Wyburn-Mason Syndrome

Wyburn-Mason syndrome (WMS), also known as Bonnet-Dechaume-Blanc syndrome or retinoencephalofacial angiomatosis, is a rare nonhereditary congenital phakomatosis characterized by arteriovenous malformations (AVMs) of the retina, brain, and, in some cases, facial skin. Wyburn-Mason syndrome is usually unilateral and often asymptomatic.[1]

An example of a retinal AVM is shown in the image below.

The dilated and abnormal retinal vasculature characteristic of a retinal arteriovenous malformation.

Although these combined vascular abnormalities were recognized prior to the reports of Bonnet (1937)[2] and Wyburn-Mason (1943),[3] this syndrome is most frequently referred to as Wyburn­-Mason syndrome (WMS) to honor the initial author of the classic case series. Wyburn-Mason syndrome is a congenital, nonhereditary, sporadic disorder without sexual or racial predilection.[1] Other vascular malformations may be present elsewhere in the body, including facial skin. In contrast to other phakomatoses, Wyburn-Mason syndrome does not commonly cause cutaneous manifestations. However, WMS manifests as subtle facial nevi with angiomas around the trigeminal territory.

Although the exact etiology and risk factors associated with Wyburn-Mason syndrome are unknown, studies have suggested a role for genetic factors in the pathogenesis of retinal AVMs. Vascular dysgenesis of the embryological anterior plexus occurs early in the gestational period, characterized by variable alterations in capillary and arteriolar networks. Small AVMs may be asymptomatic and subtle, with only minor alterations within the capillary system. Alternatively, the classic large "bag­-of-­worms" racemose AVM lesions are characterized by direct artery­-to-­vein communication, without interposing capillary or arteriolar elements causing high blood flow.[1] The timing of the insult determines the embryonic tissue that is affected.

Frequency

United States

Wyburn-Mason syndrome is rare, and the precise incidence and prevalence are poorly defined. To date, fewer than 100 cases have been reported in the literature.

International

The worldwide incidence of Wyburn-Mason syndrome is also rare.

Race

Wyburn-Mason syndrome has no reported racial predilection, and there is no familial form of the syndrome.

Sex

Wyburn-Mason syndrome has no sexual predilection.

Age

Wyburn-Mason syndrome is a congenital disorder. Larger retinal AVMs that cause visual or neurologic impairment are generally diagnosed earlier in life, whereas smaller AVMs may remain asymptomatic and may not be diagnosed until later in life.

Prognosis depends on the extent and location of the lesions. Lesions may remain static, enlarge, or spontaneously regress.[1, 4, 5]

Neurologic symptoms of Wyburn-Mason syndrome (WMS) are extremely variable and depend on the size, location, and configuration of the central nervous system (CNS) AVM. Mental status or neuropsychiatric changes, headaches, seizures, stroke, hemiparesis, visual-field abnormalities (homonymous hemianopia), subarachnoid hemorrhage, intracerebral hemorrhages, increased intracranial pressure (papilledema), cranial neuropathies, and/or hydrocephalus may occur. Extracranial AVMs may manifest as potentially life-threatening oral hemorrhages or epistaxis.[4, 1]

Similarly, neuro­-ophthalmic signs and symptoms of Wyburn-Mason syndrome result from retinal or intracranial AVMs and are related to AVM size, extent, and location. Small AVMs may produce no visual symptoms, whereas larger AVMs may lead to profound vision loss. These signs and symptoms include retinal and vitreous hemorrhages, retinal detachment, venous occlusive disease (and secondary risk of rubeosis iridis and secondary glaucoma), optic disc edema, or optic atrophy. Intracranial AVMs may produce secondary neuro­-ophthalmic manifestations, including papilledema, pupillary changes, homonymous hemianopia, ptosis, proptosis, gaze paresis, cranial nerve palsies, strabismus, nystagmus, and, in childhood, superimposed amblyopia.[1, 6, 7, 8, 9, 10, 11]

Associated intracranial AVMs are more commonly found in patients with large, racemose retinal vascular anastomoses. CNS vascular lesions are typically ipsilateral to the involved eye, and they frequently involve the midbrain.[1, 6, 12, 13] In some cases, retinal lesions may result from an extension of an intracranial vessel malformation, extending anteriorly along the visual pathway, through the optic foramen, and along the optic nerve to the retina.

The ophthalmoscopic appearance of the retinal AVM may vary from small, abnormal vessel communications to extensive racemose involvement of the entire fundus. Retinal AVMs typically appear as dilated and tortuous retinal vessels extending from the optic disc to the retinal periphery, resembling a “bag of worms.” Also referred to as cirsoid aneurysm, arteriovenous aneurysm, arteriovenous communication of the retina, racemose hemangioma, and arteriovenous varix, these abnormal retinal vessels typically remain stable and do not demonstrate leakage on fluorescein angiography (FA). 

Archer et al classified retinal AVMs into 3 groups, as follows[14] :

• Group I is characterized by small arteriole-venule anastomoses, which may be subtle and difficult to clinically detect. These vessels are usually isolated to a sector or quadrant of the retina.

• Group II represents direct artery-to-vein communication without intervening capillary or arteriolar elements causing hyperdynamic flow through low-resistance veins. This group may represent an exaggerated form of the abnormalities included in group I and is likewise geographically segmented within the fundus. Complications can range from edema to hemorrhage.

• Group III includes malformations characterized by markedly convoluted, dilated, and tortuous retinal vessels extending throughout the entire fundus, making it virtually impossible to differentiate between arterial and venous components. These eyes usually are severely vision impaired, typically leading to earlier diagnosis in childhood. Patients in this group are at higher risk for systemic vascular involvement.

Theron and coworkers reviewed 80 cases of retinal vascular anastomoses and found that 30% of these patients also had CNS AVMs, a rate that is much lower than the 81% association reported by Wyburn-Mason.[15] Bech and Jensen believe that the original statistics from Wyburn-Mason are too high, noting that many of Wyburn-Mason's patients had no angiographic or pathologic evidence of intracranial vascular malformations.[16] The preponderance of patients with more advanced retinal lesions in the Wyburn-Mason study may have made associated CNS lesions more likely.

Intracranial and retinal AVMs occasionally are accompanied by vascular malformations in the facial skin, oronasopharnyx, orbit, lung, and bone. Facial lesions may involve the eyelids, cheeks, forehead, and other regions. Orbital involvement can present with proptosis, which may be pulsatile and have an accompanying bruit.

The etiology of Wyburn-Mason syndrome is unknown.

Retinal AVMs rarely may be complicated by vascular decompensation and ischemia-related changes.

Vision loss may occur secondary to photoreceptor damage, loss of the nerve fiber layer, or macular ischemia.[17, 18]  In addition, orbital or retro-orbital AVMs may induce optic neuropathy and progressive visual disturbances by compressing the optic nerve.[19]

Retinal ischemia eventually can lead to neovascular glaucoma.

Intracranial AVMs may be complicated by headaches, visual­-field abnormalities, and seizures. Patients also may experience irritability, cerebellar dysfunction, developmental delay, and/or Parinaud syndrome.[20] Lesions may rupture, resulting in significant morbidity.

AVMs within the mandible or the maxilla may result in excessive bleeding following dental procedures.

Wyburn-Mason syndrome usually is defined by the clinical findings.

Retinal AVMs typically are diagnosed ophthalmoscopically, but smaller lesions might require fluorescein angiography (FA). FA may demonstrate the abnormal retinal arteriovenous communications or the presence or absence of intervening capillary networks. Most AVMs are stable on FA and do not leak in late phases of the angiogram.

Ultrasonography and high-resolution imaging such as optical coherence tomography (OCT), spectral-domain optical coherence tomography (SD-OCT), and adaptive optics (AO) can be used to confirm the diagnosis and demonstrate structural changes over time in the nerve fiber layer, macula, and retina.[17, 21]

Intracranial AVMs are best diagnosed with cranial CT or magnetic resonance imaging (MRI) with and without contrast, computed tomography angiography (CTA) or magnetic resonance angiography (MRA), or catheter cerebral arteriography. In general, standard catheter angiography is considered the gold standard and can better demonstrate the size, location, and other key characteristics of the feeding arteries and draining veins.[22]

MRI provides additional important structural information on the extent of the AVM and any associated hemorrhage. Catheter arteriography offers a more comprehensive analysis of the exact angioarchitecture of the lesion.

Histologically, retinal AVMs demonstrate vessels to have a fibromuscular media of varying thickness and wide fibrohyaline adventitial coats. Arteries and veins may be indistinguishable and, in some cases, occupy the entire thickness of the retina.[23]

Options for treatment of unruptured intracranial AVMs include observation alone, radiation therapy with radiosurgery, endovascular embolization, surgical resection, or, in many cases, some combination of therapies. The risk for hemorrhage or other potentially life-threatening events from the AVM should be balanced against the risk of the specific treatments, the size, feeder, and draining pattern; the location of the lesion; and the expertise available at the individual institution.

Unlike intracranial AVMs, retinal AVMs do not usually bleed but can produce vitreous or retinal hemorrhages. Some patients are at a higher risk for loss of visual function through various mechanisms (eg, retinal vascular occlusions, retinal ischemia, retinal detachment, neovascular glaucoma).

Because of the stability of the retinal lesions, management by an ophthalmologist often is unnecessary in patients with Wyburn-Mason syndrome (WMS) beyond diagnosing the condition, obtaining intracranial imaging, organizing the appropriate systemic referrals, and performing routine and periodic ophthalmic examinations. Symptomatic medical treatment can be offered for neovascular glaucoma.[24, 25] However, recent reports have described success with intravitreal ranibizumab in the treatment of Wyburn-Mason syndrome with retinal artery macroaneurysm and exudation and intravitreal bevacizumab in the treatment of bilateral racemose hemangioma and retinal detachment.[26, 27]

Likewise, depending on individual findings, size, location, and course, many patients with cerebral AVM have been safely observed for long periods. Spontaneous resolution of these vascular lesions has been reported.

Scatter retinal photocoagulation may be indicated in instances of retinal ischemia following venous occlusive events. Likewise, pars plana vitrectomy for nonclearing vitreous hemorrhage and cyclodestructive procedures for neovascular glaucoma may be recommended.

As noted above, some intracranial AVMs may require multimodal therapy, including primary or adjunctive surgery.

Referral for neurologic evaluation is indicated when retinal AVMs are diagnosed.

Retinal consultation may be needed for treatment of intraocular lesions.

Neurologic, dermatologic, neurosurgical, radiation therapy, or neurointerventional consultations may be necessary.

Patients should be followed for progression clinically for intracranial and intraocular disease (vitreous hemorrhage, serous retinal detachment, cystoid macular edema, venous occlusions, neovascular glaucoma, neovascularization, choroidal infarction, and recently reported peripheral retinal ischemia), as well as radiographically for intracranial AVMs. Continued serial and possibly lifelong observation of patients with Wyburn-Mason syndrome is recommended.[28, 29]

Patients may require inpatient evaluation and treatment for intracranial lesions.