BACKGROUND Phelan-McDermid syndrome (PMS) is a genetic condition characterized by intellectual disability, speech and language deficits, hypotonia, autism spectrum disorder, and epilepsy. PMS is caused by 22q13.33 deletions or mutations affecting SHANK3, which codes for a critical scaffolding protein in excitatory synapses. SHANK3 variants are also known to be associated with an increased risk for regression, as well as for psychiatric disorders, including bipolar disorder and catatonia. This study aimed to further describe these phenomena in PMS and to explore any relationship between psychiatric illness and regression after early childhood. METHODS Thirty-eight people with PMS were recruited to this study through the Phelan-McDermid Syndrome Foundation based on caregiver report of distinct development of psychiatric symptoms. Caregivers completed a clinician-administered semi-structured interview focused on eliciting psychiatric symptomatology. Data from the PMS International Registry were used to confirm genetic diagnoses of participants and to provide a larger sample for comparison. RESULTS The mean age of the 38 participants was 24.7 years (range = 13 to 50; SD = 10.06). Females (31 of 38 cases; 82%) and sequence variants (15 of 38 cases; 39%) were over-represented in this sample, compared to base rates in the PMS International Registry. Onset of psychiatric symptoms occurred at a mean age of 15.4 years (range = 7 to 32), with presentations marked by prominent disturbances of mood. Enduring substantial loss of functional skills after onset of psychiatric changes was seen in 25 cases (66%). Symptomst indicative of catatonia occurred in 20 cases (53%). Triggers included infections, changes in hormonal status, and stressful life events. CONCLUSIONS This study confirms that individuals with PMS are at risk of developing severe neuropsychiatric illness in adolescence or early adulthood, including bipolar disorder, catatonia, and lasting regression of skills. These findings should increase the awareness of these phenotypes and lead to earlier diagnosis and the implementation of appropriate interventions. Our findings also highlight the importance of genetic testing in the work-up of individuals with intellectual disability and acute psychiatric illness or regression. Future research is needed to clarify the prevalence and nature of psychiatric disorders and regression among larger unbiased samples of individuals with PMS.

中文翻译：

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费兰-麦克德米德综合征患者的精神疾病和退化。


背景费兰-麦克德米德综合征（PMS）是一种遗传性疾病，其特征为智力障碍、言语和语言缺陷、肌张力低下、自闭症谱系障碍和癫痫。 PMS 是由影响 SHANK3 的 22q13.33 缺失或突变引起的，SHANK3 编码兴奋性突触中的关键支架蛋白。 SHANK3 变异还已知与退化风险增加以及精神疾病（包括双相情感障碍和紧张症）风险增加相关。本研究旨在进一步描述经前综合症中的这些现象，并探讨精神疾病与幼儿期后的回归之间的关系。方法 根据护理人员关于精神症状明显发展的报告，通过 Phelan-McDermid 综合征基金会招募了 38 名经前综合症患者参加这项研究。护理人员完成了临床医生进行的半结构化访谈，重点是引出精神病学症状。来自 PMS 国际登记处的数据用于确认参与者的基因诊断并提供更大的样本进行比较。结果 38 名参与者的平均年龄为 24.7 岁（范围 = 13 至 50；SD = 10.06）。与 PMS 国际登记处的基本比率相比，该样本中女性（38 例中的 31 例；82%）和序列变异（38 例中的 15 例；39%）所占比例过高。精神症状发作的平均年龄为 15.4 岁（范围 = 7 至 32 岁），表现为明显的情绪紊乱。 25 例 (66%) 患者出现精神变化后，功能技能严重丧失。 20 例（53%）出现紧张症症状。触发因素包括感染、荷尔蒙状态的变化和生活压力事件。 结论 这项研究证实，患有经前综合症的人在青春期或成年早期有患严重神经精神疾病的风险，包括双相情感障碍、紧张症和技能持久退化。这些发现应该提高对这些表型的认识，并导致早期诊断和实施适当的干预措施。我们的研究结果还强调了基因检测在智力障碍和急性精神疾病或退化个体检查中的重要性。未来的研究需要阐明精神疾病的患病率和性质，以及经前综合症个体的较大无偏见样本中的回归。