Healthcare Genetics Program, School of Nursing, College of Behavioral, Social and Health Sciences, Clemson University, Clemson, SC 29634, USA.
Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Genes (Basel). 2022 Mar 17;13(3):528. doi: 10.3390/genes13030528.
Phelan-McDermid syndrome (PMS) is a multi-systemic disorder characterized by both genetic and phenotypic variability. Genetic abnormalities causing PMS span from pathogenic variants of the gene to chromosomal rearrangements affecting the 22q13 region and leading to the loss of up to over nine megabases. The clinical presentation of individuals with PMS includes intellectual disability, neonatal hypotonia, delayed or absent speech, developmental delay, and minor dysmorphic facial features. Several other features may present with differences in age of onset and/or severity: seizures, autism, regression, sleep disorders, gastrointestinal problems, renal disorders, dysplastic toenails, and disrupted thermoregulation. Among the causes of this phenotypic variability, the size of the 22q13 deletion has effects that may be influenced by environmental factors interacting with haploinsufficiency or hemizygous variants of certain genes. Another mechanism linking environmental factors and phenotypic variability in PMS involves the loss of one copy of genes like or , located at 22q13 and involved in the regulation of genomic methylation or pharmacokinetics, which are also influenced by external agents, such as diet and drugs. Overall, several non-mutually exclusive genetic and epigenetic mechanisms interact with environmental factors and may contribute to the clinical variability observed in individuals with PMS. Characterization of such factors will help to better manage this disorder.
佩兰-麦克德米德综合征（PMS）是一种多系统疾病，具有遗传和表型变异性。导致 PMS 的遗传异常范围从基因的致病性变异到影响 22q13 区域的染色体重排，导致多达 900 多个碱基对的缺失。PMS 患者的临床表现包括智力残疾、新生儿低张力、言语延迟或缺失、发育迟缓以及轻微的面部畸形特征。其他一些特征可能表现出发病年龄和/或严重程度的差异：癫痫、自闭症、退化、睡眠障碍、胃肠道问题、肾脏疾病、畸形趾甲和体温调节障碍。在这种表型变异性的原因中，22q13 缺失的大小可能受到与单倍不足或某些基因的半合子变异相互作用的环境因素的影响。另一个将环境因素与 PMS 中的表型变异性联系起来的机制涉及位于 22q13 并参与基因组甲基化或药代动力学调节的基因如 或 的一个拷贝的丢失，这些基因也受到外部因素的影响，如饮食和药物。总的来说，几种非相互排斥的遗传和表观遗传机制与环境因素相互作用，可能导致 PMS 患者观察到的临床变异性。对这些因素的特征进行描述将有助于更好地管理这种疾病。
