Proteus syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]

Synonyms and keywords:PS

Overview

Proteus syndrome is an exceedingly rare disorder which falls under the category of hamartomatous disorder. Proteus syndrome is a very complex disorder which involves multiple organ systems in the body.

Historical Perspective

Discovery

Proteus syndrome was first discovered by Frederick Treves, a British surgeon, in 1884.
Frederick Treves showed the proteus syndrome on Joseph Merrick, who used to be called as the famous Elephant Man, to the Pathological Society of London.

Classification

Proteus syndrome is one of the syndromes which falls under PTEN hamartoma tumor syndromes (PHTS). PHTS are due to germline mutations in PTEN gene.
PTEN hamartoma tumor syndromes (PHTS) which include the following:
- Proteus syndrome
- Cowden syndrome
- Bannayan-Riley-Ruvalcaba syndrome
- Lhermitte-Duclos disease
- Autism spectrum disorders
- https://selly.gg/@brandon122

Pathophysiology

Genes involved in the pathogenesis of proteus syndrome include: Mutations in the AKT1 and PTEN gene leads to oncogenesis
Phosphatase and tensin homolog (PTEN) gene plays an important role in the following:^[1]^[2]^[3]^[4]
- Phosphoinositide-3-kinase (PI3K)-AKT pathway and
- Rapamycin (mTOR) signaling pathways
PTEN track backs to 10q23 which encodes and plays a significant role in the following:^[5]^[6]^[7]
- Effects G1 cell cycle arrest and apoptosis
- Cellular proliferation and
- Migration
- Apoptosis

Causes

The most common cause of proteus syndrome is a mutation which has mosaic variant in a gene called AKT1 and phosphatase and tensin homolog (PTEN) mutations in some patients.^[8]

Differentiating Proteus syndrome from other Diseases

Epidemiology and Demographics

Incidence

The incidence of proteus syndrome is approximately 1 per 1,000,000 individuals worldwide.

Race

There is no racial predilection to proteus syndrome.

Gender

Males are more commonly affected by proteus syndrome than females.

Risk Factors

Screening

Natural History, Complications, and Prognosis

Diagnosis

Diagnostic study of choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-Ray Findings

Echocardiography and Ultrasound

CT-Scan Findings

MRI Findings

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

References

↑ Caux F, Plauchu H, Chibon F, Faivre L, Fain O, Vabres P, Bonnet F, Selma ZB, Laroche L, Gérard M, Longy M (July 2007). "Segmental overgrowth, lipomatosis, arteriovenous malformation and epidermal nevus (SOLAMEN) syndrome is related to mosaic PTEN nullizygosity". Eur. J. Hum. Genet. 15 (7): 767–73. doi:10.1038/sj.ejhg.5201823. PMID 17392703.
↑ Zhou X, Hampel H, Thiele H, Gorlin RJ, Hennekam RC, Parisi M, Winter RM, Eng C (July 2001). "Association of germline mutation in the PTEN tumour suppressor gene and Proteus and Proteus-like syndromes". Lancet. 358 (9277): 210–1. PMID 11476841.
↑ Happle R (2007). "Linear Cowden nevus: a new distinct epidermal nevus". Eur J Dermatol. 17 (2): 133–6. doi:10.1684/ejd.2007.0125. PMID 17337396.
↑ Nelen MR, Padberg GW, Peeters EA, Lin AY, van den Helm B, Frants RR, Coulon V, Goldstein AM, van Reen MM, Easton DF, Eeles RA, Hodgsen S, Mulvihill JJ, Murday VA, Tucker MA, Mariman EC, Starink TM, Ponder BA, Ropers HH, Kremer H, Longy M, Eng C (May 1996). "Localization of the gene for Cowden disease to chromosome 10q22-23". Nat. Genet. 13 (1): 114–6. doi:10.1038/ng0596-114. PMID 8673088.
↑ Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, Ruland J, Penninger JM, Siderovski DP, Mak TW (October 1998). "Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN". Cell. 95 (1): 29–39. PMID 9778245.
↑ Nelen MR, Padberg GW, Peeters EA, Lin AY, van den Helm B, Frants RR, Coulon V, Goldstein AM, van Reen MM, Easton DF, Eeles RA, Hodgsen S, Mulvihill JJ, Murday VA, Tucker MA, Mariman EC, Starink TM, Ponder BA, Ropers HH, Kremer H, Longy M, Eng C (May 1996). "Localization of the gene for Cowden disease to chromosome 10q22-23". Nat. Genet. 13 (1): 114–6. doi:10.1038/ng0596-114. PMID 8673088.
↑ Keniry M, Parsons R (September 2008). "The role of PTEN signaling perturbations in cancer and in targeted therapy". Oncogene. 27 (41): 5477–85. doi:10.1038/onc.2008.248. PMID 18794882.
↑ Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM, Peters K, Turner J, Cannons JL, Bick D, Blakemore L, Blumhorst C, Brockmann K, Calder P, Cherman N, Deardorff MA, Everman DB, Golas G, Greenstein RM, Kato BM, Keppler-Noreuil KM, Kuznetsov SA, Miyamoto RT, Newman K, Ng D, O'Brien K, Rothenberg S, Schwartzentruber DJ, Singhal V, Tirabosco R, Upton J, Wientroub S, Zackai EH, Hoag K, Whitewood-Neal T, Robey PG, Schwartzberg PL, Darling TN, Tosi LL, Mullikin JC, Biesecker LG (August 2011). "A mosaic activating mutation in AKT1 associated with the Proteus syndrome". N. Engl. J. Med. 365 (7): 611–9. doi:10.1056/NEJMoa1104017. PMC 3170413. PMID 21793738.

[pmid17392703-1] Caux F, Plauchu H, Chibon F, Faivre L, Fain O, Vabres P, Bonnet F, Selma ZB, Laroche L, Gérard M, Longy M (July 2007). "Segmental overgrowth, lipomatosis, arteriovenous malformation and epidermal nevus (SOLAMEN) syndrome is related to mosaic PTEN nullizygosity". Eur. J. Hum. Genet. 15 (7): 767–73. doi:10.1038/sj.ejhg.5201823. PMID 17392703.

[pmid11476841-2] Zhou X, Hampel H, Thiele H, Gorlin RJ, Hennekam RC, Parisi M, Winter RM, Eng C (July 2001). "Association of germline mutation in the PTEN tumour suppressor gene and Proteus and Proteus-like syndromes". Lancet. 358 (9277): 210–1. PMID 11476841.

[pmid17337396-3] Happle R (2007). "Linear Cowden nevus: a new distinct epidermal nevus". Eur J Dermatol. 17 (2): 133–6. doi:10.1684/ejd.2007.0125. PMID 17337396.

[pmid86730883-4] Nelen MR, Padberg GW, Peeters EA, Lin AY, van den Helm B, Frants RR, Coulon V, Goldstein AM, van Reen MM, Easton DF, Eeles RA, Hodgsen S, Mulvihill JJ, Murday VA, Tucker MA, Mariman EC, Starink TM, Ponder BA, Ropers HH, Kremer H, Longy M, Eng C (May 1996). "Localization of the gene for Cowden disease to chromosome 10q22-23". Nat. Genet. 13 (1): 114–6. doi:10.1038/ng0596-114. PMID 8673088.

[pmid9778245-5] Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, Ruland J, Penninger JM, Siderovski DP, Mak TW (October 1998). "Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN". Cell. 95 (1): 29–39. PMID 9778245.

[pmid8673088-6] Nelen MR, Padberg GW, Peeters EA, Lin AY, van den Helm B, Frants RR, Coulon V, Goldstein AM, van Reen MM, Easton DF, Eeles RA, Hodgsen S, Mulvihill JJ, Murday VA, Tucker MA, Mariman EC, Starink TM, Ponder BA, Ropers HH, Kremer H, Longy M, Eng C (May 1996). "Localization of the gene for Cowden disease to chromosome 10q22-23". Nat. Genet. 13 (1): 114–6. doi:10.1038/ng0596-114. PMID 8673088.

[pmid18794882-7] Keniry M, Parsons R (September 2008). "The role of PTEN signaling perturbations in cancer and in targeted therapy". Oncogene. 27 (41): 5477–85. doi:10.1038/onc.2008.248. PMID 18794882.

[pmid21793738-8] Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM, Peters K, Turner J, Cannons JL, Bick D, Blakemore L, Blumhorst C, Brockmann K, Calder P, Cherman N, Deardorff MA, Everman DB, Golas G, Greenstein RM, Kato BM, Keppler-Noreuil KM, Kuznetsov SA, Miyamoto RT, Newman K, Ng D, O'Brien K, Rothenberg S, Schwartzentruber DJ, Singhal V, Tirabosco R, Upton J, Wientroub S, Zackai EH, Hoag K, Whitewood-Neal T, Robey PG, Schwartzberg PL, Darling TN, Tosi LL, Mullikin JC, Biesecker LG (August 2011). "A mosaic activating mutation in AKT1 associated with the Proteus syndrome". N. Engl. J. Med. 365 (7): 611–9. doi:10.1056/NEJMoa1104017. PMC 3170413. PMID 21793738.

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