artery and the vein; Group II lacks an intervening capillary between the major vessels and there is direct arteriovenous anastomoses; Group III is the most severe and has dilated and tortuous vessels with no distinction between the artery and vein [195]. Group I patients are usually asymptomatic and do not have a tendency for intracranial involvement. Group III patients have the highest risk for intracranial and periorbital AVM. Typically, the AVMs do not bleed or cause exudation but they can lead to retinal ischemia [196, 197].

7.6.5  Genetics

Wyburn–Mason syndrome is a nonhereditary sporadic disorder.

7.6.6  Pathophysiology

Wyburn–Mason syndrome results from a developmental abnormality that affects the primitive vascular mesoderm shared by the developing optic cup and the anterior neural tube. Disturbance of these developing tissues prior to 7 weeks of gestation causes persistence of primitive vascular tissue of the eye and the mesencephalon. Disturbances after the seventh week typically affect only one of the two structures [198]. The majority of patients present with unilateral lesions. However, bilateral cases have been reported [199–201].

7.6.8  Signs and Symptoms

7.6.8.1  Ocular Findings

Retinal Arteriovenous Malformation

Mild cases of retinal AVMs, such as those in Group I, are mostly noted incidentally on a routine eye examination. Group II and Group III AVMs usually lead to visual loss and the diagnosis is made when an eye is evaluated for unexplained visual loss. The ophthalmoscopic appearance of retinal AVM is striking with dilated and tortuous retinal vessels extending from the optic disk to the retinal periphery (Fig. 7.10). In ­contrast to VHL in which the lesion can be located ­anywhere in the retina, AVMs of Wyburn-Mason syndrome tend to affect the posterior pole. These lesions are associated with high flow with potential for decompensation. Vasculature occlusion results from thrombosis or compression of the retinal vein by an expanding AVM.

Similar AVMs within the orbit, with or without retinal changes in the setting of Wyburn-Mason Syndrome have also been reported [198]. The intracranial AVMs in the chiasmal region can lead to neuro-ophthalmic presentation [201]. The intracranial AVM presents with signs and symptoms of acute cerebral or subarachnoid hemorrhage such as severe headache, nuchal rigidity, and loss of consciousness.

7.6.7  Natural History and Prognosis

The diagnosis of Wyburn–Mason syndrome is often made late in childhood because there are no prominent external features. The retinal vascular anomalies may alter in configuration over many years and sometime lead to vascular occlusions and retinal ischemia with the development of neovascular glaucoma [196, 197, 202]. The intracranial hemangioma is most often located in the midbrain and becomes symptomatic by the second or third decade, presenting as cerebral hemorrhage.

Fig. 7.10  Arteriovenous malformation (AVM) of Wyburn-Mason syndrome. Retinal AVM with dilation and tortuosity of retinal vessels. Reproduced with permission from: Singh et al. [232]