Cerebrofacial arteriovenous metameric syndrome (ORPHA:141189)
A group of rare, nonhereditary, complex cerebrofacial vascular malformation characterized by multiple ipsilateral arteriovenous malformations (AVMs) with a metameric distribution, affecting various territories of the face with corresponding areas of the brain. The spectrum is highly variable with three types described according to lesion distribution: CAMS 1 derives from the medial prosencephalon with concurrent involvement of hypothalamus, nose, forehead; CAMS 2 arises from the lateral prosencephalon and involves basal ganglia, optic nerve and retina and maxillo-facial region; CAMS 3 derives from the rhombencephalon and involves cerebellum and mandible.
Epidemiology
Fewer than 100 cases have been reported in the literature to date. The sex ratio is even.
Clinical description
Cerebrofacial arteriovenous metameric syndrome (CAMS) typically presents before the third decade of life. The spectrum is highly variable and symptoms will depend on the lesion's location. The neurological symptoms vary according to the affected cerebral area (hemiparesis, hemorrhage, visual field defect ...) as the maxilla-facial symptoms vary according to the facial extension (nosebleed, maxilla-facial deformation and AVMs, hemorrhage). Focal distribution of the lesions can be seen in partial spectrum of the disease.
Etiology
While the etiology and risk factors are unknown, a somatic mutation in the neural crest prior to migration is thought to produce the vascular lesions. Recent data suggest the role of somatic mutation of the RAS-MAPK signaling pathway in the pathogenesis of cerebrofacial AVMs.
Diagnostic methods
The diagnosis is made on clinical and radiological exam; partial manifestations of the syndrome does not exclude diagnosis. Retinal AVMs are usually diagnosed by ophthalmoscopy although fluorescein angiography may be required to demonstrate smaller lesions. Intracranial lesions can be diagnosed with magnetic resonance imaging/angiography (MRI/MRA), computed tomography and digital subtraction angiography.
Differential diagnosis
Differential diagnosis includes has to be made with other types of cerebrofacial vascular metameric syndromes like Sturge-Weber syndromes that affect the venous circulations in a metameric way without any shunt, or Von Hippel-Lindau disease that corresponds to vascular tumors as hemangioblastoma that can be seen in the retina or central nervous system. Lower metameric distribution compared to CAMS will correspond to spinal arteriovenous metameric syndromes (SAMS 1-31, or Cobb syndrome).
Genetic counseling
The disease is sporadic; no familial cases have been identified.
Management and treatment
Management depends on clinical presentation and can be conservative for asymptomatic or pauci-symptomatic lesions. Treatment is typically symptomatic and may include surgery, embolization or radiosurgery. Usually, given the lesions extension, complete curative treatment is not achievable. Medical antiangiogenic treatments are under evaluation.
Prognosis
Prognosis depends on the location and progression of AVMs, and while some patients may remain asymptomatic others will experience visual and/or neurological problems, as cosmetic sequelae related to the soft tissue AVM.

                            Last update: 
                            July 2024


                            - Expert reviewer(s): 
                            Dr Julien COULIE  - Dr Georges RODESCH | VASCERN* - Dr Stanislas SMAJDA | VASCERN*


                                * European Reference Network