Pathogenic variants in DDX3X are associated with neurodevelopmental disorders. Communication impairments are commonly reported, yet specific speech and language diagnoses have not been delineated, preventing prognostic counseling and targeted therapies. Here, we characterized speech and language in 38 female individuals, aged 1.69–24.34 years, with pathogenic and likely pathogenic DDX3X variants (missense, n = 13; nonsense, n = 12; frameshift, n = 7; splice site, n = 3; synonymous, n = 2; deletion, n = 1). Standardized speech, language, motor, social, and adaptive behavior assessments were administered. All participants had gross motor deficits in infancy (34/34), and fine motor deficits were common throughout childhood (94%; 32/34). Intellectual disability was reported in 86% (24/28) of participants over 4 years of age. Expressive, receptive, and social communication skills were, on average, severely impaired. However, receptive language was significantly stronger than expressive language ability. Over half of the assessed participants were minimally verbal (66%; 22/33; range = 2 years 2 months–24 years 4 months; mean = 8 years; SD = 6 years) and augmented speech with sign language, gestures, or digital devices. A quarter of the cohort had childhood apraxia of speech (25%; 9/36). Despite speech and language impairments, social motivation was a relevant strength. Many participants used augmentative and alternative communication (AAC), underscoring the need for early, tailored, and comprehensive AAC intervention.

中文翻译：

---

DDX3X 神经发育障碍中的言语和语言：呼吁早期增强性和替代性沟通干预

致病变异DDX3X与神经发育障碍有关。沟通障碍很常见，但尚未描述具体的言语和语言诊断，从而妨碍了预后咨询和靶向治疗。在这里，我们对 38 名年龄在 1.69-24.34 岁的女性个体的言语和语言进行了表征，这些女性具有致病性和可能致病性DDX3X变体（错义，n= 13；废话，n= 12；移码,n= 7; 剪接位点,n= 3；同义，n= 2；删除，n= 1). 进行了标准化的言语、语言、运动、社交和适应性行为评估。所有参与者在婴儿期都有粗大运动缺陷（34/34），精细运动缺陷在整个童年时期都很常见（94%；32/34）。86% (24/28) 的 4 岁以上参与者报告有智力障碍。平均而言，表达能力、接受能力和社交沟通能力都严重受损。然而，接受性语言能力明显强于表达性语言能力。超过一半的接受评估的参与者很少使用言语（66%；22/33；范围 = 2 年 2 个月 - 24 年 4 个月；平均值 = 8 年；标清= 6 年）以及通过手语、手势或数字设备增强语音。四分之一的人患有儿童期言语失用症（25%；9/36）。尽管存在言语和语言障碍，但社交动机是一种相关的优势。许多参与者使用了增强性和替代性沟通 (AAC)，强调了早期、量身定制和全面的 AAC 干预的必要性。