Department of Pediatrics, Amalia Children's Hospital, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands.
Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands.
Am J Med Genet A. 2022 Nov;188(11):3242-3261. doi: 10.1002/ajmg.a.62955. Epub 2022 Aug 18.
Noonan syndrome (NS) has been associated with an increased risk of lymphatic anomalies, with an estimated prevalence of 20%. The prevalence of lymphatic anomalies seems to differ between pathogenic variants. Therefore, this study aims to describe the clinical presentation, prevalence and genotype-phenotype correlations of lymphatic anomalies during life in patients with NS. This retrospective cohort study included patients (n = 115) who were clinically and genetically diagnosed with NS and visited the Noonan expertise Center of the Radboud University Medical Center between January 2015 and March 2021. Data on lymphatic anomalies during lifetime were obtained from medical records. Lymphatic anomalies most often presented as an increased nuchal translucency, chylothorax and/or lymphedema. Prenatal lymphatic anomalies increased the risk of lymphatic anomalies during infancy (OR 4.9, 95% CI 1.7-14.6). The lifetime prevalence of lymphatic anomalies was 37%. Genotype-phenotype correlations showed an especially high prevalence of lymphatic anomalies during infancy and childhood in patients with a pathogenic SOS2 variant (p = 0.03 and p < 0.01, respectively). This study shows that patients with NS have a high predisposition for developing lymphatic anomalies during life. Especially patients with prenatal lymphatic anomalies have an increased risk of lymphatic anomalies during infancy. Genotype-phenotype correlations were found in pathogenic variants in SOS2.
努南综合征（NS）与淋巴异常的风险增加有关，估计患病率为 20%。淋巴异常的患病率似乎在致病变异体之间存在差异。因此，本研究旨在描述 NS 患者一生中淋巴异常的临床表型、患病率和基因型-表型相关性。这项回顾性队列研究纳入了 2015 年 1 月至 2021 年 3 月期间在 Radboud 大学医学中心努南专业中心就诊并经临床和基因诊断为 NS 的患者（n=115）。从病历中获取了一生中淋巴异常的数据。淋巴异常最常表现为颈后透明层增加、乳糜胸和/或淋巴水肿。产前淋巴异常增加了婴儿期出现淋巴异常的风险（OR 4.9，95%CI 1.7-14.6）。淋巴异常的终生患病率为 37%。基因型-表型相关性显示，SOS2 致病性变异体患者在婴儿期和儿童期的淋巴异常患病率特别高（分别为 p=0.03 和 p<0.01）。本研究表明，NS 患者在一生中发生淋巴异常的倾向很高。特别是产前有淋巴异常的患者，婴儿期发生淋巴异常的风险增加。在 SOS2 中的致病性变异体中发现了基因型-表型相关性。
