Another form of hereditary lymphedema is Milroys disease caused by mutations in the VEGFR3 gene. Hereditary lymphedema is frequently syndromic and is associated with Turner syndrome, lymphedema–distichiasis syndrome, yellow nail syndrome, and Klippel–Trénaunay–Weber syndrome.One defined genetic cause for hereditary lymphedema is GATA2 deficiency. This deficiency is a grouping of several disorders caused by common defect, viz., familial or sporadic inactivating mutations in one of the two parental GATA2 genes. These autosomal dominant mutations cause a reduction, i.e. a haploinsufficiency, in the cellular levels of the genes product, GATA2. The GATA2 protein is a transcription factor critical for the embryonic development, maintenance, and functionality of blood-forming, lympathic-forming, and other tissue-forming stem cells. In consequence of these mutations, cellular levels of GATA2 are deficient and individuals develop over time hematological, immunological, lymphatic, and/or other disorders. GATA2 deficiency-induced defects in the lymphatic vessels and valves underlies the development of lymphedema which is primarily located in the lower extremities but may also occur in other places such as the face or testes (i.e. hydrocele). 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 the Emberger syndrome.Primary lymphedema has a quoted incidence of approximately 1-3 births out of every 10,000 births, with a particular female preponderance 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 Compared to secondary lymphedema, primary lymphedema is relatively rare.
The lymph ends its journey in the thoracic duct or right lymphatic duct, which drain into the blood circulation. Diagnosis
Diagnosis is generally based on signs and symptoms, with testing used to rule out other potential causes. An accurate diagnosis and staging may help with management. A swollen limb can result from different conditions that require different treatments. Diagnosis of lymphedema is currently based on history, physical exam, and limb measurements. Imaging studies such as lymphoscintigraphy and indocyanine green lymphography are only required when surgery is being considered. However, the ideal method for lymphedema staging to guide the most appropriate treatment is controversial because of several different proposed protocols. Lymphedema can occur in both the upper and lower extremities, and in some cases, the head and neck. Assessment of the extremities first begins with a visual inspection. Color, presence of hair, visible veins, size and any sores or ulcerations are noted. Lack of hair may indicate an arterial circulation problem. Given swelling, the extremities circumference is measured for reference as time continues. In early stages of lymphedema, elevating the limb may reduce or eliminate the swelling. Palpation of the wrist or ankle can determine the degree of swelling; assessment includes a check of the pulses. The axillary or inguinal nodes may be enlarged due to the swelling. Enlargement of the nodes lasting more than three weeks may indicate infection or other illnesses such as sequela from breast cancer surgery requiring further medical attention.Diagnosis or early detection of lymphedema is difficult.