Diagnosis Of PHACE Syndrome Research Articles

PHACE syndrome in a Nigerian newborn: case report and literature review

Background: PHACE syndrome is a rare neurocutaneous disorder characterised by large cervicofacial haemangiomas and associated anomalies of the brain, cerebro-vasculature, aorta, heart, and eyes. This case report describes the clinical presentation, management, and literature review of the disorder. Case Report: An hour-old term baby girl presented with a large midline facial haemangioma, microcephaly with absent anterior fontanelle, right microphthalmia, and absent left eye. She also had multiple seizures. There were telangiectatic areas all over the extensor surfaces of both the upper and lower limbs. There was a wide disparity between the heart rate and pulse rate with a radio-radial delay. The respiratory and digestive systems were essentially stable. Transtemporal and trans-posterior fontanelles USS showed hydrocephalus in the lateral ventricles. A brain CT scan showed intracranial defects in the posterior fossa. Based on the haemangioma, posterior fossa brain malformation, cardiovascular, ocular, and signs of cerebrovascular anomalies, the diagnosis of PHACE syndrome was made. A multi-disciplinary treatment approach was thimplemented. However, the patient died on the 29 day of life. Conclusion: PHACE syndrome is a rare condition that has only been described three hundred times in medical literature. The Multidisciplinary approach to management can be challenging in low-resource settings. However, knowledge of the features is crucial for the diagnosis and proper management of PHACE syndrome patients

Abstract TP408: Risk Factors for Clinical and Radiographic Progression in Pediatric Moyamoya

Objective: To compare clinical and radiographic evolution of moyamoya disease (MMD) and moyamoya syndrome (MMS). Method: We conducted a retrospective review of a prospectively enrolled cohort of children with moyamoya followed from 2003 to 2018. Patients with a final diagnosis of PHACE syndrome and transient cerebral arteriopathy were excluded. Demographic, clinical and radiographic (MRI) characteristics at diagnosis were obtained. Evidence of clinical evolution (stroke, TIA) or radiographic progression were assessed on subsequent clinical visits and neuroimaging, respectively. We compared the frequency and time to clinical and radiographic progression prior to revascularization surgery between MMD and MMS (including specific etiologies, namely neurofibromatosis [NF1] and sickle cell disease [SCD]). Comparisons were conducted using independent t or chi-square tests, as appropriate. Results: Ninety-three patients were identified, of whom 37 had MMD and 56 had MMS (20 NF1, 20 SCD and 16 others etiologies). The median age at presentation was 8.31 years (IQR 5.03-10.87) and the median follow up time was 5 years ( IQR 2-8). MMD were at greater risk of a recurrent ischemic event (52% MMD vs 42% MMS, p=0.049), but no difference was noted between MMD, NF1 and SCD. The risk of ischemic event recurrence was significantly higher among patients who presented with TIA at diagnosis (79.26% vs 21%, p <0.0001), an advanced Suzuki stage (59% with Suzuki 3-6 vs 28% Suzuki with 1-3, p= 0.009) and bilateral moyamoya (47% vs 21.95% with unilateral, p=0.012). No difference was noted between groups regarding the median time to radiographic progression. Radiographic progression was more likely among younger children (50% if less 10 years vs 21% if more than 10 years, p= 0.0085) and children presenting with TIA (53% vs 34%, p=0.038). Conclusions: TIA at presentation, advance Suzuki stage, and bilateral disease conferred greater ischemic risk among children with moyamoya. Vasculopathy progression was more likely among young patients and those with TIA at presentation.

Phace синдром у дітей: поєднання сегментарних гемангіом обличчя і розщеплення груднини

Мета роботи: визначення поширеності PHACE синдрому у дітей з інфантильними гемангіомами (ІГ), оцінка результатів лікування пропранололом та встановлення необхідності проведення додаткових хірургічних втручання.Матеріали і методи. У дослідження включено 27 дітей з ІГ в ділянці голови і шиї, які знаходилися на стаціонарному лікуванні в НДСЛ «ОХМАТДИТ» від грудня 2010 до березня 2017 року. Для встановлення діагнозу використовували УЗД, МРТ, КТ з контрастуванням, ехокардіографію, пацієнтам проводили також офтальмологічне обстеження.Результати та обговорення. Діагноз PHACE синдрому встановлено у 4 (14,81%) пацієнтів серед 27 дітей з ІГ ділянки обличчя і шиї діаметром понад 5 см. PHACE синдром діагностували за наступними критеріями: наявність сегментарних ІГ обличчя (n=4), в тому числі сітчаста гемангіома (n=1), розщеплення груднини (n=3), патологія задньої черепної ямки (n=1), коарктація аорти (n=1), правобічна дуга аорти (n=1), надпупковий шов (n=1). Усі пацієнти були жіночої статі. Поширення ІГ на ділянку дихальних шляхів з порушенням їх прохідності діагностовано у 3 (75%) випадків з PHACE синдромом. Для лікування ІГ використовували консервативну терапію: пропранолол – неселективний бета-блокатор – в дозі 2 мг/кг/добу. Консервативна терапія ІГ у дітей з PHACE синдромом є ефективною та безпечною, однак характеризується відносно більшою тривалістю. Операційне лікування з приводу розщеплення груднини виконано у 3 пацієнтів, у двох застосована первинна рання корекція вади у віці 2 і 4 місяці. В усіх пацієнтів досягнуто доброго функціонального і косметичного результату після хірургічного лікування.

P24.07: Posterior fossa imaging features enabling diagnosis of PHACE syndrome in utero

P24.07: Posterior fossa imaging features enabling diagnosis of PHACE syndrome <i>in utero</i>

Neurodevelopmental Outcomes in Children with PHACE Syndrome

Practitioners who work with children with posterior fossa, facial hemangiomas, arterial anomalies, cardiovascular anomalies, and abnormalities of the eye (PHACE) syndrome need information about neurodevelopmental outcomes to provide appropriate anticipatory guidance and education for parents. This study aimed to determine the neurodevelopmental outcomes in children with PHACE syndrome and identify which children may be at greatest risk for delays. Children with a diagnosis of PHACE syndrome (ages 4-18 yrs) were recruited from the PHACE Syndrome International Clinical Registry and Genetic Repository. Participants (n = 25) underwent a neurodevelopmental evaluation at a children's hospital tertiary care referral center between 2009 and 2013. Children completed standardized neurocognitive tests assessing multiple domains. Parents completed standardized questionnaires assessing behavioral and emotional functioning. Results were analyzed according to cohort and individual subject. Mean scores for the cohort did not differ significantly from test norms in most domains. The only subtest that the cohort scored lower on than test norms was Word Structure, a language task. Forty-four percent of the sample scored within the normal range in all domains, 28% had one score in the at-risk range (1-2 standard deviations [SDs] below the mean), 12% had two or more scores in the at-risk range, and 16% had at least one score in the impaired range (>2 SDs below the mean). Although most children in this cohort of patients with PHACE syndrome did not have significant neurodevelopmental deficits, a subset of patients had delays in multiple areas. Practitioners who work with these children should routinely ask about neurocognitive and developmental skills. Children with more severe phenotypes should be referred for appropriate evaluations and intervention services.

PP04.9 – 2616: Stroke and progressive cerebral vasculopathy in PHACE syndrome

Objective To contribute to current understanding of PHACE syndrome which is limited to case series reports in literature. Methods We present on outcome of a patient who suffered a single cerebrovascular event in infancy and had evidence of progressive cerebral vasculopathy over time. Results A female patient born at term had prominent plaque haemangioma (involving face, neck, trachea, mediastinum) and staphyloma of the left eye associated with amblyopia. She required tracheostomy in infancy and subsequent tracheal reconstruction. At seven months she presented with right focal seizure, mild ipsilateral hemiparesis, and large left middle cerebral artery infarct on MRI. She then developed recurrent headaches and repeat MRI/MRA at 5 years showed absent distal left internal carotid artery (ICA) and right supraclinoid ICA, presence of both occlusive and ectatic vascular disease in the intracranial circulation, and extensive collaterals. A diagnosis of PHACE syndrome (posterior fossa malformations, haemangiomas, arterial anomalies, cardiac defects, eye abnormalities, sternal cleft and supra-umbilical raphe syndrome) was made on the basis of facial haemangioma and classical cerebral vasculopathy. She did not have sternal cleft or supra-umbilical raphe. Serial echocardiography was unremarkable. Over the subsequent 10 years, she has continued to have recurrent headaches associated with normal development. MRI has shown progression of the aneurysmal segments of the left posterior communicating artery and surgical revascularisation is being considered. Conclusion The majority of PHACE cases with arterial ischaemic stroke (AIS) have aplasia, hypoplasia and/or occlusion of a major cervical or cerebral artery. As in this patient the infarcted area often correlates with the site of ICA vasculopathy. Though the role of cerebral vasculopathy in causation of AIS is unclear, the three mechanisms proposed are dysplastic or stenotic anomaly, ischaemia and cardioembolism. Outcome correlates with progressive vasculopathy, which may lead to infarction and aneurysmal rupture. To contribute to current understanding of PHACE syndrome which is limited to case series reports in literature. We present on outcome of a patient who suffered a single cerebrovascular event in infancy and had evidence of progressive cerebral vasculopathy over time. A female patient born at term had prominent plaque haemangioma (involving face, neck, trachea, mediastinum) and staphyloma of the left eye associated with amblyopia. She required tracheostomy in infancy and subsequent tracheal reconstruction. At seven months she presented with right focal seizure, mild ipsilateral hemiparesis, and large left middle cerebral artery infarct on MRI. She then developed recurrent headaches and repeat MRI/MRA at 5 years showed absent distal left internal carotid artery (ICA) and right supraclinoid ICA, presence of both occlusive and ectatic vascular disease in the intracranial circulation, and extensive collaterals. A diagnosis of PHACE syndrome (posterior fossa malformations, haemangiomas, arterial anomalies, cardiac defects, eye abnormalities, sternal cleft and supra-umbilical raphe syndrome) was made on the basis of facial haemangioma and classical cerebral vasculopathy. She did not have sternal cleft or supra-umbilical raphe. Serial echocardiography was unremarkable. Over the subsequent 10 years, she has continued to have recurrent headaches associated with normal development. MRI has shown progression of the aneurysmal segments of the left posterior communicating artery and surgical revascularisation is being considered. The majority of PHACE cases with arterial ischaemic stroke (AIS) have aplasia, hypoplasia and/or occlusion of a major cervical or cerebral artery. As in this patient the infarcted area often correlates with the site of ICA vasculopathy. Though the role of cerebral vasculopathy in causation of AIS is unclear, the three mechanisms proposed are dysplastic or stenotic anomaly, ischaemia and cardioembolism. Outcome correlates with progressive vasculopathy, which may lead to infarction and aneurysmal rupture.

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.

Adult Presentation of PHACES Syndrome

A significant percentage of children with hemangiomas may have PHACES syndrome which refers to the association of posterior fossa malformations, facial hemangiomas, arterial cerebrovascular abnormalities, cardiovascular anomalies, eye abnormalities and ventral defects like sternal clefting or supraumbilical raphe. A variety of factors have led to under diagnosis of PHACES syndrome in the past including lack of awareness and limited imaging modalities. Also, patients with PHACES syndrome with arterial cerebrovascular abnormalities can present with acute ischemic stroke. However, these patients usually present before one year of age. We describe a 29-year-old woman with no history of cerebrovascular disease who initially presented with symptoms of a stroke and was subsequently diagnosed to have PHACES syndrome exhibiting an array of multiple unusual imaging findings. We also discuss the current literature and recommendations about PHACES syndrome.

Risk for PHACE Syndrome in Infants With Large Facial Hemangiomas

This study was conducted to determine the prevalence of posterior fossae of the brain, arterial anomalies, cardiac anomalies, and eye anomalies (PHACE) in infants with large facial hemangiomas. The extracutaneous manifestations of PHACE may be associated with significant morbidity, and the prevalence of PHACE in patients with facial hemangiomas has not previously been reported. A multicenter prospective study was conducted with 108 infants who had large facial hemangiomas and were systematically evaluated for manifestations of PHACE. The prevalence of PHACE and its extracutaneous manifestations in this cohort was calculated. The relationship between hemangioma distribution and the manifestations of PHACE was analyzed. Thirty-three (31%) of 108 had PHACE. Thirty of the 33 patients with PHACE had >1 extracutaneous finding. The risk for PHACE syndrome was higher in infants with larger hemangiomas and in those with hemangiomas that encompassed >1 facial segment. The most common extracutaneous anomalies observed in infants with PHACE were of the arteries of the cerebrovasculature (91%) and cardiac anomalies (67%). Upper face (frontotemporal and frontonasal) hemangiomas were commonly observed in infants with PHACE; isolated maxillary hemangiomas were rarely associated with PHACE. In infants with large facial hemangiomas, one-third have extracutaneous manifestations consistent with the diagnosis of PHACE syndrome, most commonly cerebrovascular and cardiovascular anomalies. The high prevalence of arterial anomalies in this cohort has implications for clinical management and future research regarding the pathophysiology of PHACE.

An Infant With a Facial Hemangioma and More

A patient with a neurocutaneous disorder characterized by large facial infantile hemangiomas and associated abnormalities of the brain, cerebral vasculature, eyes, aorta, heart, and chest wall is presented. All children presenting with segmental infantile hemangiomas should undergo a complete diagnostic workup. We encourage a multidisciplinary clinical approach that minimally includes evaluations by dermatology, cardiology, ophthalmology, radiology, and neurology. The diagnosis of PHACES syndrome is confirmed in a child presenting with the characteristic facial hemangioma and at least 1 associated extracutaneous feature.

An Infant With a Segmental Hemangioma: Sturge-Weber?

A 6-week-old infant was referred for possible Sturge-Weber syndrome. The patient had a segmental hemangioma primarily involving the left eye. Subsequent evaluation suggested the diagnosis of PHACES syndrome, which is discussed. The risks to vision presented by the orbital involvement of the hemangioma should be noted.

Giant fusiform aneurysm in an adolescent with PHACES syndrome treated with a high-flow external carotid artery–M3bypass

The acronym PHACES describes a rare neurocutaneous syndrome that comprises posterior fossa malformations, facial hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, eye abnormalities, and sternal defects. Facial hemangiomas constitute the hallmark of this disorder. Giant intracranial aneurysms have not been previously reported in the literature as manifestations of PHACES syndrome and can present difficult therapeutic challenges. The authors describe a unique case of a 13-year-old adolescent boy with an incomplete phenotypic expression of PHACES syndrome who harbored diffuse cerebral angiodysplasia and a giant fusiform internal carotid artery (ICA) aneurysm extending from the distal cavernous segment to the supraclinoid segment. The aneurysm was successfully treated with a high-flow saphenous vein graft bypass from the external carotid artery to the distal middle cerebral artery followed by proximal ICA occlusion. This case represents a unique vascular manifestation of PHACES syndrome that required a complex management strategy. The authors review the literature on this rare disorder and emphasize the importance of considering the diagnosis of PHACES syndrome in child with a facial hemangioma.

Small facial haemangioma and supraumbilical raphe-a forme fruste of PHACES syndrome?

We report two female infants with congenital midline supraumbilical raphes who subsequently developed haemangiomas on the lower lip and gingiva within the first 2 months of life. One was found to have a subglottic haemangioma during laryngoscopy. The infants were otherwise well and had normal chest X-ray, echocardiogram, cranial ultrasound, magnetic resonance imaging/angiography (head, neck, chest) and ophthalmological examination. Both received oral prednisolone 1-2 mg kg(-1) daily and four sessions of flashlamp pulsed-dye laser therapy to the lip lesions, with significant improvement. The initial presentation of these two infants with supraumbilical raphes, who were otherwise healthy and without other cutaneous stigmata, suggested the diagnosis of isolated congenital sternal malformation. However, lower lip and gingival haemangiomas developed 4-6 weeks later, consistent with the diagnosis of PHACES syndrome. Children with sternal malformation and haemangioma may also have intracranial and/or cardiovascular anomalies. All previously reported patients were females who had either craniofacial and/or multiple haemangiomas. We propose guidelines for the evaluation and management of a neonate presenting with a sternal fusion defect at birth.