Unilateral Facial Lesion in an Infant With Known Vermian Hypoplasia

A baby girl is born at 38 + 4 weeks via uncomplicated spontaneous vaginal delivery. Prenatal course is significant for vermian hypoplasia and maternal Beckwith-Wiedemann syndrome. Physical exam reveals an erythematous, blanchable, left-sided facial patch in the distribution of the V1 and V2 branches of the trigeminal nerve with clear demarcation at the midline (Figure 1). Per maternal report, a faint lesion was present at birth but deepened in color over the first hours of life.The baby has a reassuring neurologic exam and initiates breastfeeding without difficulty. Brain magnetic resonance imaging (MRI) reveals left-sided cerebellar hypoplasia (ipsilateral to facial lesion) and asymmetric enlargement of the left Meckel’s cave (Figures 2 and 3). Ophthalmic evaluation finds no abnormalities of the left eye aside from an extension of the facial lesion to the eyelid. Midline workup reveals an aneurysmal atrial septum and small secundum atrial septal defect with no abnormalities on the abdominal ultrasound. After consulting with ophthalmology, cardiology, neurology, dermatology, and genetics, her medical team discharges her on day 3 of life. She sees genetics outpatient but does not undergo germline testing due to limited diagnostic yield with her ultimate diagnosis.She returns to the dermatology clinic at 3 weeks of life by which point her patch has thickened and deepened in color. She has mild left eye swelling leading to decreased spontaneous opening, and thus is readmitted for propranolol initiation. Computed tomography angiogram identifies no additional vascular anomalies of the head or neck.The differential diagnosis of a segmental facial patch in a newborn includes capillary malformation (previously called a port wine stain) and infantile hemangioma precursor. Given her unilateral cerebellar hypoplasia, a port wine stain raises concern for Sturge Weber syndrome, whereas a hemangioma does so for PHACES (posterior fossa malformations, hemangioma, arterial anomalies, coarctation of the aorta/cardiac defects, and eye abnormalities syndrome).After a discussion among multiple experts including dermatology and neurology, she is diagnosed with PHACES. This conclusion hinged upon the diagnosis of her patch. While the 2 can appear similar early in life, a fully formed red patch at birth favors capillary malformation. On the other hand, darkening and thickening over time suggests hemangioma.Infantile hemangiomas are the most common benign tumor of childhood, occurring in approximately 5% of infants.1 In about 50% of cases, there is no evidence of hemangioma at birth, and it becomes apparent in the first few weeks. In the other 50%, there is a visible precursor lesion: a faint erythematous patch, telangiectatic red patch, bruise-like area, or pale area of vasoconstriction. Infantile hemangiomas tend to grow rapidly over the first months of life (typically complete when aged 6 months) followed by a period of stability (until aged 1 year) and then slow resolution (complete in 90% of patients when aged 4 years).2.Coined by Frieden et al in 1996, PHACES is speculated to be a vascular neoplasm caused by a cephalic neuroectodermal defect in embryogenesis and overexpression of vascular growth factors.3 PHACES has a female predominance and includes a constellation of clinical findings seen in approximately 30% of patients with large segmental facial hemangiomas.3 The diagnostic criteria for PHACES include a facial hemangioma > 5 cm in diameter and 1 major or 2 minor criteria involving abnormalities from the following categories: cerebrovascular, brain structure, cardiovascular, ocular, and midline.4,5Vascular anomalies—dysgenesis, agenesis, aberrant vessels, and retained embryonic vessels—are the most common comorbidities in PHACES, typically affecting medium to large arteries of the chest, neck, and head.5–7 Vascular changes are considered progressive, including aneurysmal and steno-occlusive changes, Moyamoya arteriopathy, and eventually, arterial ischemic stroke with a median age of onset around 8 to 18 months.8,9 Neurologic abnormalities include structural differences of the posterior fossa (Dandy-Walker malformation, arachnoid cysts, cerebellar atrophy/hypoplasia) and midline structures (corpus callosum, septum pellucidum, optic nerve/chiasm) along with malformations of cortical development (polymicrogyria, gray matter heterotopia, cortical dysplasia) and intracranial hemangiomas (internal auditory canal, cerebellopontine angle).5,6,10–12 Reported rates of structural brain anomalies range from 35% to 52%12–14 and are often ipsilateral to the cutaneous lesions.5–7 Cardiovascular abnormalities often involve the arch or subclavian artery. Less common findings are ophthalmic comorbidities (<20% of patients), including posterior segment anomalies and microphthalmia5 and extracranial midline abnormalities, most of which are sternal defects.5Evaluation of a large segmental facial hemangioma should include an MRI of the brain and neck; magnetic resonance angiogram of the head, neck, and chest; echocardiogram; and ophthalmologic evaluation. PHACES has a known association with endocrine abnormalities (most commonly thyroid dysfunction and growth hormone deficiency). Therefore, children with PHACES require ongoing vigilance for growth, developmental milestones, and symptoms of hypothyroidism or adrenal insufficiency in addition to early endocrine assessment if a patient has structural pituitary abnormalities.5 While most structural anomalies in PHACES are static, progressive hydrocephalus and posterior fossa cysts warrant neurosurgical consultations. Vascular abnormalities are stratified by a risk for ischemic strokes with recommended follow-up ranging from none to routine biannual imaging and possible secondary stroke prevention or neurosurgical consultation.5Long-term differences in those with PHACES include a heightened risk for developmental delays, seizures, headaches, movement disorders, and hearing abnormalities depending on their intracranial abnormalities.5,11,13,15 Patients with PHACES warrant close neurologic surveillance and early referrals to therapies, audiologists, and neurosurgeons if indicated.Large segmental facial hemangiomas associated with PHACES typically follow aggressive growth patterns. They have a high risk for functional impairment (particularly with eyelid involvement), ulceration, scarring, and disfigurement. Thus, systemic treatment with propranolol is recommended.2This baby successfully initiates propranolol with occasional episodes of mild hypoglycemia that resolve with slower dose increases. She is currently meeting developmental milestones and sees physical and occupational therapists monthly, who note only occasional postural asymmetry, a finding related to her unilateral cerebellar hypoplasia.16 Her subspecialty follow-ups also include repeat echocardiogram with cardiology, neurodevelopmental surveillance with neurology, hemangioma management with dermatology, and ophthalmology exams that have found no structural changes. She does not follow with neurosurgery given her absence of progressive structural brain changes.The trajectory of a facial lesion over the first weeks of life can be pivotal in distinguishing hemangiomas from capillary malformations, which, in turn, can differentiate associated syndromes.A large facial patch in a newborn should prompt further evaluation including head and neck vascular imaging, echocardiogram, and ophthalmologic exam.Hemangiomas may or may not be present at birth but grow thicker and darker in the first few weeks of life.A baby with PHACES requires long-term, multidisciplinary follow-up because of the progressivity of the vascular and dermal manifestations.SummaryThis case highlights the necessity of maintaining a high index of suspicion for associated cardiac and vascular anomalies in babies with segmental facial patches. This baby demonstrates the importance of close follow-up and interdisciplinary communication, as segmental infantile hemangiomas and capillary malformations can be initially indistinguishable but reveal themselves over time, guiding clinicians, in this case, to the diagnosis of PHACES.