Primary lymphedema is a long-term (chronic) condition characterized by tissue lymph retention and swelling that can affect any part of the body, although it usually develops in the arms or legs. Due to the relevant contribution of the lymphatic system to human physiology, while this review mainly focusses on the clinical and physiological aspects related to the regulation of fluid homeostasis and edema, clinicians need to know that the impact of lymphatic dysfunction with a genetic origin can be wide ranging. Lymphatic gene dysfunction can affect immune function so leading to infection; it can influence cancer development and spread; and it can determine fat transport so impacting on nutrition and obesity. Genetic studies and the development of imaging techniques for the assessment of lymphatic function have enabled the recognition of primary lymphedema as a heterogenic condition in terms of genetic causes and disease mechanisms. In this review, the known biological function of several genes crucial to the development and function of the lymphatic system are used as a basis for understanding normal lymphatic biology. The disease conditions originating from mutations in these genes are discussed together with a detailed clinical description of the phenotype and the up-to-date knowledge in terms of disease mechanisms acquired from in vitro and in vivo research models.

中文翻译：

---

淋巴系统的发育和生理功能 - 淋巴水肿遗传学研究的见解

原发性淋巴水肿是一种长期（慢性）疾病，其特征是组织淋巴潴留和肿胀，可影响身体的任何部位，但通常发生在手臂或腿部。由于淋巴系统对人体生理学的相关贡献，虽然本综述主要集中于与液体稳态和水肿调节相关的临床和生理方面，但临床医生需要知道，遗传起源的淋巴功能障碍的影响可能是范围广泛。淋巴基因功能障碍会影响免疫功能，从而导致感染；它可以影响癌症的发展和扩散；它可以决定脂肪运输，从而影响营养和肥胖。遗传学研究和用于评估淋巴功能的成像技术的发展使人们认识到原发性淋巴水肿在遗传原因和疾病机制方面是一种异质性疾病。在这篇综述中，对淋巴系统发育和功能至关重要的几个基因的已知生物学功能被用作理解正常淋巴生物学的基础。讨论了源自这些基因突变的疾病状况，并结合表型的详细临床描述以及从体外和体内研究模型获得的疾病机制方面的最新知识。