What causes congenital lymphedema?

Updated: Mar 24, 2021
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD  more...
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Congenital lymphedema, or Milroy disease, accounts for 10-25% of all primary lymphedema cases. A familial, autosomal-dominant disorder, it is often caused by anaplastic lymphatic channels. The disorder manifests at birth or later, up to age 1 year. Females are affected twice as often as males, and the lower extremities are involved 3 times more frequently than the upper extremities. The edema is most commonly pitting and nonpainful. Patients may have bilateral lymphedema, and this form may improve spontaneously with increasing age. Unilateral lymphedema is not noted in Milroy disease, but if it were, it might spontaneously improve with age.

Congenital lymphedema has also been associated with cellulitis, prominent veins, intestinal lymphangiectasias, upturned toenails, and hydrocele.

Although congenital lymphedema is classically thought to be caused by the failure of lymphatic vessels to develop in utero, examination of patients with this disease by fluorescence microlymphangiography demonstrated a high rate of functional failure of the lymphatic system. [13, 14] Such failure may play a role in the development of edema.

Congenital lymphedema may be linked to a mutation that inactivates VEGFR3. This gene, which is expressed in adult lymphatic endothelial cells, has been mapped to the telomeric part of chromosome arm 5q in the region 5q34-q35. This region codes for a tyrosine kinase receptor specific for the function of the lymphatic vessels, and indeed, the receptor has been reported to be abnormally phosphorylated in patients with Milroy disease. [15, 16, 17, 18, 19, 20, 21]

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