Heterozygous microdeletions of chromosome 2p21 encompassing only the SIX2 gene have been described in two families to date. The clinical phenotype comprised autosomal-dominant inherited frontonasal dysplasia with ptosis in one family. In the second family, conductive hearing loss was the major clinical feature described; however, the affected persons also had ptosis. Here, we present a large family combining all three predescribed features of SIX2 gene deletion. The phenotype in four affected family members in three generations consisted of bilateral congenital ptosis, epicanthus inversus, frontonasal dysplasia with broad nasal bridge and hypertelorism, frontal bossing and large anterior fontanel in childhood, narrow ear canals, and mild conductive hearing loss with onset in childhood. Thus, the phenotypic spectrum of SIX2 haploinsufficiency is widened. Moreover, 2p21 microdeletions with SIX2 haploinsufficiency appear to lead to a recognizable phenotype with facial features resembling blepharophimosis-ptosis-epicanthus inversus syndrome.

中文翻译：

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SIX2基因单倍体不足会导致可识别的表型，包括上睑下垂，额鼻发育异常和传导性听力丧失。

迄今为止，已经在两个家族中描述了仅包含SIX2基因的2p21号染色体的杂合微缺失。在一个家庭中，临床表型包括常染色体显性遗传的前额叶发育异常伴上睑下垂。在第二个家族中，传导性听力损失是所描述的主要临床特征。但是，受影响的人也有上睑下垂。在这里，我们提出了一个结合了SIX2基因缺失的所有三个前述特征的大家族。在三代中有四个受影响的家庭成员的表型包括双侧先天性上睑下垂，上epi倒vers，额鼻发育异常，宽鼻梁桥和肥大，儿童的额突和前额large大，童年的耳道狭窄和童年发作的轻度传导性听力损失。因此，SIX2单倍型不足的表型谱变宽。此外，具有SIX2单倍体功能不足的2p21微缺失似乎导致可识别的表型，其面部特征类似于睑板增生-上睑下垂-逆戟鲸综合症。