Proteus syndrome

Proteus syndrome is a rare congenital, multisystemic, hamartomatous condition characterized by asymmetrical overgrowth of almost any part of body and a wide spectrum of manifestations. It can affect tissue from any germinal layer. It is suspected to be a genetic condition, but the specific gene isn't currently identified.

Clinical presentation

Affected patients usually appear normal at birth and progressively develop abnormalities in chilhood. 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 naevus: virtually pathognomonic
• epidermal naevus
• disproportional overgrowth: hemihypertrophy /partial gigantism 
  • limbs
  • vertebrae
  • calvarial thickening
  • rarely: external auditory meatus, viscera (spleen, kidney, thymus)
• 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 include¹:

• bilateral ovarian cystadenomas
• parotid monomorphic adenoma
• abnormal facial features: dolichocephaly, low nasal bridge, anteverted nares, etc...

Radiographic features

Radiographic features are not specific and refers to any clinical features. However, characteristically, Proteus syndrome is considered when there is hemimegalencephaly, extensive lymphangitic or vascular malformations and asymmetric hemi-hypertrophy 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

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

• Klippel-Trénaunay syndrome
• neurofibromatosis type 1
• epidermal naevus syndrome
• encephalocraniocutaneous lipomatosis
• CLOVE syndrome
• Maffucci syndrome/Ollier disease

History and etymology

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/hemi-hypertrophy 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.