Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Am J Med Genet A. 2021 Jun;185(6):1700-1711. doi: 10.1002/ajmg.a.62156. Epub 2021 Mar 10.
Over the past decade, pathogenic variants in all members of the ASXL family of genes, ASXL1, ASXL2, and ASXL3, have been found to lead to clinically distinct but overlapping syndromes. Bohring-Opitz syndrome (BOPS) was first described as a clinical syndrome and later found to be associated with pathogenic variants in ASXL1. This syndrome is characterized by developmental delay, microcephaly, characteristic facies, hypotonia, and feeding difficulties. Subsequently, pathogenic variants in ASXL2 were found to lead to Shashi-Pena syndrome (SHAPNS) and in ASXL3 to lead to Bainbridge-Ropers syndrome (BRPS). While SHAPNS and BRPS share many core features with BOPS, there also seem to be emerging clear differences. Here, we present five cases of BOPS, one case of SHAPNS, and four cases of BRPS. By adding our cohort to the limited number of previously published patients, we review the overlapping features of ASXL-related diseases that bind them together, while focusing on the characteristics that make each neurodevelopmental syndrome unique. This will assist in diagnosis of these overlapping conditions and allow clinicians to more comprehensively counsel affected families.
在过去的十年中，已经发现 ASXL 家族基因（ASXL1、ASXL2 和 ASXL3）的所有成员的致病性变异都会导致具有明显临床差异但又相互重叠的综合征。Bohring-Opitz 综合征（BOPS）最初被描述为一种临床综合征，后来发现与 ASXL1 的致病性变异有关。该综合征的特征是发育迟缓、小头畸形、特征性面容、低张力和喂养困难。随后，ASXL2 的致病性变异被发现会导致 Shashi-Pena 综合征（SHAPNS），ASXL3 的致病性变异会导致 Bainbridge-Ropers 综合征（BRPS）。虽然 SHAPNS 和 BRPS 与 BOPS 有许多核心特征，但似乎也有一些明显的差异正在显现。在这里，我们报告了 5 例 BOPS、1 例 SHAPNS 和 4 例 BRPS。通过将我们的队列添加到以前发表的少数患者中，我们回顾了 ASXL 相关疾病的重叠特征，将它们联系在一起，同时关注使每种神经发育综合征独特的特征。这将有助于这些重叠病症的诊断，并使临床医生能够更全面地为受影响的家庭提供咨询。
