ASXL3 loss-of-function variants represent a well-established cause of Bainbridge–Ropers syndrome, a syndromic neurodevelopmental disorder with intellectual and motor disabilities. Although a recent large-scale genomics-based study has suggested an association between ASXL3 variation and cerebral palsy, there have been no detailed case descriptions. We report, here, a female individual with a de novo pathogenic c.1210C > T, p.Gln404* nonsense variant in ASXL3, identified within the frame of an ongoing research project applying trio whole-exome sequencing to the diagnosis of dystonic cerebral palsy. The patient presented with a mixture of infantile-onset limb/trunk dystonic postures and secondarily evolving distal spastic contractures, in addition to more typical features of ASXL3-related diseases such as severe feeding issues, intellectual disability, speech impairment, and facial dysmorphic abnormalities. Our case study confirms a role for ASXL3 pathogenic variants in the etiology of cerebral-palsy phenotypes and indicates that dystonic features can be part of the clinical spectrum in Bainbridge–Ropers syndrome. ASXL3 should be added to target-gene lists used for molecular evaluation of cerebral palsy.

ASXL3功能丧失变体代表了 Bainbridge-Ropers 综合征的公认原因，这是一种伴有智力和运动障碍的综合征性神经发育障碍。尽管最近一项基于基因组学的大规模研究表明ASXL3变异与脑瘫之间存在关联，但没有详细的病例描述。我们在这里报告了一名女性个体，其在 ASXL3 中具有从头致病性 c.1210C > T，p.Gln404* 无义变体，在一项正在进行的研究项目的框架内确定，该项目将三重全外显子组测序应用于肌张力障碍性脑瘫的诊断。除了严重的喂养问题、智力障碍、言语障碍和面部畸形异常等ASXL3相关疾病的更典型特征外，该患者还出现了婴儿期四肢/躯干肌张力障碍姿势和继发性远端痉挛性挛缩的混合症状。我们的案例研究证实了ASXL3致病变异在脑瘫表型病因学中的作用，并表明肌张力障碍特征可能是 Bainbridge-Ropers 综合征临床谱的一部分。ASXL3应添加到用于脑瘫分子评估的靶基因列表中。