Pathogenic AXIN2 variants cause absence of permanent teeth (hypodontia), sparse hair and eye brows (ectodermal dysplasia), and gastrointestinal polyps and cancer. Inheritance is autosomal dominant with variable penetrance. Only twenty- five patients have been reported from five families. A Mayo Clinic pilot program tested 3009 newly diagnosed cancer patients for pathogenic germline variants in 83 hereditary cancer genes, including AXIN2. We found only one patient with a pathogenic AXIN2 variant. The proband was a 49 year-old female who came to Otolaryngology clinic complaining of right-sided nasal obstruction. Biopsy of identified nasal polyp revealed olfactory neuroblastoma (esthesioneuroblastoma). Surgical resection with gross, total tumor resection was followed by radiation therapy. The patient enrolled in a clinical pilot of genetic testing and a pathogenic variant in AXIN2, c.1822del (p.Leu608Phefs*81) (NM_004655.3) was found. She was seen in Medical Genetics clinic and found to have a personal history of hypodontia. Her eyebrows, hair, and nails were all normal. She underwent upper endoscopy and colonoscopy. A four mm gastric adenoma was found and removed. This is the first case reported on a patient with a pathogenic, germline AXIN2 variant and an olfactory neuroblastoma or a gastric adenoma. We propose that these could be features of the AXIN2 phenotype. The known association between gastric adenomas and familial adenomatous polyposis, the other Wnt/beta-catenin disorder, supports the hypothesis that pathogenic AXIN2 variants increase risk as well. As the odds of a chance co-occurrence of a pathogenic AXIN2 variant and an olfactory neuroblastoma are so rare, it is worth exploring potential causation. We are building a clinical registry to expand understanding of the AXIN2 phenotype and request any clinicians caring for patients with pathogenic AXIN2 variants to contact us.

中文翻译：

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病例报告扩大了生殖系AXIN2相关的表型，以包括嗅觉神经母细胞瘤和胃腺瘤。

致病性AXIN2变体导致缺少恒牙（齿龈欠缺），稀疏的头发和眼眉（外胚层发育不良）以及胃肠息肉和癌症。遗传是常染色体显性遗传，具有可变的外显率。从五个家庭中仅报告了25位患者。Mayo Clinic试点计划测试了3009名新诊断的癌症患者的83个遗传性癌症基因（包括AXIN2）中的致病种系变异。我们发现只有一名患有致病性AXIN2变异的患者。该先证者是一名49岁的女性，她到耳鼻喉科诊所抱怨右侧鼻塞。鼻息肉的活检显示嗅觉神经母细胞瘤（esthesioneuroblastoma）。手术切除并进行大，全肿瘤切除，然后进行放射治疗。该患者参加了基因测试的临床试验，并发现了AXIN2的致病变体c.1822del（p.Leu608Phefs * 81）（NM_004655.3）。她曾在Medical Genetics诊所看过，发现有个人牙髓病史。她的眉毛，头发和指甲都正常。她接受了内镜和结肠镜检查。发现并切除了四毫米胃腺瘤。这是第一例有关致病性生殖系AXIN2变异和嗅觉神经母细胞瘤或胃腺瘤的患者的报道。我们建议这些可能是AXIN2表型的特征。胃腺瘤与家族性腺瘤性息肉病（另一种Wnt /β-catenin疾病）之间的已知关联支持病原性AXIN2变体也增加风险的假说。由于致病性AXIN2变体与嗅觉神经母细胞瘤同时发生的几率很小，因此值得探讨潜在的因果关系。我们正在建立临床注册中心，以扩大对AXIN2表型的了解，并要求任何照顾有致病性AXIN2变体患者的临床医生与我们联系。