Heron Werner, MD*, Pedro Daltro, MD*, Dorothy Bulas, MD#
* Clínica de Diagnóstico por Imagem (CDPI) & Instituto Fernandes Figueira (IFF) – FIOCRUZ – Rio de Janeiro – Brazil
# Professor of Radiology and Pediatrics – Children"s National Medical Center – George Washington University Medical Center – 111 Michigan Ave, NW, Washington D.C. 20010
Hereditary or primary lymphedema, first described by Milroy in 1892, is a developmental disorder of the lymphatic system which leads to a disabling and disfiguring swelling of the extremities (1,2). Despite having been described over a hundred years ago, little is still known about the developmental regulation of the lymphatic system, and little progress has been made in understanding the mechanisms causing lymphedema.
The lymphatic system is a complex structure organized in a parallel fashion to the circulatory system. In contrast to the circulatory system, which utilizes the heart to pump blood throughout the body, the lymphatic system must pump lymph fluid by using the inherent contractile of the lymphatic vessels. Present in one or both legs, the lymphedema persists throughout life but does not seem to affect longevity. As the patient grows up, the overlying skin displays a slightly rosy hue, while the size of the edematous parts remains proportional to the remainder of the body. It rarely presents a genital edema, what resembles sexual ambiguity (6).
Hereditary lymphedema generally shows an autosomal dominant pattern of inheritance with reduced penetrance, variable expression and variable age at onset. The gene mutation has been found at chromosome 5q34-q35, although there is also some evidence of two differents sub-mutations (2). Its incidence is around 1:33,000 newborns (male to female ratio 1:2,3) (1). Swelling may appear in one or all limbs. It can vary in degree and distribution, and, if untreated, may worsen with time. In some rare cases, angiosarcoma may develop in affected tissues (3).
The differential diagnosis is carried out with non-lymphatic edema, Noonan syndrome, Turner syndrome, Meige lymphedema (hereditary lymphedema type II) and congenital recessive type lymphedema (7). Complications are rare, but can sometimes be reported as intestinal lymphangiectasia, recurrent septic arthritis (8), bacterial infections of dorsal aspects of feet and toes, angiosarcoma (3) and lymphangiosarcoma (9).
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Ferrell RE, Levinson KL, Esman JH, Kimak MA, Lawrence EC, Barmada MM, Finegold DN. Hereditary lymphedema: evidence for linkage and genetic heterogeneity. Hum Mol Genet 1998 Dec;7(13):2073-8.
Offori TW, Platt CC, Stephens M, Hopkinson GB. Angiosarcoma in congenital hereditary lymphoedema (Milroy’s disease) diagnostic beacons and a review of the literature. Clin Exp Dermatol 1993 Mar;18(2):174-7.
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Pfister G, Saesseli B, Hoffmann U, Geiger M, Bollinger A. Diameters of lymphatic capillaries in patients with different forms of primary lymphedema. Lymphology 1990 Sep;23(3):140-4.
Sarda P, Jalaguier J, Montoya F, Bonnet H. Hereditary congenital lymphedema with pseudosexual ambiguity. J Genet Hum 1988 Aug;36(4):353-60.
Wheeler ES, Chan V, Wassman R, Rimoin DL, Lesavoy MA. Familial lymphedema praecox: Meige’s disease. Plast Reconstr Surg 1981 Mar; 67(3):362-4.
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Brostrom LA, Nilsonne U, Kronberg M, Soderberg G. Lymphangiosarcoma in chronic hereditary oedema (Milroy’s disease). Ann Chir Gynaecol 1989;78(4):320-3.