Wyburn-Mason Syndrome Research Articles

Current Treatment Approaches for Vascular Tumors of the Retina and Optic Disc

The vascular tumors of the retina and optic disc include retinal hemangioblastoma (capillary hemangioma), retinal cavernous hemangioma, retinal racemose hemangioma (Wyburn-Mason Syndrome) and retinal vasoproliferative tumor. Although retinal vascular tumors are not common, in some cases they can lead to diagnostic and therapeutic challenges. Sector laser photocoagulation, cryotherapy, transpupillary thermotherapy, photodynamic therapy, intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy, plaque radiotherapy, and endoresection procedures are commonly in the treatment of retinal hemangioblastoma. Cryotherapy, transpupillary thermotherapy, photodynamic therapy, intravitreal anti-VEGF therapy and dexamethasone implants, plaque radiotherapy, and endoresection methods can be applied in retinal vasoproliferative tumor. No treatment in usually necessary in retinal cavernous and racemous hemangiomas.

Pituitary macroadenoma causing vision loss in Wyburn-Mason syndrome: illustrative case.

Wyburn-Mason syndrome (WMS) is a neurocutaneous disorder consisting of vascular malformations of the brain, eye, and skin. These include characteristically high-flow intracranial and intraorbital arteriovenous malformations (AVMs) that present commonly with visual deterioration, headache, and hemiplegia. Complete removal of these lesions is challenging. Most patients are followed closely, and intervention occurs only in the setting of worsening symptoms secondary to AVM growth or hemorrhage. Here the authors present the first known case of a patient with WMS and a pituitary macroadenoma. A 62-year-old man with a 30-year history of WMS with right basal ganglia and orbital AVMs and right eye blindness presented for new-onset left-sided vision loss. A pituitary adenoma was identified compressing the optic chiasm and left optic nerve. Magnetic resonance imaging and digital subtraction angiography studies were obtained for surgical planning, and the patient underwent an endoscopic transnasal transsphenoidal resection, with significant postoperative vision improvement. Given the variable presentation and poor characterization of this rare syndrome, patients with WMS presenting with new symptoms must undergo evaluation for growth and hemorrhage of known AVMs, as well as new lesions. Further, in patients undergoing intracranial surgery, extensive preoperative imaging and planning are crucial for safe and successful procedures.

Retinal and intracranial arteriovenous malformations in Wyburn–Mason syndrome

A 12-year-old female presented with left exotropia for 1 year. The left eye fundus revealed dilation and tortuosity of the retinal arteries and veins consistent with group 3 retinal arteriovenous malformation (AVM; Fig. 1A). Fundus fluorescein angiography showed AVM filling without leakage but with a temporal nonperfusion area (Fig. 1B). Magnetic resonance angiogram of the head and cerebral angiography showed left orbital and suprasellar AVMs (Fig. 1C, D). The patient was diagnosed with Wyburn–Mason syndrome. No treatment was recommended for the intracranial AVMs because of the associated surgical risk to the perforators and the visual pathway.

Cerebrofacial vascular metameric syndrome is caused by somatic pathogenic variants in PIK3CA.

Disorganized morphogenesis of arteries, veins, capillaries, and lymphatic vessels results in vascular malformations. Most individuals with isolated vascular malformations have postzygotic (mosaic), activating pathogenic variants in a handful of oncogenes within the PI3K–RAS–MAPK pathway (Padia et al., Laryngoscope Investig Otolaryngol 4: 170–173 [2019]). Activating pathogenic variants in the gene PIK3CA, which encodes for the catalytic subunit of phosphatidylinositol 3-kinase, are present in both lymphatic and venous malformations as well as arteriovenous malformations in other complex disorders such as CLOVES syndrome (congenital, lipomatous, overgrowth, vascular malformations, epidermal anevi, scoliosis) (Luks et al., Pediatr Dev Pathol 16: 51 [2013]; Luks et al., J Pediatr 166: 1048–1054.e1–5 [2015]; Al-Olabi et al., J Clin Invest 128: 1496–1508 [2018]). These vascular malformations are part of the PIK3CA-related overgrowth spectrum, a spectrum of entities that have regionalized disordered growth due to the presence of tissue-restricted postzygotic PIK3CA pathogenic variants (Keppler-Noreuil et al., Am J Med Genet A 167A: 287–295 [2015]). Cerebrofacial vascular metameric syndrome (CVMS; also described as cerebrofacial arteriovenous metameric syndrome, Bonnet–Dechaume–Blanc syndrome, and Wyburn–Mason syndrome) is the association of retinal, facial, and cerebral vascular malformations (Bhattacharya et al., Interv Neuroradiol 7: 5–17 [2001]; Krings et al., Neuroimaging Clin N Am 17: 245–258 [2007]). The segmental distribution, the presence of tissue overgrowth, and the absence of familial recurrence are all consistent with CVMS being caused by a postzygotic mutation, which has been hypothesized by previous authors (Brinjiki et al., Am J Neuroradiol 39: 2103–2107 [2018]). However, the genetic cause of CVMS has not yet been described. Here, we present three individuals with CVMS and mosaic activating pathogenic variants within the gene PIK3CA. We propose that CVMS be recognized as part of the PIK3CA-related overgrowth spectrum, providing justification for future trials using pharmacologic PIK3CA inhibitors (e.g., alpelisib) for these difficult-to-treat patients.

Uncommon Presentation of Wyburn-Mason Syndrome in a Pediatric Patient

We report an uncommon presentation of Wyburn-Mason syndrome in a pediatric patient. An 11-year- old girl presenting with no light perception in her right eye. Examination revealed an exotropia and a large and tortuous retina vessel in the posterior part of her right eye. However, other examinations, including dermatological and neurological examination, are within normal limits. Magnetic Resonance Angiography (MRA) showed vascular malformation at the basal cistern that extends to the retrobulbar area. Therefore, a thorough examination of the eye and brain, including MRA, is mandatory in every case, even in pediatric with normal neurological examinations.

Bilateral Wyburn–Mason Syndrome Presenting with Macular Edema

The Wyburn-Mason or Bonnet-Dechaume-Blanc syndrome is a sporadic illness which is a type of phakomatosis, usually present as unilateral arteriovenous malformations(AVM), for the first defined by Magnus in 1874 as retinal AVM later in 1932 another description gave by Yates and Payne; as an AVMs of the retina and cerebral vasculature, while in 1937 Bonnet, Dechaume and Blanc defined as AVM involving facial, retinal and brain blood vessels, then in 1943 all literature revised by Wyburn-Mason to put together to his case reports, therefore, the name of Bonnet-Dechaume-Blanc syndrome given in France, but in English articles entitled as Wyburn-Mason syndrome. At that time, due to a deficiency in diagnostic imaging techniques, all the diagnosis were performed by clinical findings, operation, or autopsy. Usually, it is a unilateral disorder comprising of three distinct components: orbit, brain (ipsilateral to the retina) and face, in the face; the sensory region of the trigeminal nerve distribution involved, that takes the shape of naevi which might be wholly formed and illness, is complete, or the naevi might be faint or absent, the latter regarded as an incomplete disease but rarely a bilateral involvement encountered with an asymmetrical grade of malformation. The pathology starts in the early embryonic period, and if vascular dysgenesis encountered can lead to a wide range of neurocutaneous vascular defects in the cerebrum or ocular or both. When the disorder reaches the last stage, the AVM can compress the optic nerve causing impaired perfusion, ischemia eventually optic atrophy. Another explanation for visual loss is glaucoma as a result of elevated vascular pressure, neovascularization resulting from ischemia, which might lead to vitreous hemorrhage(5). Archer et al. staged the disease into three groups: Group 1 (AVM cannot be detected clinically). Group 2 (Clinically seen as edema and hemorrhage due to direct AVM, i.e., no capillary network between them). Group 3 (Clinically, it is impossible to distinguish arteries from veins due to severely dilated blood vessels all over retina). We present a 41-year-old male presented with a gradual decrease in his visual acuity in both eyes.

Wyburn Mason Syndrome: Novel presentation with Bilateral Retinal Arteriovenous malformation

A five-year-old girl with poor vision on examination and left eye esotropia was found to have bilateral intraorbital and unilateral intracranial arteriovenous malformation (AVM) and unilateral optic neuropathy. Magnetic Resonance Imaging with contrast revealed a small AVM involving the left ophthalmic artery and a large AVM involving the junction of anterior cerebral artery and anterior communicating artery. The simultaneous presence of retinal and intracranial AVM constitutes the Wyburn- Mason Syndrome (Retinoencephaloangiomatosis). Wyburn mason syndrome is associated with unilateral retinal racemose hemangioma with few cases with bilateral symmetrical involvement been reported in the literature. The present case has asymmetric bilateral retinal AVM and optic neuropathy, rare presentation of rare disease.

Arteriovenous Malformation associated with Wyburn Mason Syndrome

Arteriovenous Malformation associated with Wyburn Mason Syndrome

Image Gallery: Wyburn-Mason syndrome with a chronic wound

Image Gallery: Wyburn-Mason syndrome with a chronic wound

Malformação vascular retinoencefálica, síndrome de Wyburn-Mason

A síndrome de Wyburn-Mason constitui-se na presença de malformações arteriovenosas comumente localizadas na órbita, nos anexos oculares, na retina e no encéfalo, principalmente no mesencéfalo. Existem apenas 14 casos dessa rara doença congênita relatados na literatura, sendo apresentados os achados clínicos e radiológicos de um paciente de 31 anos de idade com esse diagnóstico desde os 7 anos. Ao exame neurológico apresenta amaurose à direita e visão normal à esquerda. Os exames de imagem evidenciaram malformação arteriovenosa envolvendo vasos orbitários direitos e espessamento do nervo óptico direito até a região opticoquiasmática. Em virtude da grande morbidade do tratamento cirúrgico, desde o momento do diagnóstico foi instituído tratamento conservador, tendo até o momento ocorrido evolução sem intercorrências.

Wyburn-Mason syndrome

In the article, a description of a clinical case of an extremely rare isolated ophthalmic form of the Wyburn-Mason syndrome is presented. Etiology, pathogenesis, clinical picture, and diagnostic criteria of this disease are also described.

A Conjunctival Vascular Malformation as a Rare Presenting Sign of Wyburn–Mason Syndrome

AbstractWyburn–Mason syndrome is a rare condition that is characterized by ipsilateral arteriovenous malformations affecting the eye, brain, and facial skin. A conjunctival vascular dilation can be a rare ocular presenting sign. We report a 6-year-old boy who attended the hospital because of the sudden appearance of a conjunctival vascular lesion in his right eye. Inspection of his facial skin showed a subtle discoloration along the right trigeminal nerve and a vascular structure of the conjunctiva. Fundoscopy showed dilated and tortuous retinal vessels. Brain magnetic resonance imaging (MRI) revealed a large arteriovenous malformation involving the thalamus and perimesencephalic area. Ophthalmologic and neuroradiologic findings were consistent with the diagnosis of Wyburn–Mason syndrome. The sudden emergence of a vascular malformation in the conjunctiva should alert the clinician to perform an ophthalmoscopy, and in our patient, this finding was the clue to diagnosis of Wyburn–Mason syndrome. Because of the association between retinal and intracranial arteriovenous malformations, an MRI of the brain is strongly recommended in all patients with ocular arteriovenous malformations.

Hemiretinal Vein Occlusion Secondary to Arteriovenous Malformation

Purpose: To describe an hemiretinal vein obstruction secondary to a congenital arteriovenous malformation. Methods: Case report of a young patient with retinal arteriovenous malformation and hemiretinal vein obstruction. Results: A 9-year-old girl had a grade II retinal arteriovenous communication in her left eye. She presented with sudden loss of vision in her left eye, and a diagnosis of a hemiretinal vein obstruction secondary to a congenital arteriovenous malformation complicated with macular edema, capillary nonperfusion and neovascularization of the retina was made. She received intravitreal bevacizumab and multiple sessions of laser photocoagulation. Magnetic resonance imaging of the brain was normal and disclosed no signs of Wyburn-Mason syndrome. During follow up the patient remained with stable visual acuity, involuted disease, and persistent macular edema. Conclusions: Awareness of retinal vascular obstruction associated with arteriovenous communication may aid early recognition, and prompt treatment of potential complications, such as retinal and iris neovascularization.

RETINAL ARTERIOVENOUS MALFORMATION

To describe a case of an isolated Group 3 retinal arteriovenous malformation (AVM). Observational case report. A 15-year-old girl with no significant medical history presented with no light perception vision in her right eye and gradually decreasing vision in her left eye over several years. She was found to have a large AVM in the posterior pole of the right eye with associated perivascular sheathing in the periphery. Her left eye seemed totally unremarkable. Neuroimaging revealed no intracranial or intraorbital abnormalities. A diagnosis of isolated Group 3 retinal AVM was made. Retinal AVMs are congenital, nonhereditary, and sporadic vascular anomalies that develop in the posterior pole. A number of patients with this finding can have coexisting AVMs in the brain, mandible, skin, or orbit, which comprises the Wyburn-Mason syndrome. Because of these systemic associations, neuroimaging should always be considered when a retinal AVM is seen. Severe vision loss can occur from these AVMs secondary to a number of ocular complications, including central retinal vein occlusions.

Wyburn-Mason syndrome – A rare preventable cause of CV stroke in young.

Wyburn-Mason syndrome – A rare preventable cause of CV stroke in young.

A Case of Wyburn-Mason Syndrome with Facial Nevus Flammeus and the Associated Optical Coherence Tomography Findings

Purpose: To describe a case of Wyburn-Mason Syndrome, which is a rare phakomatosis, and its associated optical coherence tomography findings. Case summary: A 5-year-old boy was referred to our clinic for decreased vision in his right eye. He had nevus flammeus on his right forehead, upper eyelid, and cheek. His best corrected visual acuity was hand motion in the right eye, in which a relative afferent pupillary defect was noted. Fundus examination of the right eye showed marked dilation and tortuosity of retinal vessels, which could not be discriminated between arteries and veins on the posterior pole. Optical coherence tomography showed multiple large intraretinal vessels without involvement of the internal limiting membrane. Cerebral angiography revealed arteriovenous malformations (AVMs) and feeder vessels from the internal carotid artery to the ophthalmic artery, extending to the ethmoidal artery in the nasal cavity. Conclusions: Wyburn-Mason syndrome is a rare phakomatoses and shows unique retinal AVM. Misdiagnosis or undertreatment of Wyburn-Mason syndrome can lead to serious complications. Patients with facial nevus flammeus should undergo thorough ocular examinations to rule out this disorder. Optical coherence tomography is a useful method for understanding structural features of retinal vascular malformations in Wyburn-Mason syndrome. J Korean Ophthalmol Soc 2016;57(8):1333-1338

Seizures Are Not a Prevalent Feature of Wyburn-Mason Syndrome

Wyburn-Mason syndrome (WMS) is a widely recognized neurocutaneous syndrome in which the unilateral anterior venous malformation in its complete form is associated with eye, brain, and skin involvement. The term WMS also includes the incomplete form in which the patients show unilateral anterior venous malformation as a single anomaly not associated with other districts involvement. Neurologic complications are almost constantly reported in this syndrome. The aim of this report is to describe the neurologic course of two patients affected by the complete form of this very rare syndrome offering particular remarks whether convulsive episodes or epilepsy are leading features of this disorder. Based on the experience registered in the long follow-up in the present patients and in those reported in the literature, seizures and convulsive episodes are uncommon in WMS and, when present, mainly occur in consequence of acute or chronic disruptive events of the arteriovenous malformations.

Mosaic Neurocutaneous Disorders and Their Causes

Neurocutaneous disorders are a heterogeneous group of conditions (mainly) affecting the skin [with pigmentary/vascular abnormalities and/or cutaneous tumours] and the central and peripheral nervous system [with congenital abnormalities and/or tumours]. In a number of such disorders, the skin abnormalities can assume a mosaic patterning (usually arranged in archetypical patterns). Alternating segments of affected and unaffected skin or segmentally arranged patterns of abnormal skin often mirror similar phenomena occurring in extra-cutaneous organs/tissues [eg, eye, bone, heart/vessels, lung, kidney and gut]. In some neurocutaneous syndromes the abnormal mosaic patterning involve mainly the skin and the nervous system configuring a (true) mosaic neurocutaneous disorder; or an ordinary trait of a neurocutaneous disorder is sometimes superimposed by a pronounced linear or otherwise segmental involvement; or, lastly, a neurocutaneous disorder can occur solely in a mosaic pattern. Recently, the molecular genetic and cellular bases of an increasing number of neurocutaneous disorders have been unravelled, shedding light on the interplays between common intra- and extra-neuronal signalling pathways encompassing receptor-protein and protein-to-protein cascades (eg, RAS, MAPK, mTOR, PI3K/AKT and GNAQ pathways), which are often responsible of the mosaic distribution of cutaneous and extra-cutaneous features. In this article we will focus on the well known, and less defined mosaic neurocutaneous phenotypes and their related molecular/genetic bases, including the mosaic neurofibromatoses and their related forms (ie, spinal neurofibromatosis and schwannomatosis); Legius syndrome; segmental arrangements in tuberous sclerosis; Sturge-Weber and Klippel-Trenaunay syndromes; microcephaly/megalencephaly-capillary malformation; blue rubber bleb nevus syndrome; Wyburn-Mason syndrome; mixed vascular nevus syndrome; PHACE syndrome; Incontinentia pigmenti; pigmentary mosaicism of the Ito type; neurocutaneous melanosis; cutis tricolor; speckled lentiginous syndrome; epidermal nevus syndromes; Becker's nevus syndrome; phacomatosis pigmentovascularis and pigmentokeratotica; Proteus syndrome; and encephalocraniocutaneous lipomatosis.

Chapter 12 - PHACE(S) syndrome

PHACE(S) syndrome is a neurocutaneous disorder of unknown etiology. The acronym refers to the commonest features of PHACE: posterior fossa malformations, large facial hemangiomas, cerebral arterial anomalies, cardiovascular anomalies, and eye anomalies. When ventral developmental defects such as sternal clefting or supraumbilical raphe occur, the PHACES acronym may be used. The hallmark feature of PHACE is the presence of one or more large facial infantile hemangiomas that occupy at least one facial segment. Infantile hemangiomas differ from the capillary malformation (port wine stain) of Sturge-Weber syndrome, and the arteriovenous malformation of Wyburn-Mason syndrome, distinguishing PHACE syndrome from other neurocutaneous disorders with red birthmarks. The true incidence of PHACE has not yet been established. Girls are more commonly affected than boys. Cerebral vascular anomalies are probably the most common extracutaneous feature. Given that several organ systems are involved, a multidisciplinary approach to disease surveillance and treatment is advised.

La mélanose neurocutanée et les nævus mélanocytaires congénitaux multiples sont liés à des mutations post-zygotiques du gène N-ras

Neurocutaneous disorders are a heterogeneous group of conditions (mainly) affecting the skin [with pigmentary/vascular abnormalities and/or cutaneous tumours] and the central and peripheral nervous system [with congenital abnormalities and/or tumours]. In a number of such disorders, the skin abnormalities can assume a mosaic patterning (usually arranged in archetypical patterns). Alternating segments of affected and unaffected skin or segmentally arranged patterns of abnormal skin often mirror similar phenomena occurring in extra-cutaneous organs/tissues [eg, eye, bone, heart/vessels, lung, kidney and gut]. In some neurocutaneous syndromes the abnormal mosaic patterning involve mainly the skin and the nervous system configuring a (true) mosaic neurocutaneous disorder; or an ordinary trait of a neurocutaneous disorder is sometimes superimposed by a pronounced linear or otherwise segmental involvement; or, lastly, a neurocutaneous disorder can occur solely in a mosaic pattern. Recently, the molecular genetic and cellular bases of an increasing number of neurocutaneous disorders have been unravelled, shedding light on the interplays between common intra- and extra-neuronal signalling pathways encompassing receptor-protein and protein-to-protein cascades (eg, RAS, MAPK, mTOR, PI3K/AKT and GNAQ pathways), which are often responsible of the mosaic distribution of cutaneous and extra-cutaneous features. In this article we will focus on the well known, and less defined mosaic neurocutaneous phenotypes and their related molecular/genetic bases, including the mosaic neurofibromatoses and their related forms (ie, spinal neurofibromatosis and schwannomatosis); Legius syndrome; segmental arrangements in tuberous sclerosis; Sturge-Weber and Klippel-Trenaunay syndromes; microcephaly/megalencephaly-capillary malformation; blue rubber bleb nevus syndrome; Wyburn-Mason syndrome; mixed vascular nevus syndrome; PHACE syndrome; Incontinentia pigmenti; pigmentary mosaicism of the Ito type; neurocutaneous melanosis; cutis tricolor; speckled lentiginous syndrome; epidermal nevus syndromes; Becker’s nevus syndrome; phacomatosis pigmentovascularis and pigmentokeratotica; Proteus syndrome; and encephalocraniocutaneous lipomatosis.