Department of Diagnostic and Interventional Radiology, University of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
Department of Pediatric Cardiology, Children's Hospital, University of Bonn, Bonn, Germany.
Sci Rep. 2022 Jul 1;12(1):11164. doi: 10.1038/s41598-022-13806-w.
Noonan syndrome is associated with complex lymphatic abnormalities. We report dynamic-contrast enhanced MR lymphangiography (DCMRL) findings in children and adults with Noonan syndrome to further elucidate this complex disease spectrum. A retrospective evaluation of patients with confirmed Noonan syndrome and clinical signs of lymphatic dysfunction undergoing DCMRL between 01/2019 and 04/2021 was performed. MRL included T2-weighted imaging (T2w) and DCMRL. Clinical history/presentation and genetic variants were recorded. T2w-imaging was evaluated for central lymphatic abnormalities and edema distribution. DCMRL was evaluated regarding the presence of cisterna chyli/thoracic duct, lymphatic leakages, pathological lymphatic reflux and abnormal lymphatic perfusion. The time from start of contrast-injection to initial enhancement of the thoracic duct venous junction was measured to calculate the speed of contrast propagation. Eleven patients with Noonan syndrome with lymphatic abnormalities (5 female, 6 male; 7 infants, 4 adults; mean age 10.8 ± 16.4 years) were identified (PTPN11 n = 5/11 [45.5%], RIT1 n = 5/11 [45.5%], KRAS n = 1/11 [9%]). Patients had a chylothorax (n = 10/11 [91%]) and/or pulmonary lymphangiectasia [dilated pulmonary lymph vessels] (n = 9/11 [82%]). Mediastinal/pulmonary edema was depicted in 9/11 (82%) patients. The thoracic duct (TD) was (partially) absent in 10/11 (91%) cases. DCMRL showed lymphatic reflux into intercostal (n = 11/11 [100%]), mediastinal (n = 9/11 [82%]), peribronchial (n = 8/11 [73%]), peripheral (n = 5/11 [45.5%]) and genital lymphatics (n = 4/11 [36%]). Abnormal pulmonary/pleural lymphatic perfusion was seen in 8/11 patients (73%). At infancy peripheral/genital edema was more prevalent in patients with RIT1 than PTPN11 (n = 3/5 vs. n = 0/5). Compared to patients with PTPN11 who had fast lymphatic enhancement in 4/5 patients, enhancement took markedly longer in 4/5 patients with RIT1-mutations. Thoracic duct dysplasia, intercostal reflux and pulmonary/pleural lymphatic perfusion are characteristic findings in patients with Noonan syndrome presenting with chylothorax and/or pulmonary lymphangiectasia. Central lymphatic flow abnormalities show possible phenotypical differences between PTPN11 and RIT1-mutations.
努南综合征与复杂的淋巴异常有关。我们报告了儿童和成人努南综合征患者的动态对比增强磁共振淋巴管造影（DCMRL）结果，以进一步阐明这种复杂的疾病谱。对 2019 年 1 月至 2021 年 4 月期间接受 DCMRL 检查并伴有淋巴功能障碍临床症状的确诊努南综合征患者进行了回顾性评估。MRL 包括 T2 加权成像（T2w）和 DCMRL。记录了临床病史/表现和遗传变异。T2w 成像用于评估中央淋巴管异常和水肿分布。DCMRL 用于评估腔静脉/胸导管、淋巴渗漏、病理性淋巴反流和异常淋巴灌注的存在。测量从对比剂注射开始到胸导管静脉交界处初始增强的时间，以计算对比剂传播速度。确定了 11 例伴有淋巴异常的努南综合征患者（5 名女性，6 名男性；7 例婴儿，4 例成人；平均年龄 10.8±16.4 岁）（PTPN11 n=5/11 [45.5%]，RIT1 n=5/11 [45.5%]，KRAS n=1/11 [9%]）。患者有乳糜胸（n=10/11 [91%]）和/或肺淋巴管扩张症（扩张的肺淋巴管）（n=9/11 [82%]）。9/11（82%）例患者显示纵隔/肺部水肿。10/11（91%）例患者的胸导管（TD）缺失。DCMRL 显示淋巴反流到肋间（n=11/11 [100%]）、纵隔（n=9/11 [82%]）、支气管周围（n=8/11 [73%]）、外周（n=5/11 [45.5%]）和生殖器（n=4/11 [36%]）淋巴管。8/11（73%）例患者出现异常的肺/胸膜淋巴灌注。在婴儿期，RIT1 患者比 PTPN11 患者更易出现外周/生殖器水肿（n=3/5 比 n=0/5）。与 PTPN11 患者相比，4/5 例 RIT1 突变患者的淋巴增强明显更长。胸导管发育不良、肋间反流和肺/胸膜淋巴灌注是伴有乳糜胸和/或肺淋巴管扩张症的努南综合征患者的特征性表现。中央淋巴管血流异常显示 PTPN11 和 RIT1 突变之间可能存在表型差异。
