Primary lymphoedema

Brouillard, Pascal; Witte, Marlys H.; Erickson, Robert P.; Damstra, Robert J.; Becker, C.; Quéré, I.; Vikkula, Miikka

doi:10.1038/s41572-021-00309-7

Cited by 52 publications

(50 citation statements)

References 253 publications

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“…Sufficient information is not available on causative genetic variants for primary lymphedema, warranting additional studies investigating the involvement of unknown candidate genes. In addition, although the samples and targeted gene sequencing results indicated novel findings regarding the Asian primary lymphedema population, owing to the limitations of performing a nationwide genetic study, there remain other genes that should be investigated for pathogenic variants 17 . Variants in these genes can account for cases of primary lymphedema, and these genes must be investigated in the near future.…”

Section: Discussionmentioning

confidence: 99%

Clinical staging and genetic profiling of Korean patients with primary lymphedema using targeted gene sequencing

Seo

Lee

Park

et al. 2022

Sci Rep

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Lymphedema is a progressive disease caused by lymphatic flow blockage in the lymphatic pathway. Primary (hereditary) lymphedema is caused by genetic mutations without secondary causes. We performed clinical profiling on Korean primary lymphedema patients based on their phenotypes using lymphoscintigraphy and made genetic diagnoses using a next-generation sequencing panel consisting of 60 genes known to be related to primary lymphedema and vascular anomalies. Of 27 patients included in this study, 14.8% of the patients had lymphedema of the upper extremities, 77.8% had lymphedema of the lower extremities and 7.4% had 4-limbs lymphedema. Based on the International Society of Lymphology staging, 14, 10, and 3 patients had stage 3, 2, and 1 lymphedema, respectively. Only one family was genetically confirmed to harbor likely pathogenic variants in CELSR1. The proband was carrying two likely pathogenic variants in CELSR1, while her symptomatic mother was confirmed to carry only one of the variants. Furthermore, two other variants of uncertain significance in CELSR1 were detected in other patients, making CELSR1 the most commonly altered gene in our study. The clinical and genetic profile of hereditary lymphedema reported here is the first such data series reported for South Korea.

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Section: Discussionmentioning

confidence: 99%

Clinical staging and genetic profiling of Korean patients with primary lymphedema using targeted gene sequencing

Seo

Lee

Park

et al. 2022

Sci Rep

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“…The development of primary lymphedema is likely due to altered genetics, but only around one-third of all cases have a known mutation [ 110 ]. Known mutations that lead to primary lymphedema, often identified and characterized through familial segregation analyses, can be autosomal dominant or autosomal recessive.…”

Section: Genetic Causes or Indicatorsmentioning

confidence: 99%

“…All result in some degree of lymphatic insufficiency and lymphedema in both human and genetic murine models. These mutations have been elegantly compiled and reviewed elsewhere, with a few noteworthy selections provided here: [ 1 , 110 , 111 ].…”

Section: Genetic Causes or Indicatorsmentioning

confidence: 99%

Current Mechanistic Understandings of Lymphedema and Lipedema: Tales of Fluid, Fat, and Fibrosis

Duhon¹,

Phan²,

Taylor

et al. 2022

IJMS

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Lymphedema and lipedema are complex diseases. While the external presentation of swollen legs in lower-extremity lymphedema and lipedema appear similar, current mechanistic understandings of these diseases indicate unique aspects of their underlying pathophysiology. They share certain clinical features, such as fluid (edema), fat (adipose expansion), and fibrosis (extracellular matrix remodeling). Yet, these diverge on their time course and known molecular regulators of pathophysiology and genetics. This divergence likely indicates a unique route leading to interstitial fluid accumulation and subsequent inflammation in lymphedema versus lipedema. Identifying disease mechanisms that are causal and which are merely indicative of the condition is far more explored in lymphedema than in lipedema. In primary lymphedema, discoveries of genetic mutations link molecular markers to mechanisms of lymphatic disease. Much work remains in this area towards better risk assessment of secondary lymphedema and the hopeful discovery of validated genetic diagnostics for lipedema. The purpose of this review is to expose the distinct and shared (i) clinical criteria and symptomatology, (ii) molecular regulators and pathophysiology, and (iii) genetic markers of lymphedema and lipedema to help inform future research in this field.

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“…Lymphatic vessels may be aplastic or hypoplastic, have valvular insufficiency, or have disruptions and decreased contractility. PL can present as an isolated condition or part of a syndrome and is classified based on the age of onset, pattern, and associated features 7,8 . Infant‐onset occurs in the first year of life, childhood‐onset age 1–12 years, adolescent‐onset age 13–21, and adult‐onset after 21 years of age.…”

Section: Defining Lymphedema Versus Other Types Of “Swelling”mentioning

confidence: 99%

How we approach lymphedema in the pediatric population

Pateva

Greene

Snyder

2022

Pediatric Blood & Cancer

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Lymphedema in children is rare; however, it is usually a progressive and chronic condition. Accurate diagnosis of lymphedema in the pediatric population often takes several months and sometimes is delayed for years. Lymphedema can be isolated or associated with genetic syndromes, thus it is very important to identify the correct diagnosis, to select carefully which patients to refer for genetic testing, and to initiate appropriate treatment in a timely fashion. In this article, we review key information about diagnosis of lymphedema, associated conditions and syndromes, and current treatment modalities.

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Primary lymphoedema

Cited by 52 publications

References 253 publications

Clinical staging and genetic profiling of Korean patients with primary lymphedema using targeted gene sequencing

Clinical staging and genetic profiling of Korean patients with primary lymphedema using targeted gene sequencing

Current Mechanistic Understandings of Lymphedema and Lipedema: Tales of Fluid, Fat, and Fibrosis

How we approach lymphedema in the pediatric population

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