Clinical and Molecular Characterization of PHACES syndro

首字母缩略词PHACES用于描述后颅窝畸形、血管瘤、动脉异常、主动脉缩窄和心脏缺损、眼异常以及胸骨或腹侧缺损的相关性。我们研究了一个女性患者，这种罕见的神经皮肤疾病，表现为胸骨裂，中线脐上缝，毛细血管和海绵状血管瘤的脸，胸部和四肢。对与我们的患者表型相似的PHACES患者（即，有胸骨裂和脐上缝），显示出明显的女性偏好。15/17例报告的具有这种表型的患者是女性，而只有2例男性具有这种表型。在我们的患者和她的母亲中进行了两次X-灭活研究，使用不同的组织（颊细胞和外周白色血细胞），间隔7年。患者表现出随机X-失活，而她未受影响的母亲始终表现出中度偏斜X-失活（80%/20%）。家族史是显着的血管瘤在一个阿姨和一个表妹谁是不可用的X-灭活研究。据推测，PHACES综合征是一种X-连锁显性遗传疾病，在男性中致命。与这种表型相关的显著女性偏好的其他潜在解释包括未受影响的男性中突变基因的沉默、影响X失活的突变、受损的形态调节基因，以及最有可能的代谢干扰。

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.