Clinical and Molecular Characterization of PHACES syndro

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The acronym PHACES is used to describe the association of Posterior fossa malformations, Hemangiomas, Arterial anomalies, Coarctation of the aorta and cardiac defects, Eye abnormalities, and Sternal or ventral defects. We studied a female patient with this rare neurocutaneous disorder and manifested a sternal cleft, midline supraumbilical raphe, and capillary and cavernous hemangiomas of the face, chest, and extremities. A literature review of PHACES patients with phenotypes similar to our patient (i.e., with a sternal cleft and a supraumbilical raphe), revealed a marked female predilection. Fifteen of seventeen reported patients with this phenotype were female while only two males possessed this phenotype. X-inactivation studies in both our patient and her mother were performed twice using different tissues (buccal cells and peripheral white blood cells) and with an interval of 7 years. The patient showed random X-inactivation, whereas her unaffected mother consistently showed moderately skewed X-inactivation (80%/20%). The family history was remarkable for hemangiomas in a maternal aunt and a female cousin who were unavailable for X-inactivation studies. It has been speculated that PHACES syndrome is an X-linked dominant disorder lethal in males. Other potential explanations for the marked female predilection associated with this phenotype include the silencing of a mutant gene in unaffected males, mutations affecting X-inactivation, damaged morphoregulatory genes, and, most likely, metabolic interference.