Posterior Fossa Brain Malformations Research Articles

Cross-sectional evaluation of Spanish-language resources on websites of US dermatology organizations

Cross-sectional evaluation of Spanish-language resources on websites of US dermatology organizations

Arterial Spin-Labeling Perfusion for PHACE Syndrome.

Arterial stroke is a rare-but-reported complication in patients with posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities (PHACE) syndrome. Currently, stroke risk is inferred by the severity of arterial anomalies identified on MRA, though no evidenced-based data exist. The purpose of our study was to determine whether arterial spin-labeling MR imaging perfusion can detect alterations in CBF in patients with PHACE syndrome. Records were reviewed from 3 institutions for all patients with PHACE syndrome who underwent arterial spin-labeling from 2000 to 2019. CBF was qualitatively investigated with arterial spin-labeling to determine whether there was decreased or normal perfusion. Arterial anomalies were characterized on MRA imaging, and parenchymal brain findings were evaluated on conventional MR imaging sequences. Forty-one patients with PHACE syndrome had arterial spin-labeling imaging. There were 30 females and 11 males (age range, 7 days to 15 years). Of the 41 patients, 10 (24%) had decreased CBF signal corresponding to a major arterial territory. Ten of 10 patients had decreased CBF signal in the anterior circulation, 2/10 had decreased anterior and posterior circulation CBF signal, 2/10 had decreased bilateral anterior circulation CBF signal, and 1/10 had globally decreased CBF signal. Forty of 41 (97.5%) patients had at least 1 arteriopathy, and in those with decreased CBF signal, the arteriopathy corresponded to the CBF signal alteration in 10/10 patients. Arterial spin-labeling can potentially characterize hemodynamic changes in patients with PHACE syndrome.

Dieulafoy lesions and PHACE syndrome

Dieulafoy's lesion (DL) is a small gastrointestinal (GI) mucosal erosion due to an abnormally large caliber and persistent submucosal arteriole. Typically occurring in adults, they are an extremely rare cause of GI bleeding in pediatrics. We report a case of multiple jejunal DLs in a 9-year-old girl with posterior fossa brain malformations, hemangiomas, arterial lesions, cardiac abnormalities, eye abnormalities (PHACE) syndrome, and the first described use of rapamycin in the treatment of pediatric DLs.

PHACE syndrome: Infantile hemangiomas associated with multiple congenital anomalies: Clues to the cause.

Infantile hemangiomas (IH) are the most common vascular tumor of infancy with an estimated 80,000 annual diagnoses in the United States. The genetic mechanisms underlying IH and the related multi-organ birth defect syndromes, PHACE (an acronym for Posterior fossa brain malformations, segmental facial Hemangiomas, Arterial anomalies, Cardiac defects, Eye anomalies, and sternal clefting or supraumbilical raphe) and LUMBAR (an acronym for Lower body hemangiomas, Urogenital anomalies, Myelopathy, Bone deformities, Anorectal malformations/Arterial anomalies, Renal anomalies) remain unsolved. With advances in next generation sequencing (NGS), genomic alterations have been identified in a wide range of vascular anomaly syndromes. We hypothesize that PHACE is a genetic disorder, caused by somatic mutations, likely in cancer genetic pathways. Identification of the genetic etiology will lead to improved diagnosis in PHACE syndrome and development of targeted therapies for IH and related congenital anomalies.

Anesthesia for Complex Cardiovascular Surgery in a Patient With PHACES Syndrome and Review of the Literature

NFANTILE HEMANGIOMAS ARE a common benign vascular tumor occurring in 5% to 10% of infants 1 and resolve without complication or medical intervention. A subgroup of patients with hemangiomas have associated structural anomalies causing significant physiologic changes such as posterior fossa brain malformations, hemangiomas of the face, arterial cerebrovascular, cardiovascular, and eye anomalies that occur along with ventral defects (sternal defects or supraumbilical raphe). 1,2 These anomalies constitute the acronym PHACES, formally defined in 1996 by Freiden, 2 yet suspicion of the syndrome arose in 1978. It was recognized that certain cervicofacial hemangiomas were associated with intracranial abnormalities. 3 Patients are stratified into 2 categories: PHACES syndrome or possible PHACES syndrome depending on the number and type of anomalies. 4 Approximately 20% of infants with large cervicofacial hemangiomas 5 will have one of the associated anomalies of PHACES. 1 Two-thirds of patients with large segmental hemangiomas have at least 1 extracutaneous manifestation and 42% have at least 2. 4 Cerebrovascular anomalies are most common among PHACES-syndrome patients (87%) followed by cardiovascular (37%), eye (16%), ventral developmental defects (sternal defects; 7%-21%), as well as endocrine abnormalities (6%). 6,7 Hemangiomas are not always detectable in PHACES syndrome. 4 They can be absent or reduced in size due to

A PHACES Syndrome Unmasked by Propranolol Interruption in a Tetralogy of Fallot Patient: Case Report and Extensive Review on New Indications of Beta Blockers

Infantile hemangiomas (IHs) are the most common benign tumors of infancy and usually they don't require specific therapy. In 10-20% of cases IHs are able to generate complication and medical/surgical intervention is needed. For many decades standard treatment consisted in oral or intralesional corticosteroids until Leaute-Labreze and colleagues published the first report on the efficacy of propranolol for cutaneous infantile hemangiomas in 2008. IHs can be sometimes part of complex syndrome. Here we report the case of a patient with tetralogy of Fallot operated at 5 month of age who stopped propranolol treatment for hypoxic spells and unusually developed facial and subglottic IHs configuring the diagnosis of PHACES syndrome (posterior fossa brain malformations, hemangioma, arterial anomalies, cardiac defects and/or aortic coarctation, ocular anomalies and sternal defects). To our knowledge this is the first report in the international literature of a delayed appearance of an infantile hemangioma involving the skin and the airways (PHACES syndrome). The pathophysiological explanation relies on the mechanism of action of propranolol which seems to act initially with vasoconstriction, down-regulating proangiogenetic factors and inducing endothelial cell apoptosis. Many decades since their introduction β-blockers are useful in a growing group of diseases. The pleiotropic effect of β-adrenoceptors antagonists is not yet deeply understood, residing in neurohormonal regulation systems and angiogenesis and proving to be an effective treatment from cardiovascular to oncological illnesses.

PHACES syndrome with moyamoya vasculopathy – a case report

"PHACES" (OMIM 606519) is a neurocutaneous disorder, and facial hemangiomas are the hallmark of this syndrome. The syndrome encompasses posterior fossa brain malformations, facial hemangiomas, arterial anomalies, aortic coarctation, cardiac anomalies, eye abnormalities, and sternal defects.

A case of phace syndrome and acquired hypopituitarism?

BackgroundPHACE is a neurocutaneous syndrome associated with: Posterior fossa brain malformations, large “segmental” facial hemangiomas, arterial cerebrovascular-, cardiovascular-, and eye anomalies.Case vignetteWe are reporting a girl with PHACE syndrome. The patient had a congenital right-sided facial hemangioma with plaque-morphology. At age 11 years and 2 months she presented with short stature, markedly decreased growth velocity and signs and symptoms suggestive of hypothyroidism. Magnetic Resonance Imaging (MRI) of the brain revealed complex structural and cerebrovascular arterial anomalies, including an empty sella. Testing of pituitary function revealed multiple pituitary dysfunctions, including absolute growth hormone deficiency, hypogonadotropic hypogonadism, central hypothyroidism, and secondary adrenal insufficiency.ConclusionsThis case suggests the necessity to screen all patients with PHACE syndrome and intracranial malformations for pituitary dysfunction at regular intervals.

Ischemic Stroke in PHACE Syndrome

PHACE is a syndrome defined by its acronym: Posterior fossa brain malformations, Hemangiomas, Arterial anomalies, Coarctation of the aorta/Cardiac

Stroke in Children With Posterior Fossa Brain Malformations, Hemangiomas, Arterial Anomalies, Coarctation of the Aorta and Cardiac Defects, and Eye Abnormalities (PHACE) Syndrome

PHACE is an acronym for posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities. Several case reports of arterial ischemic stroke (AIS) in individuals with PHACE have been published, but risk factors for AIS in PHACE have not been clearly defined. The objective of this article is to review all cases of stroke in PHACE in children and describe clinical characteristics that may be associated with an increased risk of AIS. A literature and registry search was conducted to identify patients with PHACE who had experienced AIS. Data were analyzed to determine age of onset, presenting signs and symptoms, and clinical features among this cohort compared with PHACE without AIS. Twenty-two individuals with PHACE and AIS were identified. Imaging of the arteries of the head and neck was reported in 20 of 22. Narrowing or nonvisualization of at least 1 great cerebral vessel was present in 19 of 20 and of those, 15 had ≥ 2 vessels involved. Aortic arch anomalies were reported in 13 of 22 individuals. Aplasia, hypoplasia, or occlusion of a major cerebral artery appears to be a significant risk factor for AIS in children with PHACE, especially when >1 vessel is involved or if there is coarctation of the aorta.

PHACE/S syndrome: A syndromic infantile segmental hemangioma

PHACES syndrome is a neurocutaneous disorder characterized by posterior fossa brain malformations, hemangiomas, cardiac anomalies and coarctation of aorta, eye anomalies ± sternal clefts. All reported cases are sporadic and notably common in females. The underlying cause is unknown. Here is described, one of the twin baby with characteristic features of PHACE syndrome. The presence of large segmental hemangioma, especially on face should prompt the primary care provider to act early, to prevent complications related to facial hemangiomas and other associated anomalies.

Posterior Fossa Neoplasm and PHACES Syndrome

A 4-year-old girl with PHACES syndrome (posterior fossa brain malformations, hemangiomas, arterial anomalies, cardiac anomalies/coarctation of the aorta, eye abnormalities, and sternal clefting/supraumbilical raphe) developed a cerebellar pilocytic astrocytoma 18 months after resolution of her neck, ear, and thoracic hemangiomas. Because cutaneous hemangiomas may have involuted by the time a patient is diagnosed with a central nervous system neoplasm, it seems possible that in other such patients the association may have gone unrecognized. Cerebellar pilocytic astrocytoma may be a rare manifestation of the posterior fossa malformations of PHACES.

Letters to the Editor

4 June 2008 Dear Editor, PHACE SYNDROME: A CONSTELLATION OF CEREBRAL AND CARDIOVASCULAR ANOMALIES AND SEGMENTAL HAEMANGIOMAS PHACE syndrome is an uncommon neurocutaneous syndrome that manifests with multi-system involvement. It refers to the association of large, plaque-like, ‘segmental’ haemangiomas of the face, posterior fossa brain malformations, arterial cerebrovascular anomalies, cardiovascular anomalies, eye anomalies and ventral developmental defects.1 This letter describes a male baby who was born to a 41-year-old mother by elective section at term gestation and who weighed 2.88 kg. A prenatal diagnosis of posterior fossa malformation had been made at a 19-week anomaly scan. The infant was delivered breech by LSCS with forceps lift-out and was noted to have extensive bruising on left side of the face with an ipsilateral facial palsy. Over the next week the bruising was replaced by fine telangiectasia, which became darker and evolved into a confluent segmental facial haemangioma in the distribution of trigeminal cranial nerve extending into the oral cavity (Fig. 1). The important differential diagnosis at this stage was Sturge-Weber syndrome. Left sided segmental haemangioma with oral mucosal extension. MRI brain was consistent with Dandy Walker malformation. In addition, a soft tissue mass encircling cranial nerves VI and VII (possible acoustic neuroma, Fig. 2) along with hypoplasia of left vertebral artery was noted. The facial haemangioma was seen to extend internally to the left cavernous sinus, the extraconal spaces of the left eye and the superior mediastinum. While carotid Doppler showed no evidence of stenosis, the echocardiogram showed features consistent with coarctation of aorta. The ophthalmology review was unremarkable, showing no evidence of raised intraocular pressure or retinal detachment/optic neuropathy. He was started on laser therapy for the surface hemangioma after which it showed signs of gradual resolution. He was readmitted at 8 weeks of age with stridor and bronchoscopy revealed a large sub-glottic haemangioma obstructing most of the airway, which was managed by placement of a tracheostomy tube. MRI brain showing soft tissue mass encircling VI and VII nerves. While the acronym PHACE (OMIM 606519) was suggested by Frieden in 1995,2 the exact incidence of PHACE syndrome is unknown. Pathogenesis too is unknown, while the constellation of anomalies generally represents a ‘developmental field defect’, whereby an insult in embryogenesis at a critical time gives rise to similar developmental outcomes.3 The timing of these errors in morphogenesis occurs early, probably between 3 and 12 weeks of gestation, prior to or during early vasculogenesis. The syndrome represents a spectrum of disease, with few infants manifesting the entire constellation of anomalies, some components appearing later. The marked female preponderance (>80%) suggests a possibility of X-linked inheritance with lethality in males.1 Both sporadic and X-linked or autosomal inheritance patterns are reported, the X-linked form being typically bilateral and diffuse, and often associated with a mutation of filament A gene (FLNA) on Xq28.4 The hallmark of PHACE syndrome, a large, segmental facial haemangioma, may involve one to several facial dermatomes, and an early presentation may be mistaken for the port wine stain associated with the Sturge-Weber syndrome. Structural and cerebrovascular brain malformations occur in at least half. Posterior fossa malformations, including the Dandy-Walker complex, are the most common, and others include agenesis of corpus callosum and polymicrogyria. Developmental delay is a common association. Cerebrovascular defects present primarily as carotid artery anomalies, but also include aberrant/anomalous origins and aneurysm of cerebral vessels. The cerebrovascular anomalies, especially carotid artery anomalies, are of particular concern because of predisposition to progressive arterial occlusion and stroke.5, 6 Cardiac anomalies include coarctation of the aorta and septal defects, while ophthalmologic anomalies include retinal vascular abnormalities, optic nerve atrophy, and colobomas, among others. Infants with PHACE syndrome could represent up to 20% of infants with segmental facial hemangiomas, and both progressive and regressive vascular phenomena may occur in this syndrome.1 The most common therapeutic option directed at regression of haemangioma is prednisolone/ methylprednisolone, while others include topical steroids, pulsed dye laser, interferon alpha, vincristine, excision surgery and wound care.1 To summarise, a segmental hemangioma may be an initial presentation of PHACE syndrome, and a high index of suspicion and thorough investigation would optimise management.

A comparison of disease severity among affected male versus female patients with PHACE syndrome

PHACE syndrome (Online Mendelian Inheritance in Man database No. 606519) refers to the association of large, plaquelike, or segmental hemangiomas of the face, with one or more of the following anomalies: posterior fossa brain malformations, arterial cerebrovascular anomalies, cardiovascular anomalies, eye anomalies, and ventral developmental defects, specifically sternal defects, supraumbilical raphe, or both. The underlying pathogenesis of PHACE is unknown. A strong female predominance exists, leading some to suggest the possibility of X-linked dominant inheritance, with lethality in male patients. However, no familial cases have been reported, and disease severity among affected male patients has not been systematically studied. We compared the incidence of syndrome-associated anomalies between 17 new and 42 published reports of male patients with PHACE versus 213 published reports of female patients with PHACE. A statistically significant difference was found only for structural brain anomalies, which were somewhat more common in male patients. This was a retrospective study. Information was limited on some new and many previously reported cases. Overall, our results show no convincing trend toward greater or lesser disease severity among affected male patients with PHACE.

Reticular Infantile Hemangioma of the Limb Can Be Associated with Ventral‐Caudal Anomalies, Refractory Ulceration, and Cardiac Overload

We describe six patients with an uncommon variant of infantile hemangioma that we have termed reticular, occurring in the extremity, which were associated with intractable ulceration, anogenito-urinary-sacral anomalies, and sometimes cardiac overload. The extreme end of the spectrum is exemplified by a male neonate who presented with a stained, enlarged, pulsatile lower extremity, and cardiac failure. He also had hepatic hemangiomas and ambiguous genitalia. Progressive soft tissue necrosis and bony destruction necessitated amputation. The histopathologic features differed from those of typical infantile hemangioma: infiltrative (not lobular) and involving fascia, muscle, and bone. The mid-spectrum is illustrated by five females with reticular infantile hemangioma of the lower limb, buttock, and perineum. Four of these infants had a ventral-caudal anomaly, including omphalocele, recto-vaginal fistula, solitary/duplex kidney, imperforate anus, and tethered cord; one infant also had hepatic hemangiomas. Deep ulcerations healed following corticosteroid therapy; one patient required skin graft for closure of a thigh wound. The minor end of the spectrum is exemplified a patchy lesion in the distal limb. The reticular variant of infantile hemangioma can be confused with other vascular anomalies in the limb, such as capillary malformation, cutis marmorata telangiectasia congenita, diffuse arteriovenous malformation (Parkes Weber syndrome) and capillary-lymphatico-venous malformation (Klippel-Trenaunay syndrome). The macular network-like appearance of the tumor and coexisting ventral-caudal structural anomalies is analogous to the association of posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities association in the craniofacial region.

PHACE Syndrome with Intracerebral Hemangiomas, Heterotopia, and Endocrine Dysfunction

PHACE is an acronym to describe the association of posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta, cardiac defects, and eye abnormalities. More than 200 cases have been reported. The present report presents the cases of two female infants with PHACE syndrome, both of whom had additional congenital defects of subependymal gray matter heterotopia, craniofacial arterial anomalies, and pituitary dysfunction. One had an extensive segmental facial hemangioma with ipsilateral intracranial hemangiomas. The other had multiple cutaneous hemangiomas, but no segmental facial hemangioma. These two cases suggest a further expansion of the spectrum of PHACE to include other forms of disordered cerebral development and endocrine dysfunction.

A prospective study of PHACE syndrome in infantile hemangiomas: Demographic features, clinical findings, and complications

PHACE (OMIM no. 606519) is a neurocutaneous syndrome that refers to the association of large, plaque-like, "segmental" hemangiomas of the face, with one or more of the following anomalies: posterior fossa brain malformations, arterial cerebrovascular anomalies, cardiovascular anomalies, eye anomalies, and ventral developmental defects, specifically sternal defects and/or supraumbilical raphe. The etiology and pathogenesis of PHACE is unknown, and potential risk factors for the syndrome have not been systematically studied. The purpose of this study was thus to determine (1) the incidence of PHACE and associated anomalies among a large cohort of hemangioma patients, (2) whether certain demographic, prenatal or perinatal risk factors predispose infants to this syndrome, and (3) whether the cutaneous distribution of the hemangioma can be correlated to the types of anomalies present. We undertook a prospective, cohort study of 1,096 children with hemangiomas, 25 of whom met criteria for PHACE. These 25 patients represented 20% of infants with segmental facial hemangiomas. Compared to previous reports, our PHACE patients had a higher incidence of cerebrovascular and cardiovascular anomalies. Two developed acute arterial ischemic stroke during infancy, while two with cardiovascular anomalies showed documented evidence of normalization, suggesting that both progressive and regressive vascular phenomena may occur in this syndrome. Correlation to the anatomic location of the hemangioma appears to be helpful in determining which structural abnormalities might be present. A comparison of demographic and perinatal data between our PHACE cases and the hemangioma cohort overall showed no major differences, except a trend for PHACE infants to be of slighter higher gestational age and born to slightly older mothers. Eighty-eight percent were female, a finding which has been noted in multiple other reports. Further research is needed to determine possible etiologies, optimal evaluation, and outcomes.

A unique case of PHACES syndrome confirming the assumption that PHACES syndrome and the sternal malformation???vascular dysplasia association are part of the same spectrum of malformations

PHACES is an acronym for a rare neurocutaneous disorder including the following features: posterior fossa brain malformations; facial hemangiomas; arterial, cardiac, and eye anomalies; and sternal clefts and/or supraumbilical abdominal raphe. Facial hemangiomas are the hallmark of this syndrome. We report a patient with facial hemangiomas, sternal clefting and carotid abnormalities. She is another example of the combined existence of sternal clefting and carotid abnormalities in PHACES syndrome and even more unique since she does not have an aortic abnormality. This report emphasizes that many different combinations of features may be seen in PHACES syndrome.

PHACE syndrome: Association with Persistent Fetal Vasculature and coloboma-like iris defect

PHACE Syndrome is a neurocutaneous disease spectrum encompassing the following features: Posterior fossa brain malformations, large facial Hemangiomas, Arterial anomalies, Coarctation of the aorta and cardiac defects, and Eye abnormalities. We report the ocular and systemic findings, as well as the management course, of an infant who has all the characteristic features of PHACE syndrome and also describe what we believe to be the first reported case of this syndrome with Persistent Fetal Vasculature (PFV).

Death from cerebrovascular infarction in a patient with PHACES syndrome

Death from cerebrovascular infarction in a patient with PHACES syndrome