Clinical and Molecular Characterization of PHACES syndro

首字母缩略词phases用于描述后窝畸形、血管瘤、动脉异常、主动脉缩窄和心脏缺陷、眼睛异常以及胸骨或腹侧缺陷的关联。我们研究了一位患有这种罕见神经皮肤疾病的女性患者，表现为胸骨裂，脐上中线，面部，胸部和四肢的毛细血管瘤和海绵状血管瘤。文献回顾了与我们的患者表型相似的PHACES患者（即胸骨裂和脐上缝），显示了明显的女性偏好。17例报告的患者中有15例是女性，而只有2例男性具有这种表型。我们对患者及其母亲进行了两次x -失活研究，使用不同的组织（颊细胞和外周白细胞），间隔7年。患者表现为随机x -失活，而其未受影响的母亲则一贯表现为中度偏x -失活（80%/20%）。一位母阿姨和一位无法进行x -失活研究的女表亲的血管瘤家族史是值得注意的。据推测，PHACES综合征是一种致命的男性x连锁显性疾病。对于与这种表型相关的显著雌性偏好的其他潜在解释包括：未受影响的雄性突变基因沉默、影响x失活的突变、形态调节基因受损，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.