Phelan-McDermid syndrome (PMS) is a rare genetic disorder compromising the 22q13 terminal region and affecting SHANK3, a gene crucial to the neurobehavioural phenotype and strongly linked to autism (ASD) and intellectual disability (ID). The condition is characterised by global developmental delay, ID, speech impairments, hypotonia and autistic behaviours, although its presentation and symptom severity vary widely. In this study, we provide a thorough description of the behavioural profile in PMS and explore differences related to deletion size and language ability. We used standard clinical assessment instruments to measure altered behaviour, adaptive skills and autistic symptomatology in sixty participants with PMS (30 females, median age 8.5 years, SD=7.1). We recorded background information and other clinical manifestations and explored associations with deletion size. We performed descriptive and inferential analyses for group comparison. We found delayed gross and fine motor development, delayed and impaired language (~70% of participants non or minimally verbal), ID of different degrees and adaptive functioning ranging from severe to borderline impairment. Approximately 40% of participants experienced developmental regression, and half of those regained skills. Autistic symptoms were frequent and variable in severity, with a median ADOS-2 CSS score of 6 for every domain. Sensory processing anomalies, hyperactivity, attentional problems and medical comorbidities were commonplace. The degree of language and motor development appeared to be associated with deletion size. This study adds to previous research on the clinical descriptions of PMS and supports results suggesting wide variability of symptom severity and its association with deletion size. It makes the case for suitable psychotherapeutic and pharmacological approaches, for longitudinal studies to strengthen our understanding of possible clinical courses and for more precise genomic analysis.

中文翻译：

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Phelan-McDermid 综合征临床表型的表征

Phelan-McDermid 综合征 (PMS) 是一种罕见的遗传疾病，影响 22q13 末端区域并影响 SHANK3，SHANK3 是一种对神经行为表型至关重要的基因，与自闭症 (ASD) 和智力障碍 (ID) 密切相关。该病症的特征是全面发育迟缓、智力障碍、语言障碍、张力减退和自闭症行为，尽管其表现和症状严重程度差异很大。在这项研究中，我们全面描述了 PMS 中的行为特征，并探讨了与删除大小和语言能力相关的差异。我们使用标准临床评估工具来测量 60 名 PMS 参与者（30 名女性，中位年龄 8.5 岁，SD = 7.1）的行为改变、适应技能和自闭症症状。我们记录了背景信息和其他临床表现，并探讨了与缺失大小的关联。我们对组比较进行了描述性和推理性分析。我们发现粗大和精细运动发育延迟、语言延迟和受损（约 70% 的参与者没有语言或最低限度的语言）、不同程度的 ID 以及从严重到临界损伤的适应性功能。大约 40% 的参与者经历了发育倒退，其中一半恢复了技能。自闭症症状频繁且严重程度不同，每个领域的 ADOS-2 CSS 得分中位数为 6。感觉处理异常、多动症、注意力问题和医学合并症是司空见惯的。语言和运动发展的程度似乎与缺失大小有关。这项研究增加了先前关于 PMS 临床描述的研究，并支持表明症状严重程度存在广泛差异及其与缺失大小相关的结果。它为合适的心理治疗和药理学方法、纵向研究提供了理由，以加强我们对可能的临床过程的理解以及更精确的基因组分析。