Editing Lymphedema (section)

===At birth===
'''Hereditary lymphedema''' is a primary lymphedema – swelling that results from abnormalities in the [[lymphatic system]] that are [[congenital|present from birth]]. Swelling may be present in a single limb, several limbs, genitalia, or the face. It is sometimes diagnosed prenatally by a [[nuchal scan]] or postnatally by [[:wikt:lymphoscintigraphy|lymphoscintigraphy]].{{medical citation needed|date=September 2023}}

The most common cause is [[Meige disease]] which usually presents at [[puberty]]. Another form of hereditary lymphedema is [[Milroy's disease]], caused by mutations in the [[VEGFR3]] gene.<ref name="grada-2017" /><ref>{{Cite book |chapter-url=http://accessmedicine.mhmedical.com/content.aspx?aid=5014541|title=Schwartz's Principles of Surgery |last1=Liem |first1=Timothy K. |last2=Moneta |first2=Gregory L. |date=2010 |publisher=The McGraw-Hill Companies |editor-last=Brunicardi |editor-first=F. Charle s|edition=9th |location=New York, NY|editor-last2=Andersen|editor-first2=Dana K.|editor-last3=Billiar|editor-first3=Timothy R.|editor-last4=Dunn|editor-first4=David L.|editor-last5=Hunter|editor-first5=John G.|editor-last6=Matthews|editor-first6=Jeffrey B.|editor-last7=Pollock|editor-first7=Raphael E.|chapter=Chapter 24. Venous and Lymphatic Disease}}{{Dead link|date=January 2019 |bot=InternetArchiveBot |fix-attempted=yes}}</ref> Hereditary lymphedema is frequently syndromic and is associated with [[Turner syndrome]], [[lymphedema–distichiasis syndrome]], [[yellow nail syndrome]], and [[Klippel–Trénaunay syndrome]].<ref>{{Cite book|chapter-url=http://accessmedicine.mhmedical.com/content.aspx?aid=56081150|title=Fitzpatrick's Dermatology in General Medicine|last1=Burkhart|first1=Craig N.|last2=Adigun|first2=Chris|last3=Burton|first3=Claude S. |date=2012|publisher=The McGraw-Hill Companies|editor-last=Goldsmith|editor-first=Lowell A.|edition=8|location=New York, NY|editor-last2=Katz|editor-first2=Stephen I.|editor-last3=Gilchrest|editor-first3=Barbara A.|editor-last4=Paller|editor-first4=Amy S.|editor-last5=Leffell|editor-first5=David J.|editor-last6=Wolff|editor-first6=Klaus|chapter=Chapter 174. Cutaneous Changes in Peripheral Venous and Lymphatic Insufficiency}}{{Dead link|date=January 2019 |bot=InternetArchiveBot |fix-attempted=yes}}</ref>

One defined genetic cause for hereditary lymphedema is [[GATA2 deficiency]]. This deficiency is a grouping of several disorders caused by a single defect: familial or sporadic [[Mutation#By effect on function|inactivating mutation]]s in one of the two parental ''[[GATA2]]'' [[gene]]s. These [[autosomal dominant]] mutations cause a reduction, i.e. a [[haploinsufficiency]], in the cellular levels of the gene's product, [[GATA2]]. The GATA2 [[protein]] is a [[transcription factor]] critical for the [[Embryogenesis|development]], maintenance, and functionality of [[blood|blood-forming]], [[Lymphatic system|lymphatic-forming]], and other tissue-forming [[stem cell]]s. Due to these mutations cellular levels of GATA2 are deficient and over time individuals develop hematological, immunological, lymphatic, and other disorders. GATA2 deficiency-induced defects in the lymphatic vessels and valves underlies the development of lymphedema, primarily in the lower extremities but may also occur in places such as the face or [[hydrocele testis|testes]]. This form of the deficiency, when coupled with [[sensorineural hearing loss]], which may also be due to faulty development of the lymphatic system, is sometimes termed [[Emberger syndrome]].<ref>{{cite journal | vauthors = Crispino JD, Horwitz MS | title = GATA factor mutations in hematologic disease | journal = Blood | volume = 129 | issue = 15 | pages = 2103–2110 | date = April 2017 | pmid = 28179280 | pmc = 5391620 | doi = 10.1182/blood-2016-09-687889}}</ref><ref>{{cite journal | vauthors = Hirabayashi S, Wlodarski MW, Kozyra E, Niemeyer CM | title = Heterogeneity of GATA2-related myeloid neoplasms | journal = International Journal of Hematology | volume = 106 | issue = 2 | pages = 175–182 | date = August 2017 | pmid = 28643018 | doi = 10.1007/s12185-017-2285-2 | doi-access = free}}</ref>

Primary lymphedema occurs in approximately one to three births out of every 10,000 births, with a female to male ratio of 3.5:1. In North America, the incidence of primary lymphedema is approximately 1.15 births out of every 100,000 births.{{Contradictory inline|date=September 2023}} Compared to secondary lymphedema, primary lymphedema is relatively rare.<ref>{{cite journal | vauthors = Kurland LT, Molgaard CA | title = The patient record in epidemiology | journal = Scientific American | volume = 245 | issue = 4 | pages = 54–63 | date = October 1981 | pmid = 7027437 | doi = 10.1038/scientificamerican1081-54 | bibcode = 1981SciAm.245d..54K}}</ref>