Proteus syndrome

2008-04-01   Peter L Choyke , Leslie G Biesecker 

Molecular Imaging Program, Building 10, Room 1B40, 9000 Rockville Pike, Bethesda, MD 20892-1088, USA (PLC); National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive Room 4A56, Bethesda, MD 20892-4472, USA (LGB)



Proteus syndrome


Elattoproteus syndrome , Gigantism , Encephalocraniocutaneous lipomatosis , Elephant man syndrome


Proteus is a sporadic disorder resulting in a mosaic pattern of tissue overgrowth. The most common manifestations are macrodactyly, asymmetric fat and \/or muscle and bone distribution, connective tissue and epidermal nevi, lymphatic and vascular malformations, and hyperostoses.








744 Proteus syndrome




Phenotype and clinics

General criteria for the diagnosis include mosaic distribution of lesions, progressive course from birth, sporadic occurrence. Supportive findings include connective tissue nevi (characteristically on the soles of the feet and\/or on the chest wall), epidermal nevus, disproportionate overgrowth leading to asymmetry. Asymmetric dysregulation of fat in the subcutaneous space lead to unilateral or localized overgrowth and contralateral atrophy of subcutaneous fat. The spine commonly demonstrates scoliosis. Bullous lung disease is often seen and can lead to respiratory insufficiency and pneumonias. Benign tumors include lipomas, lymphangiomas, epidermal nevi, and vascular malformations. There is an increased risk of pulmonary embolism and this is a prominent cause of early death. Cord compression can result from fatty overgrowth into the spinal canal.

Neoplastic risk

The risk of malignancy is low. Benign tumors include lipomas, hemangiomas, vascular malformations, lymphangiomas. Neoplasms that have been reported include a mesothelioma, papillary carcinoma of the thyroid, ovarian serous cystadenoma, meningioma, optic nerve tumor and endometrial carcinoma but no systematic risk for particular tumors has been observed.


Treatment is usually conservative and symptomatic. Surgical repair of severe skeletal distortion is performed although growth is often progressive despite procedures. There is growing concern over the risk of pulmonary embolism although clinical recommendations for prevention have not been established.


Longevity is likely affected by Proteus syndrome. A known cause of premature death is pulmonary embolism. Respiratory deaths due to cystic lung disease, massive rib overgrowth and laryngospasm have also been reported. CNS deaths have also occurred from seizures and a cerebellar abscess.



No cytogenetic aberrations have been observed in patients with confirmed Proteus syndrome.

Genes involved and Proteins


The gene responsible for Proteus syndrome are unknown. This gene, however, is overexpressed in Proteus-associated tumors such as lipomas, salivary gland tumors, leiomyomas and lung hamartomas.


The evidence implicating this gene in Proteus syndrome is weak.


Pubmed IDLast YearTitleAuthors
168833082006The challenges of Proteus syndrome: diagnosis and management.Biesecker L et al
164627302005Misdiagnosis of neurofibromatosis type 1 as Proteus syndrome.Biesecker LG et al
145180702003Proteus syndrome: misdiagnosis with PTEN mutations.Cohen MM Jr et al
160106812005Proteus syndrome: an update.Cohen MM Jr et al
155992242004Vascular anomalies and the growth of limbs: a review.Enjolras O et al
169449822006Unusual fallopian tube neoplasm in a 10-year-old patient with Proteus syndrome: a case report and review of the literature.Funk T et al
151154982004Vascular anomalies in Proteus syndrome.Hoeger PH et al
182058552008Histopathological features of Proteus syndrome.Hoey SE et al
152566282004Radiologic manifestations of Proteus syndrome.Jamis-Dow CA et al
120777612002Principles for the surgical management of patients with Proteus syndrome and patients with overgrowth not meeting Proteus criteria.Lublin M et al
163516612005Proteus syndrome with giant myelolipoma in the pelvis.Matsumoto S et al
119102282002Proteus syndrome in adulthood.Müller E et al
164216722006Perioperative respiratory complications caused by cystic lung malformation in Proteus syndrome.Nakane M et al
153138102004Cutaneous manifestations of proteus syndrome: correlations with general clinical severity.Nguyen D et al
177020222007Parenting children with Proteus syndrome: experiences with, and adaptation to, courtesy stigma.Turner J et al
153725142004Reassessment of the Proteus syndrome literature: application of diagnostic criteria to published cases.Turner JT et al
158584742005Evolution of skin lesions in Proteus syndrome.Twede JV et al
162380852005Paraparesis caused by an angiolipomatous hamartoma in an adolescent with Proteus syndrome and scoliosis.White NJ et al

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