Milroy Disease

Wed, 02/20/13 - 13:29

Authors:
ALEXANDER K. C. LEUNG, MD
University of Calgary
HARDALLY R. HEGDE, MD
Alberta Childrens Hospital
Deepak M. Kamat, MD, PhDSeries Editor: Dr Kamat is professor of pediatrics at Wayne State University in
Detroit. He is also director of the Institute of Medical Education and vice chair of education at Childrens Hospital of
Michigan, both in Detroit.

A male infant was delivered at term to a 24-year-old woman (gravida 3, para 1). The pregnancy had been
uncomplicated; the vaginal delivery was normal. Apgar scores were 7 at 1 minute and 9 at 5 minutes. Birth weight
was 3020 g (6 lb 11 oz); length, 51 cm (20 in); and head circumference, 36 cm (14 in).
Nonpitting edema of both feet was noted at birth; all other physical examination findings were normal. A review of the
family history revealed that the childs father and paternal grandfather had lymphedema of both feet at birth.
Milroy disease was diagnosed. This is an autosomal dominant inherited form of lymphedema, with onset at or near
birth.
Inadequate lymphatic drainage that causes lymphedema may be attributed to congenital lymphatic hypoplasia or to
structural damage to lymphatic vessels. Congenital lymphatic hypoplasia is associated with Milroy disease, Turner
syndrome, Noonan syndrome, yellow nail syndrome, lymphedema praecox, and distichiasis. Damage to the
lymphatic vessels can occur from surgery, trauma, neoplasms, radiation therapy, and chronic lymphangitis caused by
filariasis or lymphogranuloma venereum.
There is no specific therapy for Milroy disease. Affected limbs should be elevated whenever possible. If skin sepsis
occurs, prompt treatment is necessary to prevent further lymphatic insufficiency. Over time, fibrosis develops in the
interstitial tissues and the skin may become thickened and pigmented. Skin ulcers can occur at sites of pressure.
FOR MORE INFORMATION:
Leung AK, Robson WL. Oedema in childhood. J R Soc Health. 2000;120:212-219.



Milroy Disease.
Authors
Brice GW, Mansour S, Ostergaard P, Connell F, Jeffery S, Mortimer P.
Editors
In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong CT, Smith RJH, Stephens K, editors.
Source
GeneReviews

[Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.

2006 Apr 27 [updated 2009 Jul 23].
Excerpt
DISEASE CHARACTERISTICS:
Milroy disease is characterized by lower-limb lymphedema, present at birth as pedal edema or developing
soon after. Occasionally it develops later in life. The severity of edema shows both inter- and intrafamilial
variability. Swelling is usually bilateral but can be asymmetric. The degree of edema can progress but in
some instances can improve, particularly in early years. Other features sometimes associated with Milroy
disease include hydrocele (37% of males), prominent veins (23%), upslanting toenails (14%),
papillomatosis (10%), and urethral abnormalities in males (4%). Cellulitis, which can damage the
lymphatic vessels, occurs in approximately 20% of affected individuals, with infection significantly more
likely in males than females.
DIAGNOSIS/TESTING:
Milroy disease is diagnosed by clinical findings and confirmed by molecular genetic testing.
Lymphoscintigraphy can be performed; the characteristic finding is lack of uptake of radioactive colloid in
the ilioinguinal lymph nodes caused by a paucity of lymphatic vessels or abnormal function of the vessels
in the lower limbs. FLT4 (VEGFR3) is the only gene known to be associated with Milroy disease.
MANAGEMENT:
Treatment of manifestations: A lymphedema therapist may utilize fitted stockings and massage to
improve the cosmetic appearance or decrease the size of the limb and reduce the risk of complications.
Improvement in swelling is usually possible with use of properly fitted compression hosiery and/or
bandaging. Prevention of secondary complications: Frequency of cellulitis can be reduced through good
skin hygiene, prompt treatment of infections with antibiotics, and prophylactic antibiotics for recurrent
episodes. Agents/circumstances to avoid: wounds to limbs; long periods of immobility with the legs in a
dependent position; and medications that can cause increased leg swelling. Evaluation of relatives at risk:
Evaluating relatives at risk ensures identification of those who will benefit from treatment early in the
disease course.
GENETIC COUNSELING:
Milroy disease is inherited in an autosomal dominant manner. Each child of an individual with Milroy
disease has a 50% chance of inheriting the mutation. The proportion of cases caused by de novo
mutations is not known. Ultrasonography in the third trimester of pregnancy may detect swelling of the
dorsum of the feet and more extensive edematous states in an affected fetus. Prenatal testing is possible
for pregnancies at increased risk if the disease-causing mutation in the family is known; however, it is
rarely requested.
Copyright 1993-2014, University of Washington, Seattle. All rights reserved.