Overgrowth syndromes with complex vascular anomalies

https://doi.org/10.1053/j.sempedsurg.2014.06.013Get rights and content

Abstract

Management of overgrowth syndromes with complex vascular anomalies is challenging. Careful analysis of the various clinical features by an interdisciplinary team of physicians experienced in this field is paramount to proper diagnostic and therapeutic approaches. In this article, we focus on the spectrum of the clinical presentation and the management strategies of the most common overgrowth syndromes with complex vascular anomalies.

Introduction

Proper diagnosis of complex and syndromic vascular anomalies can be challenging mostly because of the overlapping clinical appearance and their relative rarity. The vascular component of these syndromes is typically associated with other soft tissue (such as adipose and fibro-adipose tissue) and skeletal overgrowth and anomalies. The etiology of resulting symptoms, primarily pain and functional impairment, is also multifactorial and can be difficult to characterize and manage.1, 2

Careful analysis of the clinical features and the use of proper nosology are essential for the management of these disorders. Treatment of vascular anomalies and syndromes requires an interdisciplinary team of physicians with experience in overgrowth and vascular anomalies. This article reviews the wide spectrum of clinical presentation and management strategies of the most frequently encountered overgrowth syndromes with complex vascular anomalies at specialized vascular anomalies centers.

Section snippets

Classification of overgrowth syndromes with complex vascular anomalies

Overgrowth syndromes with complex vascular anomalies encompass a myriad of very heterogeneous group of disorders, many of which present with similar clinical features. In addition, these conditions are predisposed by diverse etiologies, many of which have not been deciphered yet. Accordingly, classification and analysis of these disorders based on a common denominator is particularly challenging and can be rather arbitrary.

Recent major advances in the genetics of various overgrowth syndromes

Klippel–Trenaunay Syndrome (KTS)

Klippel–Trenaunay syndrome (KTS) (OMIM # 149000) represents the prototype of complex overgrowth syndromes associated with vascular anomalies. KTS comprises capillary, lymphatic, and venous malformations of the limb with overgrowth and affects the lower extremity in the vast majority of patients.6 Soft tissue overgrowth is predominantly fatty and located primarily in the extrafascial/subcutaneous compartment. Osseous overgrowth of the extremity typically follows the soft tissue. KTS

CLOVES syndrome

Congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal anomalies (CLOVES) syndrome is a recently recognized clinical entity, although Hermann Friedberg published in 1867 a report on a patient who likely had CLOVES.16

The key feature of this syndrome is a truncal lipomatous mass of variable size that is noted at birth. The truncal lipomatous masses may contain a variable portion of lymphatic malformation (Figure 3A). The fatty growths often extend from the trunk

Fibro-adipose vascular anomaly (FAVA)

Fibro-adipose vascular anomaly (FAVA) is a newly recognized complex mesenchymal malformation.2 Its main features are solid fibrofatty replacement of the affected muscle and slow-flow vascular malformations. The calf (the gastrocnemius and soleus muscles) and the forearm are the most affected areas. Phlebectasia is the typical venous component, which is located in the affected muscle or the adjacent subcutis. Phlebectasia may affect the orthotopic major veins or smaller local or anomalous veins.

Parkes Weber syndrome/Capillary–Arteriovenous Malformation (CM-AVM)

Parkes Weber syndrome combines soft tissue and/or bony hypertrophy, pink cutaneous stain, and underlying diffuse hypervascularity of the affected extremity (Figure 5A and B). The bony hypertrophy results often in a limb-length discrepancy. The increased flow usually results in warmer limb. Parkes Weber syndrome is rather a specific manifestation of capillary–arteriovenous malformation (CM-AVM) disorders caused by mutations in the RASA1 gene.5 Correct diagnosis is essential since patients with

PTEN hamartoma tumor syndrome (PTHS)

PTEN hamartoma tumor syndrome (PHTS) encompasses a group of syndromes associated with germline mutations in the tumor suppressor PTEN (Cowden syndrome (CS) and Bannayan–Riley–Ruvalcaba syndrome (BRRS)). PTEN, phosphatase and tensin homolog gene on chromosome 10, encodes a tumor suppressor that antagonizes the phosphatidylinositol 3-kinase (PI3K/AKT) and thus down-regulates the PI3K/AKT pathway resulting in cell-cycle arrest and/or apoptosis.22, 23

In the past, these allelic disorders were

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