Rare Diseases Symptoms Automatic Extraction

Monozygotic twins discordant for vascular malformations and dysregulated growth.

[proteus syndrome]

There is a large group of disorders characterized by non-cranial vascular malformations and a dysregulated growth, of which the prototype may be Klippel-Trenaunay syndrome (KTS). The aetiology of KTS and vascular malformations-dysregulated growth (VM-DG) syndromes resembling KTS is obscure, but polygenic paradominant inheritance involving mutations or polymorphisms in two or more genes simultaneously, of which one (or more) are involved in (lymph)angiogenesis and the other(s) in growth regulation has been proposed for KTS and related VM-DG entities. This provides an explanation for the variability of the VM-DG syndromes through the numerous possible combinations of mutated genes involved. We report on three monozygotic female twins who are discordant for a VM-DG syndrome resembling KTS. We suggest that our observation is consistent with the concept of polygenic paradominant inheritance involving two or more genes. We discuss the published observations in twins discordant for other disorders associated with disturbed growth regulation such as Beckwith-Wiedemann syndrome and Silver-Russell syndrome, and the occurrence in cousins with KTS and Beckwith-Wiedemann syndrome, which are best explained by an imprinting disturbance. We propose that, similarly, disturbed imprinting plays a role in the pathogenesis of VM-DG syndromes in general, and suggest the same may hold for KTS in sensu strictu or Proteus syndrome. Further studies to investigate imprinting status in VM-DG syndromes, including KTS and Proteus syndrome, are warranted.