Murdoch Children's Research Institute, Melbourne, Australia.
University of Melbourne, Melbourne, Australia.
Eur J Hum Genet. 2021 Apr;29(4):564-574. doi: 10.1038/s41431-020-00761-1. Epub 2020 Dec 8.
Communication difficulties are a core feature of Phelan-McDermid syndrome (PMS). However, a specific speech and language phenotype has not been delineated, preventing prognostic counselling and development of targeted therapies. We examined speech, language, social and functional communication abilities in 21 individuals with PMS (with SHANK3 involvement), using standardised assessments. Mean age was 9.7 years (SD 4.1) and 57% were female. Deletion size ranged from 41 kb to 8.3 Mb. Nine participants (45%) were non-verbal. Four (19%) had greater verbal ability, speaking in at least 4-5 word sentences, but with speech sound errors. Standard scores for receptive and expressive language were low (typically >3 SD below the mean). Language age equivalency was 13-16 months on average (range 2-53 months). There was a significant association between deletion size and the ability to use phrases. Participants with smaller deletion sizes were more likely to be able to use phrases (odds ratio: 0.36, 95% CI: 0.14-0.95, p = 0.040). Adaptive behaviour (life skills) was low in all areas (>2 SD below mean). Scores in communication were markedly lower than for daily living (p = 0.008) and socialisation (p < 0.001). A common linguistic profile was characterised by severe impairment across receptive, expressive and social language domains. Yet data indicated greater communicative intent than appeared to be capitalised by current therapies. Early implementation of augmentative (e.g. computer-assisted) modes of communication, alongside promotion of oral language, is essential to harness this intent, accelerate language development and reduce frustration. Future trials should examine the added benefit of targeted speech motor interventions in those with greater verbal capacity.
沟通困难是 Phelan-McDermid 综合征（PMS）的核心特征。然而，尚未明确特定的言语和语言表型，从而无法进行预后咨询和制定靶向治疗方案。我们使用标准化评估工具，检查了 21 名 PMS 患者（涉及 SHANK3 缺失）的言语、语言、社交和功能性沟通能力，这些患者的平均年龄为 9.7 岁（标准差 4.1），其中 57%为女性。缺失大小范围从 41kb 到 8.3Mb。9 名患者（45%）无言语能力。4 名患者（19%）言语能力较强，能说至少 4-5 个单词的句子，但存在言语发音错误。接受性和表达性语言的标准分数较低（通常低于平均值 3 个标准差以上）。语言年龄平均相当于 13-16 个月（范围为 2-53 个月）。缺失大小与使用短语的能力之间存在显著关联。缺失较小的患者更有可能使用短语（优势比：0.36，95%置信区间：0.14-0.95，p=0.040）。所有领域的适应行为（生活技能）均较低（均低于平均值 2 个标准差以上）。沟通方面的评分明显低于日常生活（p=0.008）和社交（p<0.001）。共同的语言模式特征是在接受性、表达性和社交语言领域均存在严重障碍。然而，数据表明，与目前的治疗方法相比，患者的交流意愿更强。早期实施辅助（例如计算机辅助）沟通模式，同时促进口语语言发展，对于利用这种意愿、加速语言发展和减少挫败感至关重要。未来的试验应研究在言语运动能力较强的患者中，针对特定语言障碍进行治疗的额外益处。
