Phelan-McDermid Syndrome (PMS) is a genetic disorder, caused by haploinsufficiency of the SHANK3 gene on chromosome 22q13.3. It is characterized by neurobehavioral symptoms and signs including intellectual disability, speech and language impairment, autistic spectrum disorder (ASD), hypotonia and other motor abnormalities. In the brain, SHANK3 is expressed in neurons, especially in the synapse, and encodes a master scaffolding protein that forms a key framework in the postsynaptic density of glutamatergic synapses. Mutations in SHANK3 have also been identified in individuals with ASD, intellectual deficiency (ID) and schizophrenia. Mice deficient of Shank3 have defects in basal glutamatergic synaptic transmission in the hippocampus, and in synaptic transmission plasticity, including deficits in long term potentiation (LTP), and show behavioral deficits compatible with the clinical manifestations of PMS.

The PMS phenotype varies between affected individuals, but ID and speech and language impairment are present in all cases. ASD is present in a great majority of these individuals. Neurological examination demonstrates hypotonia and abnormalities of motor coordination, visual motor coordination and gait, in the majority of affected individuals. Sleep disturbances and increased pain tolerance are frequent parental complaints. Seizures and epilepsy are common, affecting more than 40% of individuals. Brain magnetic resonance imaging (MRI) abnormalities include corpus callosum hypoplasia, delayed myelination and white matter abnormalities, dilated ventricles, and arachnoid cysts. Recent advanced imaging anatomic studies including diffusion tensor imaging, point to abnormal brain connectivity.

The natural history of the syndrome is not yet fully known, but some individuals with PMS have a later onset of psychiatric illnesses including bipolar disease, accompanied by functional and neurological regression.

Individuals with the syndrome are treated symptomatically. Advances in understanding the pathophysiology of this syndrome and the generation of animal models have raised opportunities for a biological cure for PMS. A pilot clinical trial with Insulin Growth Factor -1 (IGF-1) showed positive effects on some behavioral core symptoms.

Phelan-McDermid 综合征 (PMS) 是一种遗传性疾病，由染色体 22q13.3 上的 SHANK3 基因单倍体不足引起。它的特点是神经行为症状和体征，包括智力障碍、言语和语言障碍、自闭症谱系障碍 (ASD)、肌张力减退和其他运动异常。在大脑中，SHANK3 在神经元中表达，特别是在突触中，并编码一种主要的支架蛋白，该蛋白在谷氨酸能突触的突触后密度中形成一个关键框架。在患有 ASD、智力缺陷 (ID) 和精神分裂症的个体中也发现了 SHANK3 的突变。缺乏 Shank3 的小鼠在海马中的基础谷氨酸能突触传递和突触传递可塑性方面存在缺陷，包括长期增强 (LTP) 缺陷，

PMS 表型在受影响的个体之间有所不同，但在所有情况下都存在 ID 和言语和语言障碍。这些人中的绝大多数都存在 ASD。在大多数受影响的个体中，神经系统检查显示肌张力减退和运动协调、视觉运动协调和步态异常。睡眠障碍和疼痛耐受性增加是父母经常抱怨的问题。癫痫发作和癫痫很常见，影响超过 40% 的人。脑磁共振成像 (MRI) 异常包括胼胝体发育不全、髓鞘形成延迟和白质异常、脑室扩张和蛛网膜囊肿。最近的先进成像解剖研究，包括扩散张量成像，指出大脑连接异常。

该综合征的自然史尚不完全清楚，但一些 PMS 患者较晚出现精神疾病，包括双相情感障碍，并伴有功能和神经功能退化。

患有该综合征的个体接受对症治疗。在了解这种综合征的病理生理学和动物模型的产生方面取得的进展为 PMS 的生物治疗提供了机会。胰岛素生长因子 -1 (IGF-1) 的初步临床试验显示对一些行为核心症状有积极影响。