Proteus Syndrome with Arteriovenous Malformation

Abstract

Proteus syndrome is a rare sporadic disorder that appears with localized macrosomia, congenital lipomatosis, and slow flow vascular malformations, connective tissue nevus, and epidermal nevus. There are usually some manifestations at birth. The vascular abnormalities that have been reported in Proteus syndrome are capillary and slow flow venous malformation. We report a case of a 10-year-old boy with confirmed Proteus syndrome characterized by high flow vascular malformation (arteriovenous [AV] malformation) unlike the usual vascular malformations seen in this syndrome. This case adds a new perspective to the established clinical findings of the Proteus syndrome.

SMAD4 Prevents Flow Induced Arteriovenous Malformations by Inhibiting Casein Kinase 2

“…Loss of function mutations in human PTEN cause Cowden syndrome, which is associated with tissue overgrowth and occasional AVMs. Gain of function mutations in PI3K is associated with venous malformations, while AKT-activating mutations cause Proteus syndrome which also leads to overgrowth of various tissues including the vasculature and occasional AVMs 46–48 , however these lesions are distinct from vascular lesions in HHT. In our experiments, we have found that Akt1 deletion did not prolong survival of the Smad4 mutant mice.…”

Cardiothoracic imaging findings of Proteus syndrome

“…Proteus syndrome is more common in males (male-to-female ratio of 2:1) and has an estimated prevalence of one per one million births 1 , 3 , 7 , 8 . Proteus syndrome is associated with a mosaic, somatic activating variant in AKT1 (typically c.49G >A p.Glu17Lys) which is an important aid in diagnosis 3 , 5 , 9 , 10 . However, due to the mosaic pattern of its heterogeneous manifestations, adherence to recently revised score-based diagnostic criteria for phenotypic features of Proteus syndrome is useful (Table 1 ) 9 , 11 .…”

“…Proteus syndrome is associated with a mosaic, somatic activating variant in AKT1 (typically c.49G >A p.Glu17Lys) which is an important aid in diagnosis 3 , 5 , 9 , 10 . However, due to the mosaic pattern of its heterogeneous manifestations, adherence to recently revised score-based diagnostic criteria for phenotypic features of Proteus syndrome is useful (Table 1 ) 9 , 11 . Proteus syndrome is defined as a score ≥ 10 points with an AKT1 pathogenic variant or a score of ≥ 15 points without the AKT1 variant.…”

“…Proteus syndrome is defined as a score ≥ 10 points with an AKT1 pathogenic variant or a score of ≥ 15 points without the AKT1 variant. Individuals who carry AKT1 pathogenic variant and score 2–9 based on the revised diagnostic criteria are classified as AKT1 -related overgrowth spectrum 9 .…”