Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Am J Med Genet A. 2018 Dec;176(12):2575-2586. doi: 10.1002/ajmg.a.40499. Epub 2018 Oct 5.
Pallister-Killian syndrome (PKS) is a tissue limited mosaic disorder, characterized by variable degrees of neurodevelopmental delay and intellectual disability, typical craniofacial findings, skin pigmentation anomalies and multiple congenital malformations. The wide phenotypic spectrum of PKS in conjunction with the mosaic distribution of the i(12p) makes PKS an underdiagnosed disorder. Recognition of prenatal findings that should raise a suspicion of PKS is complicated by the fragmentation of data currently available in the literature and challenges in diagnosing a mosaic diagnosis on prenatal testing. Ultrasound anomalies, especially congenital diaphragmatic hernia, congenital heart defects, and rhizomelic limb shortening, have been related to PKS, but they are singularly not specific and are not present in all affected fetuses. We have combined prenatal data from 86 previously published reports and from our cohort of 114 PKS probands (retrospectively reviewed). Summarizing this data we have defined a prenatal growth profile and identified markers of perinatal outcome which collectively provide guidelines for early recognition of the distinctive prenatal profile and consideration of a diagnosis of PKS as well as for management and genetic counseling.
帕利斯特-基利安综合征(Pallister-Killian syndrome,PKS)是一种组织局限性嵌合体疾病,其特征为不同程度的神经发育迟缓及智力障碍、典型的颅面特征、皮肤色素异常和多种先天性畸形。PKS 具有广泛的表型谱,同时存在 i(12p)的嵌合分布,这使得 PKS 成为一种漏诊疾病。由于目前文献中数据的碎片化以及在产前检测中诊断嵌合体诊断的挑战,认识到应怀疑 PKS 的产前发现变得复杂。超声异常,特别是先天性膈疝、先天性心脏缺陷和肢端短缩,与 PKS 相关,但它们并不特异,并非所有受影响的胎儿都存在。我们结合了来自 86 份先前发表的报告和我们的 114 名 PKS 先证者队列(回顾性审查)的产前数据。总结这些数据,我们定义了一种产前生长模式,并确定了围产期结局的标志物,这些标志物共同为早期识别独特的产前模式、考虑 PKS 的诊断以及管理和遗传咨询提供了指导。