The Proteus Syndrome is a rare condition with a highly variable clinical expression. Patients may show a combination of connective tissue nevi, epidermal nevi, overgrowth of various tissues, vascular malformations or benign tumors. These criteria were defined by the First National Conference on Proteus Syndrome held at NIH in 1998.

Mandatory general criteria:

(1) mosaic distribution of lesions

(2) progressive course, with some tendency of tissue overgrowth to plateau after adolescence

(3) sporadic occurrence


Genetics postulates:

(1) The condition is caused by somatic mosaicism, with the nonmosaic state lethal.

(2) The trait is neither simply mendelian nor entirely nonmendelian and sometimes imitates a dominant transmission (= "paradominance").


Lesion Category




connective tissue nevus



epidermal nevus



disproportionate overgrowth

affecting limbs OR skull OR external auditory meatus OR vertebrae OR viscera


specific tumors occurring before end of second decade

bilateral ovarian cystadenomas OR parotid monomorphic adenoma


dysregulated adipose tissue

lipoma OR regional absence of fat


vascular malformations

capillary malformations OR venous malformation OR lymphatic malformation


facial phenotype

combination of: dolichocephaly, long face, minor downslanting of palpebral fissures and/or mild ptosis, low nasal bridge, wide or anteverted nares, open mouth at rest



• overgrowth of limbs may affect the arms, legs, hands, feet and/or digits

• overgrowth of skull = hyperostosis

• overgrowth of external auditory meatus = hyperostosis

• overgrowth of vertebrae = megaspondylodysplasia

• overgrowth of viscera may affect spleen or thymus

• dolichocephaly = long headed (cephalic index <= 75.9, see Chapter 2)


Diagnostic criteria:

(1) all 3 mandatory general criteria

(2) one or more of the following:

(2a) 1 out of 1 item from category A

(2b) 2 out of 3 items from category B

(2c) 3 out of 3 items from category C


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