Department of Pediatrics, Georgetown University Medical Center, Washington, DC, USA.
Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, Kansas, USA.
Clin Genet. 2024 Dec;106(6):667-678. doi: 10.1111/cge.14615. Epub 2024 Sep 17.
Congenital anomalies of the kidney and urinary tract (CAKUT) and congenital heart disease (CHD) are the most common congenital defects and constitute a major cause of morbidity in children. Anomalies of both systems may be isolated or associated with congenital anomalies of other organ systems. Various reports support the co-occurrence of CAKUT and CHD, although the prevalence can vary. Cardiovascular anomalies occur in 11.2% to 34% of patients with CAKUT, and CAKUT occur in 5.3% to 35.8% of those with CHD. The co-occurrence of genetic factors in both CAKUT and CHD would raise common etiologies including genetics, genetic-environmental interactions, or shared molecular mechanisms and pathways such as NODAL, NOTCH, BMP, WNT, and VEGF. Studies in animal models and humans have indicated a genetic etiology for CHD and CAKUT with hundreds of genes recognized and thousands of entries, found in a catalog of human genetic disorders. There are over 80 CAKUT genes and over 100 CHD genes available for clinical testing. For example, the HNFIB gene accounts for 5% to 31% of reported cases of CAKUT. In view of the association between CAKUT and CHD, a thorough cardiac examination should be performed in patients with CAKUT, and a similar evaluation for CAKUT in the presence of CHD. This will allow early diagnosis and therapeutic intervention to improve the long- term outcome of patients affected, and test for at-risk family members. We present here evidence for an association of anomalies involving the two organ systems, and discuss possible etiologies of targeted genes, their functions, biological processes and interactions on embryogenesis.
先天性肾和尿路畸形（CAKUT）和先天性心脏病（CHD）是最常见的先天性缺陷，也是儿童发病的主要原因。这两个系统的异常可能是孤立的，也可能与其他器官系统的先天性异常相关。尽管患病率可能有所不同，但各种报告都支持 CAKUT 和 CHD 的共同发生。心血管异常发生在 11.2%至 34%的 CAKUT 患者中，而 CAKUT 发生在 5.3%至 35.8%的 CHD 患者中。CAKUT 和 CHD 中遗传因素的共同发生会提出共同的病因，包括遗传、遗传-环境相互作用或共同的分子机制和途径，如 NODAL、NOTCH、BMP、WNT 和 VEGF。动物模型和人类的研究表明，CHD 和 CAKUT 具有遗传病因，已有数百个基因被识别，数千个条目被收录在人类遗传疾病目录中。有超过 80 个 CAKUT 基因和超过 100 个 CHD 基因可用于临床检测。例如，HNFIB 基因占报道的 CAKUT 病例的 5%至 31%。鉴于 CAKUT 和 CHD 之间的关联，应对 CAKUT 患者进行彻底的心脏检查，并在存在 CHD 的情况下对 CAKUT 进行类似的评估。这将有助于早期诊断和治疗干预，改善受影响患者的长期预后，并对高危家属进行检测。我们在此提出了两个器官系统异常之间存在关联的证据，并讨论了靶向基因的可能病因、它们在胚胎发生中的功能、生物学过程和相互作用。
