Department of Pediatrics B, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, 5265601, Ramat Gan, Israel.
The Institute for Rare Diseases, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel.
Pediatr Nephrol. 2022 Jul;37(7):1623-1646. doi: 10.1007/s00467-021-05374-4. Epub 2022 Jan 7.
Genetic kidney diseases contribute a significant portion of kidney diseases in children and young adults. Nephrogenetics is a rapidly evolving subspecialty; however, in the clinical setting, increased use of genetic testing poses implementation challenges. Consequently, we established a national nephrogenetics clinic to apply a multidisciplinary model.
Patients were referred from different pediatric or adult nephrology units across the country if their primary nephrologist suspected an undiagnosed genetic kidney disease. We determined the diagnostic rate and observed the effect of diagnosis on medical care. We also discuss the requirements of a nephrogenetics clinic in terms of logistics, recommended indications for referral, and building a multidisciplinary team.
Over 24 months, genetic evaluation was completed for a total of 74 unrelated probands, with an age range of 10 days to 72 years. The most common phenotypes included congenital anomalies of the kidneys and urinary tract, nephrotic syndrome or unexplained proteinuria, nephrocalcinosis/nephrolithiasis, tubulopathies, and unexplained kidney failure. Over 80% of patients were referred due to clinical suspicion of an undetermined underlying genetic diagnosis. A molecular diagnosis was reached in 42/74 probands, yielding a diagnostic rate of 57%. Of these, over 71% of diagnoses were made via next generation sequencing (gene panel or exome sequencing).
We identified a substantial fraction of genetic kidney etiologies among previously undiagnosed individuals which influenced subsequent clinical management. Our results support that nephrogenetics, a rapidly evolving field, may benefit from well-defined multidisciplinary co-management administered by a designated team of nephrologist, geneticist, and bioinformatician. A higher resolution version of the Graphical abstract is available as Supplementary information.
遗传性肾脏疾病在儿童和青年人群中占很大一部分。肾遗传学是一个快速发展的亚专科；然而，在临床环境中，基因检测的广泛应用带来了实施方面的挑战。因此，我们建立了一个国家肾遗传学诊所，应用多学科模式。
如果他们的主要肾病学家怀疑存在未确诊的遗传性肾脏疾病，来自全国各地不同的儿科或成人肾病单位的患者将被转介到我们的诊所。我们确定了诊断率，并观察了诊断对医疗的影响。我们还讨论了肾遗传学诊所在物流方面的要求、推荐的转诊指征以及建立多学科团队的问题。
在 24 个月的时间里，我们共对 74 名无血缘关系的先证者进行了基因评估，年龄范围为 10 天至 72 岁。最常见的表型包括肾脏和泌尿道先天畸形、肾病综合征或不明原因的蛋白尿、肾钙质沉着症/肾结石、肾小管病和不明原因的肾衰竭。超过 80%的患者因临床怀疑存在未确定的潜在遗传诊断而被转介。在 74 名先证者中，有 42 名确定了分子诊断，诊断率为 57%。其中，超过 71%的诊断是通过下一代测序（基因panel 或外显子组测序）完成的。
我们在以前未被诊断的个体中发现了相当一部分遗传性肾脏病因，这影响了随后的临床管理。我们的结果支持这样一种观点，即快速发展的肾遗传学领域可能受益于由指定的肾病学家、遗传学家和生物信息学家组成的多学科联合管理。一个更高分辨率的图表摘要版本可以在补充信息中找到。
