1999-05-06-21 Klippel-Trenaunay-Weber syndrome © Jeanty www.thefetus.net/
Updated 2006-01-18 by Juliana Leite, MD
Original text 1999-05-06 Philippe Jeanty, MD, PhD & Sandra R Silva, MD
Synonyms: Klippel-Trenaunay syndrome, Angioosteohypertrophy syndrome
Definition: In 1990, Klippel and Trenaunay originally described the entity of limb overgrowth, multiple cutaneous angiomata and varicose veins, which was confirmed by Parkes-Weber in 1918 and extended by the infrequent finding of arteriovenous fistulae. This syndrome is a rare congenital soft tissue anomaly, with sporadic occurrence, characterized by a triad of multiple hemangiomas, arteriovenous fistulas and unilateral limb hypertrophy, due to bony and soft tissue overgrowth.
Etiology: Happle suggested a paradominant inheritance most satisfactorily explains the findings. Heterozygous individuals for a single gene defect are phenotypically normal. The trait is only expressed when a somatic mutation occurs in the normal allele at an early stage of embryogenesis. The embryo is then a mosaic of homozygous or heterozygous cell lines for the mutation. This explains the patchy distribution of the defect.
Recurrence risk: Probably none, although some cases have raised the possibility of autosomal dominance.
Diagnosis: These may include hydrops fetalis (from high output cardiac failure) with limbs edema and hypertrophy (fig. 3) (more girth then length), ascites, abnormal abdominal hemangiomatous masses (figs 1-2), and hepatomegaly,. A beautiful 3D diagnosis was made recently.
Figure 1: Cross-section at the level of the lower abdomen. Note the multicystic irregular and ill-defined masses.
Figure 2: Cross-section at the level of the lower abdomen. Note the multicystic irregular and ill-defined masses.
Figure 3: A large shell of soft-tissue encompasses the thigh. The contra-lateral thigh was normal.
Pathogenesis: The exact mechanism causing Klippel-Trenaunay-Weber syndrome is not known. A mesodermal defects affecting angiogenesis and associated with persistent of the embryonic vascular network might explain the vascular anomalies. Others have suggested that a disturbance in the regulation of tissue growth factors is the underlying mechanism.
Genetic anomaly: This may be due to a single gene defect on either chromosome 5q or p11.
Associated anomalies: Kasabach-Merritt syndrome of thrombocytopenia due to platelet consumption within the hemangioma and high output cardiac failure may complicate the outcome.
Differential diagnosis: Lymphangioma, Proteus syndrome and fetal thoracic mass (even if color flow Doppler studies of the mass are negative).
Prognosis: When detected prenatally the disorder is usually more severe and the prognosis poor when associated with cardiac insufficiency.
Management: Termination of pregnancy can be offered in the severe forms; otherwise, no alteration of management is expected. Given the rarity of the disease, there isn’t enough information available to counsel patients regarding obstetric outcome.
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