The Etiology of the Klippel- Trenaunay Syndrome

Klippel-Trenaunay Syndrome and Spinal Arteriovenous Malformations: An Erroneous Association

“…31 Unlike the Parkes Weber syndrome, arteriovenous communications are not a feature of KTS. 32,33 Unfortunately, KTS has often been used as a generic diagnosis referring to a heterogeneous group of vascular anomalies with overgrowth.…”

“…32 Happle 42 proposed the more intriguing theory of paradominant inheritance, in which individuals heterozygous for the mutation would have no symptoms and the mutation could be transmitted unperceived through many generations. The phenotype would only manifest when an additional postzygotic mutation occurs, giving rise to loss of the corresponding wildtype allele, resulting in a cellular clone, either homozygous or hemizygous for the mutation.…”

A Case of Klippel Trenaunay Syndrome

“…Although the cause of KTS is still unknown, it is hypothesized that it is caused by a mesodermal abnormality during foetal development leading to vascular and soft tissue malformations in the affected limb. 8 McGrory and Amadio. 9 believed that an underlying mixed mesodermal and ectodermal dysplasia was responsible for development of KTWS.…”

Klippel Trenaunay Syndrome, Inverse Klippel Trenaunay Syndrome: Hypertrophy of Lower Limbs and Atrophy of the Upper Limbs and Facial Muscles: Case Report and Literature Review

“…However, in some cases, clinical manifestations of the syndrome have been found in family members, suggesting an autosomal dominant inheritance [16]. The presumed pathogenetic pathway is that of mesodermal developmental derangement, leading to maintenance of microscopic arteriovenous communications in the limb bud, with consequent development of the naeuvs, superficial varices, and limb hypertrophy [17]. Several hypotheses regarding cause and pathogenesis in KTS exist, but none explains the full characteristics of KTS.…”

“…Servelle's theory stated that there is a primary obstruction of the venous system resulting in venous hypertension and thus development of abnormal venous pathways and tissue overgrowth [19]. Also, maintenance of microscopic arteriovenous communication in the limb bud vein had been proposed [17]. Others suggested alteration of the balance between angiogenesis and vasculogenesis, a process that is controlled by numerous genes [20].…”