Evaluation of maternal history of miscarriage, infertility and in vitro fertilization as associated factors in PHACE.
Evaluation of maternal history of miscarriage, infertility and in vitro fertilization as associated factors in PHACE.
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评估母亲流产、不孕和体外受精史作为 PHACE 的相关因素。
DOI：
10.1111/bjd.15341
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Siegel,DH
中科院分区：
文献类型：
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作者：
Kim,ME;Cancel,M;Metry,D;Strawn,EY;Drolet,BA;Chiu,YE;Siegel,DH
亲爱的编辑，PHACE（后颅窝畸形、血管瘤、动脉畸形、主动脉缩窄和眼畸形）的病因尚不清楚。遗传病因学已被提出，但没有发表的报告遗传性的家庭儿童PHACE。PHACE有女性优势，虽然初步的X-失活研究没有表现出显着的倾斜，在受影响的女性患者或他们的母亲。1拷贝数变异研究尚未确定一种常见的致病性变异。2我们试图确定PHACE患儿的母亲流产、不孕和/或使用体外受精（IVF）的患病率是否增加。几项研究表明，接受IVF的患者中印迹障碍的发生率增加。当父亲或母亲的正常等位基因被表观遗传学沉默（印记），而来自另一个父母的突变等位基因被表达时，就会发生印记疾病。以前的研究表明，IVF可能不是印记疾病的唯一原因，而是生育能力低下的父母的遗传背景起着重要作用。3有人提出，试管婴儿可能绕过自然选择机制，允许发生印迹障碍。4 PHACE综合征国际临床登记处成立于2006年，在本研究时有218个家庭入选。在登记时，只有174个家庭提供了关于母亲流产和不育史的信息。为了进一步调查登记研究中母亲流产、不孕和IVF史的发生率，使用SurveyMonkey Platinum（https：//www.我是猴子。co.uk），并发送给登记册中有电子邮件联系信息的参与人（114个家庭）。从2014年12月14日至2015年2月4日收集了54份答复。当将调查结果与美国流产、不孕和IVF使用率进行比较时，使用v2检验计算P值。在登记数据库中的174个家庭中有59个（3349%）报告了已知或疑似流产史，而54个调查受访者中有22个（41%）。这种差异可能代表了确定偏倚。这两个比率在统计学上显著高于美国估计的流产率10-20%，P< 04001（图1a）。5在22名调查答卷人中，8人报告有两次或两次以上流产史，15%的调查答卷人报告有不育史（54人中有8人）。这一比率与美国的不孕率12%没有统计学差异，P= 0.467（图1b）。6 13%（54人中有7人）的调查答复者报告说，因与PHACE患儿有关的妊娠接受了生育治疗。这与美国1149%接受不孕不育服务的妇女相当，P= 0497（图1c）。7与美国数据相比，PHACE患儿的母亲流产率更高。流产定义为妊娠20周前已知妊娠的自然流产，复发性流产定义为两次或两次以上连续妊娠失败。5病因包括流产组织中的细胞遗传学异常（50%为自发性流产，35%为复发性流产）、子宫解剖异常（20%）、自身免疫和同种免疫原因（即抗磷脂抗体
DEAR EDITOR, The aetiology of PHACE (posterior fossa anomalies, haemangioma, arterial anomalies, coarctation of the aorta and eye anomalies) is unknown. A genetic aetiology has been proposed but there are no published reports of heritability in families of children with PHACE. PHACE has a female predominance, although preliminary X-inactivation studies have not demonstrated significant skewing in affected female patients or their mothers. 1 Copy-number variation studies have yet to identify a common pathogenic variant. 2 We sought to determine whether there is an increased prevalence of miscarriage, infertility and/or use of in vitro fertilization (IVF) in the mothers of children with PHACE. Several studies have suggested that the incidence of imprinting disorders is increased in patients undergoing IVF. Imprinting disorders occur when either the paternal or maternal normal allele is epigenetically silenced (imprinted) and a mutated allele from the other parent is expressed. Previous studies indicate that IVF may not be the sole cause of imprinting disorders, but rather that the genetic background of subfertile parents plays an important role. 3 It has been proposed that IVF may bypass a natural selection mechanism to allow for an imprinting disorder to occur. 4 The PHACE Syndrome International Clinical Registry was established in 2006 and had 218 families enrolled at the time of this study. Information regarding maternal history of miscarriage and infertility was available for only 174 families at the time of enrolment. To investigate further the rates of maternal history of miscarriage, infertility and IVF in the registry, an electronic survey was designed using SurveyMonkey Platinum (https://www. surve ymonkey. co. uk) and sent to registry participants for whom e-mail contact information was available (114 families). Fifty-four responses were gathered from 14 December 2014 to 4 February 2015. The v2-test was used to calculate P-values when comparing survey results with rates in the USA for miscarriage, infertility and IVF use. Known or suspected history of miscarriage was reported in 59 of 174 families in the registry database (3349%) compared with 22 of 54 survey respondents (41%). This difference likely represents an ascertainment bias. Both rates were statistically significantly higher than the estimated miscarriage rate of 10–20% in the USA, P< 04001 (Fig. 1a). 5 Of the 22 survey respondents, eight reported a history of two or more pregnancy losses.Fifteen per cent of survey respondents reported a history of infertility (eight of 54). This rate was not statistically different from the US infertility rate of 12%, P= 0467 (Fig. 1b). 6 Thirteen per cent (seven of 54) of survey respondents reported receiving fertility therapy for the pregnancy related to the child with PHACE. This is comparable with the 1149% of women in the USA receiving infertility services, P= 0497 (Fig. 1c). 7 More mothers of children with PHACE had miscarriages when compared with US data. Miscarriage is defined as the spontaneous loss of a known pregnancy before 20 weeks of gestation, and recurrent pregnancy loss has been defined as two or more failed consecutive pregnancies. 5 Aetiologies include cytogenetic abnormalities in the miscarriage tissue (50% for spontaneous pregnancy loss and 35% for recurrent pregnancy loss), anatomical uterine anomalies (20%), autoimmune and alloimmune causes (ie antiphospholipid antibody