Axenfeld‐Rieger syndrome is a genetic condition characterized by ocular and systemic features and is most commonly caused by variants in the FOXC1 or PITX2 genes. Facial dysmorphism is part of the syndrome but the differences between both genes have never been systematically assessed. Here, 11 facial traits commonly reported in Axenfeld‐Rieger syndrome were assessed by five clinical geneticists blinded to the molecular diagnosis. Individuals were drawn from the Australian and New Zealand Registry of Advanced Glaucoma in Australia or recruited through the Genetic and Ophthalmology Unit of l'Azienda Socio‐Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda in Italy. Thirty‐four individuals from 18 families were included. FOXC1 variants were present in 64.7% of individuals and PITX2 variants in 35.3% of individuals. A thin upper lip (55.9%) and a prominent forehead (41.2%) were common facial features shared between both genes. Hypertelorism/telecanthus (81.8% vs 25.0%, p = 0.002) and low‐set ears (31.8% vs 0.0%, p = 0.036) were significantly more prevalent in individuals with FOXC1 variants compared with PITX2 variants. These findings may assist clinicians in reaching correct clinical and molecular diagnoses, and providing appropriate genetic counseling.

中文翻译：

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由 FOXC1 和 PITX2 变异引起的 Axenfeld-Rieger 综合征的基因特异性面部畸形

Axenfeld-Rieger 综合征是一种以眼部和全身特征为特征的遗传病，最常见的原因是FOXC1或PITX2基因的变异。面部畸形是该综合征的一部分，但从未系统地评估这两个基因之间的差异。在这里，五位对分子诊断不知情的临床遗传学家评估了 Axenfeld-Rieger 综合征中常见的 11 种面部特​​征。个体来自澳大利亚和新西兰的晚期青光眼登记处，或通过意大利 l'Azienda Socio-Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda 的遗传和眼科部门招募。包括来自 18 个家庭的 34 个人。FOXC164.7% 的个体存在变异体，35.3% 的个体存在PITX2变异体。上唇薄（55.9%）和前额突出（41.2%）是两个基因共有的共同面部特征。与PITX2变异体相比，具有FOXC1变异体的个体中远距症/棘突（81.8% vs 25.0%，p = 0.002）和低位耳朵（31.8% vs 0.0%，p = 0.036）明显更普遍。这些发现可能有助于临床医生做出正确的临床和分子诊断，并提供适当的遗传咨询。