Özdede Murat
Division of General Internal Medicine, Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Türkiye;Hacettepe University, Center for Genomics and Rare Diseases, Ankara, Türkiye.
Anatol J Cardiol. 2024 Jun 14;28(9):417-28. doi: 10.14744/AnatolJCardiol.2024.4480.
Mendelian forms of renin-angiotensin-aldosterone system (RAAS)-related hypertension, commonly referred to as monogenic hypertension, represent a rare but significant subset of hypertensive disorders characterized by genetic mutations that disrupt the normal physiological mechanisms of blood pressure regulation. This review focuses on elucidating the germline mutations affecting RAAS pathways that lead to distinct forms of heritable hypertension. By understanding the pathophysiological basis of conditions such as Gordon's syndrome, Liddle syndrome, congenital adrenal hyperplasia, and familial hyperaldosteronism types, this review aims to highlight the unique clinical features, diagnostic challenges, and therapeutic implications associated with these disorders. Recognizing specific clinical presentations and family histories indicative of monogenic hypertension is crucial for diagnosis, particularly as it often manifests as early-onset hypertension, abnormalities in potassium and blood pH, and occasionally, abnormal sexual development or related syndromes. Therefore, employing a targeted diagnostic approach through next-generation sequencing is essential to pinpoint the responsible genetic mutations, enabling accurate and individualized treatment plans. The critical importance of certain readily available specific channel blockers, such as thiazides or low-dose corticosteroids, in managing these disorders must be emphasized, as they play a key role in preventing serious complications, including cerebrovascular events. As advancements in genetic and molecular sciences continue to evolve, a deeper comprehension of the mechanisms underlying RAAS-related monogenic hypertension promises to revolutionize the management of this complex disorder, offering hope for more effective and individualized treatment options.
孟德尔形式的肾素-血管紧张素-醛固酮系统（RAAS）相关高血压，通常称为单基因高血压，是高血压疾病中罕见但重要的一个子集，其特征是基因突变破坏了血压调节的正常生理机制。本综述着重阐明影响RAAS途径的种系突变，这些突变导致了不同形式的遗传性高血压。通过了解诸如戈登综合征、利德尔综合征、先天性肾上腺增生以及家族性醛固酮增多症等疾病的病理生理基础，本综述旨在突出与这些疾病相关的独特临床特征、诊断挑战及治疗意义。认识到单基因高血压的特定临床表现和家族病史对于诊断至关重要, 尤其是因为它常表现为早发性高血压、钾和血液pH值异常，偶尔还会出现性发育异常或相关综合征。因此，采用下一代测序的靶向诊断方法对于确定相关基因突变至关重要，从而能够制定准确且个性化的治疗方案。必须强调某些易于获得的特定通道阻滞剂，如噻嗪类药物或低剂量皮质类固醇，在管理这些疾病中的关键重要性，因为它们在预防包括脑血管事件在内的严重并发症方面发挥着关键作用。随着遗传和分子科学的不断进步，对RAAS相关单基因高血压潜在机制的更深入理解有望彻底改变这种复杂疾病的管理方式，为更有效和个性化的治疗选择带来希望。
