Proteus syndrome

Last revised by Dalia Ibrahim on 26 Jan 2023

Proteus syndrome is a rare congenital, multisystemic, hamartomatous condition characterized by asymmetrical overgrowth of almost any part of the body and a broad spectrum of manifestations. It can affect tissue from any germinal layer.

Affected patients usually appear normal at birth and progressively develop abnormalities in childhood. The progression usually stops after adolescence 1. The highly variable clinical manifestations frequently lead to initial misdiagnosis 3.

Common clinical manifestations include:

  • cerebriform connective tissue nevus: especially suggestive if on the sole of the foot
  • epidermal nevus
  • disproportional overgrowth: hemihypertrophy/partial gigantism 
  • macrodactyly
  • dysregulation of adipose tissue: lipoma, regional absence of fat, overgrowth of fat in the posterior/anterior body wall or un subcutaneous fat of the extremities
  • vascular malformations: capillary, venous or lymphatic

Less common findings include 1:

Proteus syndrome is caused by sporadic mosaic mutations of a serine/threonine protein kinase encoded by the AKT1 gene; non-mosaic mutations are lethal. This enzyme is essential for normal cell growth hormone response. The genetic basis of the condition was elucidated in 2011 7,8

Radiographic features are not specific and refer to any clinical characteristics. However, characteristically, Proteus syndrome is considered when there is hemimegalencephaly, extensive lymphangitic or vascular malformations and asymmetric hemihypertrophy 1

Other radiographic features include enlarged and dysplastic vertebral bodies, scoliosis, cranial exostosis, osteomas, osteochondromas, enchondromas and genu valgum may also occur.

The diagnosis is either suspected on clinical grounds or with a combination of radiologic abnormalities.

Differential diagnosis is mostly done on a clinical basis since most of the clinical manifestations are not specific. However, the differential diagnosis includes:

The name of this syndrome comes from the Greek god of the sea Proteus who had the ability to change his shape to avoid capture, it was proposed by Wiedemann et al. in 1983. The name thus refers to the unpredictable asymmetric gigantism/hemihypertrophy associated with this disease. The first case report (1884) of this disease is credited to Sir Frederick Treves regarding his famous patient, Joseph Merrick (known as the "Elephant Man") 5,6.

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