Department of Clinical Genetics, Genetic and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia.
Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
Mol Genet Genomic Med. 2023 Jun;11(6):e2157. doi: 10.1002/mgg3.2157. Epub 2023 Mar 1.
Pathogenic variants in AXIN2 have been associated with tooth agenesis, colon polyps, and colon cancer. Given the rare nature of this phenotype, we set out to collect additional genotypic and phenotypic information.
Data were collected via a structured questionnaire. Sequencing was performed in these patients mostly due to diagnostic purpose. A little more than half of the AXIN2 variant carriers were identified by NGS; other six were family members.
Here, we report 13 individuals with a heterozygous AXIN2 pathogenic/likely pathogenic variant who have a variable expression of oligodontia-colorectal cancer syndrome (OMIM 608615) or oligodontia-cancer predisposition syndrome (ORPHA 300576). Three individuals from one family also had cleft palate, which might represent a new clinical feature of AXIN2 phenotype, also given the fact that AXIN2 polymorphisms have been found in association with oral clefting in population studies. AXIN2 has already been added to multigene cancer panel tests; further research should be conducted to determine whether it should be added to cleft lip/palate multigene panels.
More clarity about oligodontia-colorectal cancer syndrome, about the variable expression, and associated cancer risks is needed to improve clinical management and to establish guidelines for surveillance. We collected information about the surveillance that was advised, which might support clinical management of these patients.
AXIN2 的致病变异与牙齿缺失、结肠息肉和结肠癌有关。鉴于这种表型罕见，我们着手收集更多的基因型和表型信息。
通过结构化问卷收集数据。对这些患者进行测序主要是出于诊断目的。超过一半的 AXIN2 变异携带者通过 NGS 发现；其他 6 名是家庭成员。
我们在此报告了 13 名携带 AXIN2 致病/可能致病变异的杂合子患者，他们表现出不同程度的少牙-结直肠癌综合征（OMIM 608615）或少牙-癌症易感性综合征（ORPHA 300576）。一个家族的 3 名个体还患有腭裂，这可能代表 AXIN2 表型的一个新的临床特征，鉴于人群研究中已经发现 AXIN2 多态性与口腔裂有关。AXIN2 已被添加到多基因癌症面板检测中；应进一步研究是否应将其添加到唇裂/腭裂多基因面板中。
需要更多关于少牙-结直肠癌综合征的明确信息，包括其可变表达和相关癌症风险，以改善临床管理并制定监测指南。我们收集了建议的监测信息，这可能支持这些患者的临床管理。
