PHACE syndrome (ORPHA:42775)
PHACE is an acronym used to describe a syndrome characterised by the association of Posterior fossa brain malformations, large facial Haemangiomas, anatomical anomalies of the cerebral Arteries, aortic coarctation and other Cardiac anomalies, and Eye abnormalities. Sternal anomalies are also sometimes present, and in these cases the syndrome is referred to as PHACES. Two additional manifestations have recently been added to the clinical spectrum of PHACE syndrome: stenosis of the vessels at the base of the skull and segmental longitudinal dilations of the internal carotid artery.
Epidemiology
This association of manifestations is rare and less than 100 cases have been reported in the literature so far. The syndrome is much more common in females than in males (8:1).
Clinical description
Newborns and infants are affected. Expression of the complete clinical picture of PHACE syndrome is extremely rare and most patients display only a partial phenotype (or incomplete clinical spectrum). The posterior fossa malformations include cerebellar hypoplasia, arachnoid cysts, cortical dysgenesis and Dandy-Walker malformation. The capillary haemangiomas have the same morphological, clinical and evolutive characteristics as those of sporadic benign haemangiomas. Intracranial and subarachnoid lesions may occur concurrently, with the intracranial lesions evolving in the same manner as the maxillofacial or cervical haemangiomas. Two types of arterial anomalies have been described: persistence of embryological arteries and agenesis of the carotid or vertebral artery. These anatomical arrangements allow normal cerebral function but limit the capacity for collateral circulation in case of an associated occlusive or stenotic lesion. The ophthalmological anomalies include glaucoma, coloboma, microphthalmia, cryptophthalmia and optic nerve hypoplasia. In most cases, the vascular lesions are uni- and homolateral, indicating that PHACE syndrome is a member of the group of cerebrofacial syndromes with involvement of several adjacent segments of the neural crest. Sternal anomalies resulting from ventral developmental defects are rare and include sternal clefts and/or malformations of the supraumbilical raphe. Progressive stenotic lesions of the intracerebral arteries (which are usually unilateral) are localised to the anterior or posterior divisions of the internal carotid artery. They result from concentric proliferation of the vascular wall causing a progressive reduction in the size of the lumen. Thickening of the vascular wall is also responsible for elongation of the internal carotid artery segments. The resulting neurological symptoms are variable, depending on the size and associated territory of the occluded vessels. Other manifestations such as headaches or delayed psychomotor development may also be caused by the same ischemic aetiology.
Etiology
The aetiology of the syndrome is unknown.
Diagnostic methods
Diagnosis can be confirmed by CT scan, MRI and cardiopulmonary investigations. Angiography is not performed systematically. Early diagnosis and treatment decreases the number and lessens the severity of complications.
Genetic counseling
The female predominance indicates male-lethal X-linked dominant transmission.
Management and treatment
Management should be multidisciplinary with the aim of stabilising the cardiac and neurological manifestations and preventing angioma growth. Depending on the volume and location of the lesions, drug treatment or surgical management may be proposed for the capillary haemangiomas. Treatment with aspirin is often recommended to prevent ischemic accidents and cerebral revascularisation, a surgical intervention often indicated for a patients with Moya-moya, may be also be proposed for PHACE.
Prognosis
The prognosis depends on the severity of the clinical signs associated with the cerebral and arterial anomalies. Neurological sequelae are frequent.

                            Last update: 
                            March 2007


                            - Expert reviewer(s): 
                            Dr Hortensia ALVAREZ  - Pr Pierre LASJAUNIAS