Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Endocrinology, Shenzhen Children's Hospital, Shenzhen, China.
Mol Genet Genomic Med. 2023 Sep;11(9):e2192. doi: 10.1002/mgg3.2192. Epub 2023 May 10.
Rubinstein-Taybi syndrome (RSTS) is a rare autosomal-dominant genetic disease caused by variants of CREBBP (RSTS1) or EP300 (RSTS2) gene. RSTS2 is much less common, with less than 200 reported cases worldwide to date. More reports are still needed to increase the understanding of its clinical manifestations and genetic characteristics.
The clinical data of two children with RSTS2 were analyzed retrospectively, and their clinical manifestations, auxiliary examinations, and mutational spectrum were summarized. Liquid chromatography-tandem mass spectrometer (LC-MS/MS) technology was used to detect the levels of steroid hormones if possible.
After analyzing the clinical and genetic characteristics of two boys with RSTS2 (0.7 and 10.4 years old, respectively) admitted in our hospital, we identified two novel heterozygous variants in the EP300 exon 22 (c.3750C > A, p. Cys1250*, pathogenic; c.1889A > G, p. Tyr630Cys, likely pathogenic), which could account for their phenotype. In addition to common clinical manifestations such as special facial features, microcephaly, growth retardation, intellectual disability, speech delay, congenital heart defect, recurrent respiratory infections, and immunodeficiency, we found one of them had a rare feature of adrenal insufficiency, and LC-MS/MS detection showed an overall decrease in steroid hormones.
In our study, we identified two novel variants in the EP300 exon 22, and for the first time, we reported a case of RSTS2 associated with adrenal insufficiency, which will enrich the clinical and mutational spectrum of this syndrome.
Rubinstein-Taybi 综合征（RSTS）是一种罕见的常染色体显性遗传疾病，由 CREBBP（RSTS1）或 EP300（RSTS2）基因突变引起。RSTS2 较为少见，全球目前报道的病例不足 200 例。为了提高对其临床表现和遗传特征的认识，仍需更多的报道。
回顾性分析我院收治的 2 例 RSTS2 患儿的临床资料，总结其临床表现、辅助检查及基因突变谱。有条件者采用液相色谱-串联质谱（LC-MS/MS）技术检测类固醇激素水平。
对我院收治的 2 例 RSTS2 患儿（分别为 0.7 岁和 10.4 岁）的临床和遗传学特征进行分析后，我们发现 EP300 外显子 22 存在 2 个杂合变异（c.3750C > A，p. Cys1250*，致病性；c.1889A > G，p. Tyr630Cys，可能致病性），可以解释他们的表型。除了特殊面容、小头畸形、生长发育迟缓、智力障碍、语言发育迟缓、先天性心脏病、反复呼吸道感染和免疫缺陷等常见临床表现外，我们发现其中 1 例存在罕见的肾上腺皮质功能不全，LC-MS/MS 检测结果显示类固醇激素总体减少。
在本研究中，我们发现了 EP300 外显子 22 中的 2 个新变异，首次报道了 1 例与肾上腺皮质功能不全相关的 RSTS2 病例，这将丰富该综合征的临床和基因突变谱。
