Center for Rett Syndrome, Kennedy Center, Department of Paediatrics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Applied Human Molecular Genetics, Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Clin Genet. 2019 Feb;95(2):221-230. doi: 10.1111/cge.13153. Epub 2018 Jan 25.
The differential diagnostics in Rett syndrome has evolved with the development of next generation sequencing-based techniques and many patients have been diagnosed with other syndromes or variants in newly described genes where the associated phenotype(s) is yet to be fully explored. The term Rett-like refers to phenotypes with distinct overlapping features of Rett syndrome where the clinical criteria are not completely fulfilled. In this study we have combined a review of Rett-like disorders with data from a Danish cohort of 35 patients with Rett-like phenotypes emphasizing the diagnostic overlap with Pitt-Hopkins syndrome, Cornelia de Lange syndrome with SMC1A variants, and epileptic encephalopathies, for example, due to STXBP1 variants. We also found a patient with a pathogenic variant in KCNB1, which has not been previously linked to a Rett-like phenotype. This study underlines the clinical and genetic heterogeneity of a Rett syndrome spectrum, and provides an overview of the Rett syndrome-related genes described to date, and hence serves as a guide for diagnosing patients with Rett-like phenotypes.
瑞特综合征的鉴别诊断随着基于下一代测序技术的发展而不断演变，许多患者被诊断为其他综合征或新描述基因的变异，而这些综合征或变异的相关表型尚未得到充分探索。“类瑞特综合征”一词是指具有明显重叠的瑞特综合征特征的表型，但不完全符合临床标准。在这项研究中，我们结合了对类瑞特综合征障碍的回顾和来自丹麦 35 名类瑞特综合征表型患者队列的数据，强调了与皮特-霍普金斯综合征、SMC1A 变异型科恩利-戴兰格综合征和癫痫性脑病的诊断重叠，例如 STXBP1 变异。我们还发现了一名患者存在 KCNB1 的致病性变异，而 KCNB1 此前与类瑞特综合征表型无关。本研究强调了瑞特综合征谱的临床和遗传异质性，并概述了迄今为止描述的瑞特综合征相关基因，因此可为诊断类瑞特综合征患者提供指导。
