Ma Nan, Li Zhong-Wei, Liu Jia-Jia, Liu Xing-Guang, Zhou Xing, Wang Bo-Wen, Li Yan-Ling, Zhang Tian-Cheng, Xie Ping
Department of Cardiovascular Medicine, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China.
Department of Echocardiography Room, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China.
World J Cardiol. 2025 Jun 26;17(6):106525. doi: 10.4330/wjc.v17.i6.106525.
Noonan syndrome is a relatively common autosomal dominant genetic disorder characterized by cardiovascular defects owing to functional abnormalities in key genes such as . Mutations in are typically associated with hypertrophic cardiomyopathy (HCM). However, in this case, the patient exhibited atrial and ventricular septal defects (VSDs).
This case report describes an 11-year-old boy diagnosed with Noonan syndrome, in whom genetic testing revealed a c.770C>T (p.Ser257 Leu) mutation in . The patient presented with intermittent chest discomfort and shortness of breath, symptoms that significantly worsened after physical activity. Clinical evaluation revealed marked growth retardation and multiple physical abnormalities. Electrocardiographic and echocardiographic assessments revealed VSDs, atrial septal defects, and left ventricular outflow tract obstruction. Following multidisciplinary consultation, the patient underwent cardiac surgical intervention, which led to clinical improvement; however, they subsequently developed a third-degree atrioventricular block, necessitating the implantation of a permanent pacemaker. During follow-up, echocardiographic findings demonstrated near-complete resolution of the shunt across the atrial and ventricular septa, significant improvement in left ventricular outflow tract obstruction, and notable reduction in ventricular septal thickness. A genetic mutation at the c.770C>T (p.Ser257 Leu) locus of is typically associated with HCM and pulmonary hypertension. However, this patient's clinical phenotype manifested as HCM, atrial septal defect, and VSD, suggesting that this mutation may involve a different pathophysiological mechanism.
This case confirms the genotype-phenotype heterogeneity of Noonan syndrome and highlights the complex management requirements of mutation-associated cardiac pathologies. Early surgical intervention can ameliorate structural defects, but it must be integrated with genetic counseling and lifelong monitoring to optimize patient outcomes.
努南综合征是一种相对常见的常染色体显性遗传病，其特征是由于关键基因功能异常导致心血管缺陷。[具体基因名称]的突变通常与肥厚型心肌病（HCM）相关。然而，在本病例中，患者表现为房间隔缺损和室间隔缺损（VSD）。
本病例报告描述了一名11岁男孩被诊断为努南综合征，基因检测显示[具体基因名称]存在c.770C>T（p.Ser257Leu）突变。患者出现间歇性胸部不适和呼吸急促，这些症状在体力活动后明显加重。临床评估发现明显生长发育迟缓及多种身体异常。心电图和超声心动图评估显示存在室间隔缺损、房间隔缺损和左心室流出道梗阻。经过多学科会诊后，患者接受了心脏手术干预，临床症状得到改善；然而，随后出现了三度房室传导阻滞，需要植入永久性起搏器。随访期间，超声心动图检查结果显示房间隔和室间隔分流几乎完全消失，左心室流出道梗阻明显改善，室间隔厚度显著减小。[具体基因名称]基因c.770C>T（p.Ser257Leu）位点的基因突变通常与肥厚型心肌病和肺动脉高压相关。然而，该患者的临床表型为肥厚型心肌病、房间隔缺损和室间隔缺损，提示该突变可能涉及不同的病理生理机制。
本病例证实了努南综合征的基因型-表型异质性，并突出了与[具体基因名称]突变相关的心脏病变复杂的管理需求。早期手术干预可改善结构缺陷，但必须结合遗传咨询和终身监测以优化患者预后。
