Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Office of the Clinical Director, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Am J Med Genet A. 2023 Feb;191(2):490-497. doi: 10.1002/ajmg.a.63049. Epub 2022 Dec 13.
We report a series of four unrelated adults with Smith-Magenis syndrome (SMS) and concomitant features of Birt-Hogg-Dubé (BHD) syndrome based upon haploinsufficiency for FLCN and characteristic renal cell carcinomas and/or evidence of cutaneous fibrofolliculomas. Three of the cases constitute the first known association of histopathologically verified characteristic BHD-associated renal tumors in adults with SMS; the fourth was identified to have histologically confirmed skin fibrofolliculomas. Molecular analysis documented second-hit FLCN mutations in two of the three cases with confirmed BHD renal pathology. These cases suggest the need to expand management recommendations for SMS to include kidney cancer surveillance starting at 20 years of age, as per the screening recommendations for BHD syndrome.
我们报告了一系列 4 例无关联的成人 Smith-Magenis 综合征（SMS）患者，他们具有 Birt-Hogg-Dubé（BHD）综合征的伴随特征，这是基于 FLCN 的杂合性缺失以及特征性的肾细胞癌和/或皮肤纤维毛囊瘤的证据。其中 3 例构成了首例已知的成人 SMS 与组织病理学证实的特征性 BHD 相关肾肿瘤的关联；第 4 例被确定为具有组织学证实的皮肤纤维毛囊瘤。分子分析在 3 例具有明确 BHD 肾病理的病例中记录了第二个 FLCN 突变。这些病例表明，需要根据 BHD 综合征的筛查建议，将 SMS 的管理建议扩展到包括从 20 岁开始的肾癌监测。
