Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington.
Department of Pediatrics, Division of Genetic Medicine, University of Washington/Seattle Children's Hospital, Seattle, Washington.
Am J Med Genet A. 2019 Sep;179(9):1783-1790. doi: 10.1002/ajmg.a.61281. Epub 2019 Jul 11.
Rare individuals with 20p11.2 proximal deletions have been previously reported, with a variable phenotype that includes heterotaxy, biliary atresia, midline brain defects associated with panhypopituitarism, intellectual disability, scoliosis, and seizures. Deletions have ranged in size from 277 kb to 11.96 Mb. We describe a newborn with a de novo 2.7 Mb deletion of 20p11.22p11.21 that partially overlaps previously reported deletions and encompasses FOXA2. Her clinical findings further expand the 20p11.2 deletion phenotype to include severe midline cranial and intracranial defects such as aqueductal stenosis with hydrocephalus, mesencephalosynapsis with diencephalic-mesencephalic junction dysplasia, and pyriform aperture stenosis. We also report one individual with a missense variant in FOXA2 who had abnormal glucose homeostasis, panhypopituitarism, and endodermal organ dysfunction. Together, these findings support the critical role of FOXA2 in panhypopituitarism and midline defects.
先前已有报道称，罕见的个体存在 20p11.2 近端缺失，其表型具有变异性，包括异构、胆道闭锁、与垂体功能减退相关的中线脑缺陷、智力残疾、脊柱侧凸和癫痫。缺失的大小范围从 277kb 到 11.96Mb。我们描述了一名新生儿患有 20p11.22p11.21 的新发 2.7Mb 缺失，该缺失部分与先前报道的缺失重叠，并包含 FOXA2。她的临床发现进一步扩展了 20p11.2 缺失表型，包括严重的中线颅面和颅内缺陷，如导水管狭窄伴脑积水、中脑-间脑连接发育不良伴中脑融合、以及梨状孔狭窄。我们还报告了一名 FOXA2 错义变异的个体，其表现为葡萄糖稳态异常、垂体功能减退和内胚层器官功能障碍。综上所述，这些发现支持 FOXA2 在垂体功能减退和中线缺陷中的关键作用。
