Abstract
The lymphatic system, a complex physiological network of lymphatic organs and vessels, is essential for maintaining fluid homeostasis. Dysfunction of lymphatic system can lead to lymphedema, a pathology characterized by the accumulation of interstitial fluid in peripheral tissues. This study aimed to identify novel genetic variants in genes within the RAS/ MAPK pathway and assess their potential association with lymphedema onset. We conducted a retrospective analysis of the genetic and clinical data from 408 patients diagnosed with primary lymphedema. These patients were previously tested using a next-generation sequencing panel that included 28 diagnostic genes and 71 candidate genes. The analysis revealed five genetic variants in the genes LZTR1, RAF1 and MAP2K1. Among the identified variants, four of them have never been reported in the literature. In silico analysis and molecular modelling supported the possible pathogenicity of one missense variant in RAF1 (c.1344T>G; p.Ile448Met), which could affect protein activation by phosphorylation. The results of this study highlight the genes involved in the RAS/MAPK signaling pathway as potential diagnostic targets for primary lymphedema.Keywords: LZTR1, MAP2K1, primary lymphedema, RAF1, RAS/MAPK pathway
https://doi.org/10.2458/lymph.9754
Abstract
Background: To define the profile of patients presenting with chronic edema (CE) in three centers in Italy (Lymphoedema IMpact and PRevalence INTernational).
Methods and Results: Data were collected in patients referred for CE between September 2016 and July 2017. A total of 1637 were recruited, 86.7% (1419) outpatients and 13.3% (218) inpatients with 80.6% (1319) female and mean age 54 years. Primary lymphedema occurred in 28.2% (461). In the 71.8% (1176) with secondary CE cancer occurred in 72% (846) and 28% (330) due to other causes. Data showed that 84.2% (226) had full upper body mobility, 15.5% (41) had limited mobility and 0.2% (2) had lost all mobility. Lower limb mobility status: 90.4% (1205) complete mobility, 8.4% (112) reduced mobility and 1.2% (21) wheelchair bound. Concurrent leg ulceration occurred in 32.9% (322) with 3.1% (51) having antibiotics. Treatment patterns varied with only 32.4% (530) receiving instructions in skin care, 61.2% (1002) multilayer compression and a further 67.8% (1110) compression garment with 17.6% (288) having sequential pressure therapy. Only 1.4% (23) had received psychological support. Out of the total 481/1637 (29.4%) were not prescribed any
Lipedema is a common and complex disease whose accurate diagnosis remains elusive in many cases. Diagnostic ascertainment typically relies upon a compatible historical presentation, supported by physical findings. Diagnostic imaging has not always been helpful.
In the current issue of Lymphatic Research and Biology, Prof. Marina Cestari has provided insight into the applicability of three-dimensional ultrasound in this arena. The investigation entailed 40 subjects with lipedema or lipohypertrophy, representing a broad spectrum of stages and clinical patterns of the disease.
This descriptive study provides a first insight into the utility of the diagnostic modality in the tissue characterization of both adipose tissue and the fascial planes within the affected regions, highlighting the distinctive features that aggregate and distinguish lipohypertrophy and lipedema.
Characterization of the distinct biology of lipedema, along with description of appropriately sensitive and specific diagnostic techniques, will aid immeasurably in advancing our ability to care for this common and vexing form of human pathology.
Did the Masters of the past know the future? History and update of Italian Phlebolymphology’ - Articolo pubblicato su Veins and Lymphatics 04.09.2020
