as presentations vary and management of extracutaneous problems is system dependent.
In conclusion, PHACES syndrome should be considered in any infant presenting with a large, segmental facial hemangioma. Children at risk should receive careful ophthalmologic, cardiac, and neurologic assessment with special attention to possible airway involvement. The necessary radiologic and endoscopic imaging studies should be carried out when indicated.