Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is due to heterozygous FOXL2 intragenic mutations in about 70% of the patients, whereas total or partial gene deletions account for a minority of cases. Alteration of FOXL2 regulatory elements has been rarely described in patients with BPES. In this study, a prepubertal girl with BPES due to a 197-kb de novo deletion of the regulatory elements upstream of FOXL2 is reported. This girl presented with additional clinical features such as a soft cleft palate and microcephaly; thus, this copy number variant might have other somatic effects. The present deletion encompasses 2 coding genes (MRPS22 and COPB2), whose homozygous mutations have been associated with microcephaly. In our case, the sequences of the non-deleted allele were normal, ruling out a compound genetic defect. Normal levels of new biomarkers of ovarian reserve (anti-müllerian hormone, inhibin B) likely indicate an early diagnosis of type 2 BPES, but an evolutive gonadal damage will be excluded only by long-term follow-up. Additional reports of microdeletions upstream of FOXL2 are needed to better define the underlying genetic mechanism and the related phenotypic spectrum; the ability of the new hormonal markers to predict ovarian function in adolescence and adulthood should be confirmed.

中文翻译：

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支气管上睑下垂，眼睑下垂，上can逆性综合征：FOXL2上游有197kb缺失的新报道和文献复习。

大约70％的患者归因于杂合子FOXL2基因内突变，导致了支原体增生，上睑下垂和上can逆转综合征（BPES），而全部或部分基因缺失占少数病例。BPES患者很少描述FOXL2调节元件的改变。在这项研究中，据报道，由于FOXL2上游调控元件从头缺失197 KB，青春期前患有BPES的女孩。这个女孩还表现出其他临床特征，例如left裂软和小头畸形。因此，该拷贝数变体可能具有其他体细胞效应。目前的缺失包括2个编码基因（MRPS22和COPB2），它们的纯合突变与小头畸形有关。在我们的案例中，未删除的等位基因序列正常，排除了复合遗传缺陷。卵巢储备中新的生物标志物（抗苗勒管激素，抑制素B）的正常水平可能表明2型BPES的早期诊断，但长期随访不能排除对性腺的侵犯。还需要有关FOXL2上游微缺失的其他报道，以更好地确定潜在的遗传机制和相关的表型谱。应当确认新的荷尔蒙标记物预测青春期和成年期卵巢功能的能力。