Primary or secondary disorder of lymphatic drainage.
Hereditary Lymphedema Type I (Nonne-Milroy Syndrome; Milroy Syndrome; Congenital Hereditary Lymphedema
type): Present at birth with areas of swelling. The importance of the
swelling tends to increase with age, especially during infancy.
Hereditary Lymphedema Type II (Meige Lymphedema; Familial Lymphedema Praecox; Hereditary Lymphedema
Tarda): Usually develops during childhood, adolescence, or early adulthood.
It produces severe swelling in areas below the waist. It usually includes
red skin over areas of swelling and associated discomfort and/or
Secondary Lymphedema: Results from inadequate lymphatic drainage as a result of various causes,
such as surgery, recurrent lymphangitis, cellulitis, neoplastic invasion of
lymphatics, fibrosis following radiotherapy, or scar formation.
Incidence for hereditary lymphedema is estimated at
1:10,000 individuals. However, the incidence for secondary lymphedema is
significantly higher. Meige lymphedema represents 80% of all hereditary
Hereditary lymphedemas that are not associated
with other malformations usually affect the lower limbs and are inherited as
an autosomal dominant trait with variable penetrance (autosomal or
sex-linked recessive forms are less common). These nonsyndromic hereditary
lymphedemas are categorized by their age of onset, being either congenital
(Milroy disease) or having an onset in childhood or around puberty (Meige
disease). Lymphedema can been associated with various other anomalies, many
of which are genetic (autosomal recessive, autosomal dominant or X-linked
recessive inheritance), and with Turner and Noonan syndromes.
Several genes may be involved in the development of hereditary lymphedema,
including the following:
Vascular endothelial growth factor receptor 3 (VEGFR3), formerly known
as FLT4, is located on chromosome 5.
FOXC2, which is responsible for causing the lymphedema-distichiasis syndrome
At least one (more likely, several) other gene can be responsible for other
forms of hereditary lymphedema.
In the primary forms, aplasia or hypoplasia of the
lymphatic vessels results in dilatation of extralymphatic spaces. In both
primary and secondary forms, lymphatic obstruction from any cause results in
increased protein content of the extravascular tissue and, because of its
osmotic effect, retention of additional water. This excess extravascular
protein often leads to proliferation of fibroblasts and organization of the
edema fluid, giving rise to a characteristic firm, nonpitting swelling.
Clinical findings, results of the patent blue test and
fluorescence microlymphography, indirect lymphography, or isotope studies
suffice for correct diagnosis. In hereditary lymphedema present at birth
(Milroy disease), the lymphatic capillaries and precollectors are aplastic,
whereas in sporadic lymphedema with postpubertal onset, the large collectors
are hypoplastic or aplastic, and a well-developed superficial capillary
network is detected.
The edema in Milroy disease is present from birth
in contrast to the edema, particularly severe below the waist, that develops
around puberty in Meige syndrome. Involvement of the upper limbs, face, and
larynx are notable features in Meige syndrome. There is also an association
with deafness, cleft palate, primary ...