Hägerling René
Lymphovaskuläre Medizin und Translationale 3D-Histopathologie, Institut für Medizinische Genetik und Humangenetik, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Deutschland.
BIH Center für Regenerative Therapien, Berlin Institute of Health der Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Deutschland.
Dermatologie (Heidelb). 2023 Aug;74(8):594-604. doi: 10.1007/s00105-023-05183-w. Epub 2023 Jul 4.
Primary lymphoedema is a hereditary genetic disorder of the lymphatic system. These genetic disorders can result in malformation or dysfunction of the lymphatic system, which leads to an accumulation of fluid in the tissue and, thus to the formation of oedema. The most common form is peripheral lymphoedema of the lower limbs, but systemic manifestations such as intestinal lymphangiectasia, ascites, chylothorax or hydrops fetalis may also occur. The clinical presentation and the degree of lymphoedema varies depending on the causative gene and the specific gene alteration. Primary lymphoedema is divided into five categories: (1) disorders with somatic mosaicism and segmental growth abnormality, (2a) syndromal disorders, (2b) disorders with systemic involvement, (2c) congenital lymphoedema and (2d) disorders that occur after the first year of life (late onset lymphoedema). Targeted genetic diagnosis is based on the patient's clinical presentation and classification into one of the five categories. In general, the diagnosis usually starts with basic diagnostics, which include cytogenetic and molecular genetic testing. Subsequently, a molecular genetic diagnosis is made by performing single-gene analyses, gene panel examinations, exome sequencing or whole genome sequencing. This allows the identification of genetic variants or mutations that are considered to be causative for the presenting symptoms. Combined with human genetic counselling, the genetic diagnosis allows for conclusions about inheritance, the risk of recurrence and potential concomitant symptoms. In many cases, only this approach allows the definite form of primary lymphoedema to be described.
原发性淋巴水肿是一种淋巴系统的遗传性基因疾病。这些基因疾病可导致淋巴系统畸形或功能障碍，进而导致组织中液体积聚，从而形成水肿。最常见的形式是下肢周围性淋巴水肿，但也可能出现系统性表现，如肠淋巴管扩张、腹水、乳糜胸或胎儿水肿。淋巴水肿的临床表现和程度因致病基因和特定的基因改变而异。原发性淋巴水肿分为五类：（1）伴有体细胞镶嵌现象和节段性生长异常的疾病，（2a）综合征性疾病，（2b）伴有全身受累的疾病，（2c）先天性淋巴水肿和（2d）出生后第一年之后发生的疾病（迟发性淋巴水肿）。针对性的基因诊断基于患者的临床表现，并将其归类为五类中的一类。一般来说，诊断通常从基本诊断开始，包括细胞遗传学和分子遗传学检测。随后，通过进行单基因分析、基因 panel 检测、外显子组测序或全基因组测序进行分子遗传学诊断。这有助于识别被认为是导致当前症状的基因变异或突变。结合人类遗传咨询，基因诊断可以得出关于遗传、复发风险和潜在伴随症状的结论。在许多情况下，只有这种方法才能描述原发性淋巴水肿的确切形式。
