Structural malformations of the brain, eye, and pituitary gland in PHACE syndrome

Abstract

PHACE syndrome is the association of segmental facial hemangiomas with congenital arterial, brain, cardiac, and ocular anomalies. Structural brain malformations affect 41-52% of PHACE patients and can be associated with focal neurologic deficits, developmental delays, and/or intellectual disability. To better characterize the spectrum of structural brain and other intracranial anomalies in PHACE syndrome, MRI scans of the head/neck were retrospectively reviewed in 55 patients from the PHACE Syndrome International Clinical Registry and Genetic Repository. All registry patients with a diagnosis of definite PHACE syndrome who had MRI scans of satisfactory quality were included. Of 55 patients, 34 (62%) demonstrated ≥1 non-vascular intracranial anomaly; structural brain malformations were present in 19 (35%). There was no difference in the prevalence of brain anomalies between genders. Brain anomalies were more likely in patients with S1 and/or S2 distribution of facial hemangioma. The most common structural brain defects were cerebellar hypoplasia (25%) and fourth ventricle abnormalities (13%). Dandy-Walker complex and malformations of cortical development were present in 9% and 7%, respectively. Extra-axial findings such as pituitary anomalies (18%) and intracranial hemangiomas (18%) were also observed. Six patients (11%) had anomalies of the globes or optic nerve/chiasm detectable on MRI. Brain malformations comprise a diverse group of structural developmental anomalies that are common in patients with PHACE syndrome. Along with brain malformations, numerous abnormalities of the pituitary, meninges, and globes were observed, highlighting the need for careful radiologic assessment of these structures in the neuroimaging workup for PHACE syndrome.

Keywords: PHACE syndrome; brain malformations; eye abnormalities; magnetic resonance imaging; pituitary gland.

Figure 1

a) Axial T1 post contrast fat saturated image showing hypoplasia of the left cerebellum (arrows) and a large hemangioma in the region of left internal auditory canal (arrowhead). Small hemangioma is also seen in the left masticator space, b) Axial T2 (left panel) and sagittal T1 (right panel) weighted images showing Dandy-Walker spectrum malformation with absence of vermis (black arrow), hypoplasia of the cerebellar hemisphere, and large posterior fossa cyst (white asterisk). Mild hypoplasia of the brainstem (white arrow) is also noted, c) Sagittal T1 weighted image of the brain in the midline showing dysgenesis of the corpus callosum (arrow) and a pericallosal lipoma (arrowhead), d) Axial (left panel) and coronal (right panel) T2 weighted images of the brain show malformation of cortical development (polymicrogyria) in the right frontal lobe. e) Axial T2 (left panel) and coronal T1 (right panel) show dural ectasia in the form of enlargement of the left Meckel’s cave (arrows). Large hemangioma is seen in the left temporal region (arrowheads). Ipsilateral cerebellar hypoplasia is also noted (left panel), f) Pituitary malformations in two different patients. Sagittal T1 weighted image showing hypoplasia of the bony sella and pituitary gland (left panel, arrow). Sagittal T1 weighted image showing ectopic posterior pituitary bright spot (right panel, arrowhead) and hypoplasia of the pituitary gland (arrow). Pituitary stalk is also absent, g) Ocular abnormalities in two children with PHACE syndrome. Axial T2 weighted image showing staphyloma involving the right globe (left panel, arrowhead) and mild hypoplasia of the ipsilateral cerebellum (left panel, arrow). Coronal T2 weighted image showing subchoroidal hemorrhage in the left globe (right panel, arrow).