Department of Genetics, Cook Children's Hospital, Fort Worth, Texas, USA.
Division of Genetics and Metabolism, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Am J Med Genet A. 2023 Nov;191(11):2743-2748. doi: 10.1002/ajmg.a.63389. Epub 2023 Sep 7.
Moebius syndrome is a congenital cranial dysinnervation disorder (CCDD) that presents with nonprogressive cranial nerve (CN) VI and VII palsies resulting in facial weakness and inability to abduct the eye(s). While many CCDDs have an underlying genetic cause, the etiology of Moebius syndrome remains unclear as most cases are sporadic. Here, we describe a pair of monochorionic, diamniotic twin girls; one with normal growth and development, and one with micrognathia, reduced facial expression, and poor feeding. Magnetic resonance imaging of the brain performed on the affected twin at 19 months of age showed severely hypoplastic or absent CN IV bilaterally, left CN VI smaller than right, and bilateral hypoplastic CN VII and IX, consistent with a diagnosis of a CCDD, most similar to that of Moebius syndrome. Genomic sequencing was performed on each twin and data was assessed for discordant variants, as well as variants in novel and CCDD-associated genes. No pathogenic, likely pathogenic, or variants of uncertain significance were identified in genes known to be associated with CCDDs or other congenital facial weakness conditions. This family provides further evidence in favor of a stochastic event as the etiology in Moebius syndrome, rather than a monogenic condition.
Moebius 综合征是一种先天性颅神经支配障碍（CCDD），表现为进行性颅神经（CN）VI 和 VII 麻痹，导致面部无力和眼睛不能外展。虽然许多 CCDD 有潜在的遗传原因，但 Moebius 综合征的病因仍不清楚，因为大多数病例是散发性的。在这里，我们描述了一对单绒毛膜、双羊膜的双胞胎女孩；一个生长发育正常，另一个有小颌畸形、面部表情减少和喂养不良。受影响的双胞胎在 19 个月大时进行的大脑磁共振成像显示双侧 CN IV 严重发育不良或缺失，左侧 CN VI 小于右侧，双侧 CN VII 和 IX 发育不良，符合 CCDD 的诊断，最类似于 Moebius 综合征。对每个双胞胎进行了基因组测序，并评估了数据中的不一致变体，以及新的和与 CCDD 相关的基因中的变体。在已知与 CCDD 或其他先天性面部无力疾病相关的基因中，未发现致病性、可能致病性或意义不明的变体。这个家庭提供了更多的证据，支持 Moebius 综合征的病因是随机事件，而不是单基因疾病。
