Kobayashi Yusuke, Takeda Takashi, Kunitomi Haruko, Ueki Arisa, Misu Kumiko, Kowashi Ayari, Takahashi Takayuki, Anko Mayuka, Watanabe Keiko, Masuda Kenta, Uchida Takahito, Tominaga Eiichiro, Banno Kouji, Kosaki Kenjiro, Aoki Daisuke
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan; Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
Eur J Med Genet. 2020 Aug;63(8):103959. doi: 10.1016/j.ejmg.2020.103959. Epub 2020 May 24.
Patients with Cowden syndrome exhibit mucocutaneous lesions, hamartomatous polyposis of the gastrointestinal tract, and macrocephaly, often complicated by malignant tumors, such as breast, thyroid, and uterine cancers. Autism spectrum and epilepsy have been known as neuropsychiatric symptoms associated with Cowden syndrome; however, to the best of our knowledge, there is no report on cases complicated by schizophrenia. Here, we report a first case of Cowden syndrome complicated by schizophrenia. A 49-year-old Japanese woman started experiencing auditory hallucinations in her teens. She had left breast cancer at the age of 34 years, and right breast cancer at the age of 37 years, all of which were surgically treated. She was also being treated by oral medications for Hashimoto's disease. On consulting her previous doctor for abnormal uterine bleeding that lasted for a year, she was diagnosed with endometrial cancer. However, immediately before surgery, her auditory hallucinations and paranoid delusions became severe, and she was referred to our hospital for detailed examination and treatment. No abnormalities were found on head MRI, and she was diagnosed with schizophrenia on the basis of neuropsychiatric examination findings. After her psychiatric symptoms were controlled by 2 mg of risperidone, she underwent surgery for endometrial cancer. Although there was no apparent family history, physical findings including macrocephaly and papillomatous skin lesions together with her past medical history of multiple malignant tumors suggested Cowden syndrome. Postoperatively, genetic testing revealed a pathogenic variant c.655C > T; p. Gln219* (NM_000314.4) in PTEN, leading to the confirmation of the diagnosis of Cowden syndrome.
考登综合征患者表现出皮肤黏膜病变、胃肠道错构瘤性息肉病和巨头症，常并发恶性肿瘤，如乳腺癌、甲状腺癌和子宫癌。自闭症谱系障碍和癫痫是已知与考登综合征相关的神经精神症状；然而，据我们所知，尚无并发精神分裂症病例的报道。在此，我们报告首例考登综合征并发精神分裂症的病例。一名49岁的日本女性在十几岁时开始出现幻听。她34岁时患左乳腺癌，37岁时患右乳腺癌，均接受了手术治疗。她还因桥本氏病接受口服药物治疗。因持续一年的异常子宫出血咨询之前的医生时，她被诊断为子宫内膜癌。然而，就在手术前，她的幻听和偏执妄想变得严重，遂被转诊至我院进行详细检查和治疗。头部MRI未发现异常，根据神经精神检查结果她被诊断为精神分裂症。在2毫克利培酮控制其精神症状后，她接受了子宫内膜癌手术。尽管没有明显的家族史，但包括巨头症和乳头状皮肤病变在内的体格检查结果以及她过去患多种恶性肿瘤的病史提示考登综合征。术后，基因检测显示PTEN基因存在致病性变异c.655C>T；p.Gln219*（NM_000314.4），从而确诊为考登综合征。
