BACKGROUND Proteus syndrome is a rare congenital disorder with progressive asymetric overgrowth of multiple tissues. OBJECTIVES To determine the range of cutaneous findings in Proteus syndrome and to correlate cutaneous findings with overall disease severity. DESIGN A prospective cohort study was performed at the National Institutes of Health, a tertiary referral center. PATIENTS Twenty-f...

BACKGROUND The diagnostic criteria of Proteus syndrome include various lesions of localized overgrowth such as digital gigantism, hemihyperplasia with unilateral macrocephaly, epidermal nevus, and mesodermal hamartomas such as lipoma, lymphangioma, hemangioma, or fibroma. Hyperplasia of the plantar dermal tissue may result in a characteristic cerebriform appearance. However, hypoplastic lesions...

Joseph Carey Merrick, better known as the “Elephant Man,” suffered from an extreme condition initially diagnosed as Neurofibromatosis I. Recent research, however, has challenged that view and has attributed his massive disfigurement to the effects of Proteus syndrome, one of the most debilitating and ravaging diseases known to man. An analysis of the data and pathology from Merrick’s records, c...

Proteus syndrome is a complex hamartomatous disorder characterized by multiple, diverse, somatic manifestations. We present a case in which severe, evolving CNS abnormalities were also exhibited. Imaging findings at presentation included hemimegalencephaly, subependymal calcified nodules, and periventricular cysts. Subsequently, dural sinus thrombosis developed. Eight previously reported patien...

A 15-year-old girl developed a progressive paraparesis over a period of six months, secondary to spinal cord compression by a lipomatous mass and anomalies of the vertebral column. Clinically, a right hemihyperplasia affecting the trunk and lower limb was evident, as well as a right convex lumbar scoliosis. CT and MRI demonstrated severe spinal cord compression resulting from intraspinal lipoma...

A somatic activating mutation in AKT1, c.49G>A, pGlu17Lys, that results in elevated AKT signaling in mutation-positive cells, is responsible for the mosaic overgrowth condition, Proteus syndrome. ARQ 092 is an allosteric pan-AKT inhibitor under development for treatment in cancer. We tested the efficacy of this drug for suppressing AKT signaling in cells and tissues from patients with Proteus s...

I N THIS ISSUE OF THE ARCHIVES, NGUYEN AND COLleagues present a clinically oriented study of 24 consecutive patients with Proteus syndrome who were evaluated at the National Institutes of Health in Bethesda, Md. The diagnostic criteria of Proteus syndrome proposed by an international working group some years ago were met in all cases. Because this multisystem birth defect occurs rarely, an anal...