An updated classification of primary lymphedema of extremity based on age of onset, lymphatic anomalies and genetics
10.3760/cma.j.cn114453-20240715-00184
- VernacularTitle:基于发病年龄、淋巴管病变和致病基因的肢体原发性淋巴水肿新分类
- Author:
Ningfei LIU
1
;
Minzhe GAO
1
Author Information
1. 上海交通大学医学院附属第九人民医院整复外科，上海 200011
- Publication Type:Journal Article
- Keywords:
Lymphedema;
Primary lymphedema;
Lymphatic dysfunction;
Lymphatic hyperplasia;
Initial lymphatic aplasia or dysfunction;
Lymphatic imaging
- From:
Chinese Journal of Plastic Surgery
2025;41(2):158-167
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To update the classification of extremity primary lymphedema (PLE) based on age of onset, lymphatic anomalies and genetics.Methods:A prospective research method was adopted. Patients with lower and upper limb PLE who visited Department of Plastic & Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine from January 207 to December 2021 were selected. Sex, age of onset, location, family history and morbidity were documented. The lymphatic imaging findings of magnetic resonance lymphography (MRL), indocyanine green lymphography (ICGL) and lymphoscintigraphy (LSG), skin tissue histology and whole exome sequencing were evaluated. Descriptive statistical method was used for data statistics.Results:A total of 1 046 patients were included, among whom 1 013 had lower extremity involvement and 33 had upper extremity involvement. Divided by the age of onset, there were 237 cases of congenital (<1 year old) and 809 of late-onset (≥1 year old), with a ratio of about 1∶4. Among the late-onset patients, most patients began to suffer the disease during adolescence (11-20 years old), with a total of 276 cases. Among patients with congenital lower limb PLE, 12.7% (26/204) had a family history. Among those with late-onset of PLE, 6.6% (53/809) had a family history. A total of 225 patients underwent whole exome sequencing (208 cases in the lower limbs and 17 cases in the upper limbs), showing that 37 patients (17.8%, 37/208) with lower limb PLE were found to carry 38 pathogenic variants in FLT4, GJC2, CELSR1, PTPN14, FOXC2 and GATA2, only 1 patient (5.9%, 1/17) with upper limb PLE was found to carry a PIEZO1 compound heterozygote variant. Three major lymphatic anomalies were identified, in which segmental lymphatic dysfunction, characterized by delayed or partial demonstration of lymph vessels, was the most common type and associated with FLT4, GJC2, CELSR1, and PTPN14 mutations. The second most common type was lymphatic hyperplasia, which was associated with FOXC2 and GATA2 variants, followed by initial lymphatic aplasia or dysfunction and associated with FLT4 and PIEZO1 mutation.Conclusion:A classification of extremity PLE is proposed based on age of onset, lymphatic anomalies and genetics, which are segmental lymphatic dysfunction, lymphatic hyperplasia, and initial lymphatic aplasia or dysfunction.
