Proteus syndrome

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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. In The United States of America in order to categorise a condition is a rare disease it should affect fewer than 200,000 people. Rare diseases also called as orphan diseases. Orphan Drug Act was passed on 1983 by congress for the rare diseases. Today an average of 25-30 million americans have been reported with rare diseases. The number of people with individual rare disease may be less but overall the number of people with rare diseases are large in number.

Historical Perspective

Discovery

  • Proteus syndrome was first discovered by Frederick Treves, a British surgeon, in 1884.[1]
  • 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.[2][3]

Classification

Pathophysiology

Causes

Differentiating Proteus syndrome from other Diseases

Proteus syndrome must be differentiated from the following rare disorders:[18][19][20][21][22][23]

Epidemiology and Demographics

Incidence

  • The incidence of proteus syndrome is approximately 1 per 1,000,000-1:10,000,000 individuals worldwide.[24][25]
  • There are few than 100 cases of proteus syndrome have been reported worldwide.

Race

  • There is no racial predilection to proteus syndrome.[26]

Gender

  • Males are more commonly affected by proteus syndrome than females.

Risk Factors

Screening

  • There is insufficient evidence to recommend routine screening for proteus syndrome.

Natural History, Complications, and Prognosis

Natural History

Complications

Prognosis

  • Prognosis is generally excellent in mildly affected children with proteus syndrome.[35]
  • Depending on the location of the gene and the degree of the overgrowth at the time of diagnosis, the prognosis may vary.[36]
  • Survival rate of patients with proteus syndrome is approximately ranges from nine months to 29 years based on the severity of the condition.[37]

Diagnosis

Diagnostic study of choice

Diagnostic criteria of Proteus syndrome includes the following:

  • According to the National Institutes of Health in 1998, diagnosis of the proteus syndrome requires the following:[42]
    • Positive all general characteristics and one feature of category A or two features of category of B or three features of category C
General criteria

(All are Required)[43][44]

Specific criteria

Category A[45][46]

Specific criteria

Category B[47][48]

Specific criteria

Category C[49][50]

(All the three are reuired)

  • Asymmetric or disproportionate overgrowth

of one or more of the following:

limbs, digits, cranium, vertebrae, spleen

external auditory meatus, and or thymus

  • Specific tumors with onset before the second decade:

Bilateral ovarian cystadenomas or parotid monomorphic adenoma

  • Following a progressive course

History and Symptoms

History

Common Symptoms[54][55]

Physical Examination

Skin

Back

HEENT

Extremities

Proteus syndrome overgrowth
Proteus syndrome- Note the generalized overgrowth, upper and lower limb length discrepancy, localized limb distortion of the left knee (A), postural flexion deformity of the left knee (B), and mild dorsal scoliotic deformity (C). Case courtesy by Tamer Ahmed EL-Sobky Et Al[63]
X-ray in Proteus Syndrome- Asymmetric and disproportionate overgrowth of right hand fingers with macrodactyly. Case courtesy -Suresh Kumar Angurana Et Al[64]
Proteus syndrome
(A) Right hemihypertrophy, (B) subcutaneous tumors and lipoma, (C) macrodactyly of the third and fourth digits of the right hand, and (D) macrodactyly of nearly all the toes. Pic courtesy by Zuleyha Sik Sarman Et Al [68]

Laboratory Findings

Electrocardiogram

  • There are no ECG findings associated with proteus syndrome.

X-Ray Findings

Ultrasound

CT-Scan Findings

MRI Findings

Temporal lobe cavernoma
Magnetic resonance imaging of the case, showing temporal lobe cavernoma, Pic courtesy by Zuleyha Sik Sarman Et Al [83]

Treatment

Medical Therapy

  • The majority of cases of proteus syndrome require orthopedic management and it is challenging.

Surgery

  • Surgery is the mainstay of treatment for proteus syndrome patients.

Epiphysiostasis and Epiphysiodesis

  • Epiphysiostasis is a form of surgery which helps in reduces projected limb length which is a form of temporary growth arrest.[84][85][86]
  • Epiphysiostasis is done in children with proteus syndrome who are many years away from puberty.
  • Epiphysiostasis is only considered and done in overgrowth limb not the normal limb which is short.
  • Epiphysiodesis is usally considered when the patient enters into teens.
  • The advantage of doing epiphysiostasis and epiphysiodesis the patients can be ambulatory after the surgery very fast and it reduces the risk of formation of thrombosis.[87]

Amputation

Patellectomy

Spinal Bracing

  • Spinal bracing considered in patients with scoliosis in proteus syndrome due to life-threatening consequences.[90]
  • Spinal bracing should be considered when the patients with proteus syndrome when spinal curve as small as 10°.

Joint Replacement

Foot Care

Primary Prevention

Secondary Prevention

References

  1. Lindhurst, Marjorie J.; Sapp, Julie C.; Teer, Jamie K.; Johnston, Jennifer J.; Finn, Erin M.; Peters, Kathryn; Turner, Joyce; Cannons, Jennifer L.; Bick, David; Blakemore, Laurel; Blumhorst, Catherine; Brockmann, Knut; Calder, Peter; Cherman, Natasha; Deardorff, Matthew A.; Everman, David B.; Golas, Gretchen; Greenstein, Robert M.; Kato, B. Maya; Keppler-Noreuil, Kim M.; Kuznetsov, Sergei A.; Miyamoto, Richard T.; Newman, Kurt; Ng, David; O'Brien, Kevin; Rothenberg, Steven; Schwartzentruber, Douglas J.; Singhal, Virender; Tirabosco, Roberto; Upton, Joseph; Wientroub, Shlomo; Zackai, Elaine H.; Hoag, Kimberly; Whitewood-Neal, Tracey; Robey, Pamela G.; Schwartzberg, Pamela L.; Darling, Thomas N.; Tosi, Laura L.; Mullikin, James C.; Biesecker, Leslie G. (2011). "A Mosaic Activating Mutation inAKT1Associated with the Proteus Syndrome". New England Journal of Medicine. 365 (7): 611–619. doi:10.1056/NEJMoa1104017. ISSN 0028-4793.
  2. Hashemieh M, Mansoori B, Tavakoli R, Sheibani K (June 2012). "A case of concurrent proteus syndrome and hemophilia a". Iran J Pediatr. 22 (2): 255–9. PMC 3446058. PMID 23056896.
  3. De Souza, RAG (2012). "Origins of the elephant man: mosaic somatic mutations cause Proteus syndrome". Clinical Genetics. 81 (2): 123–124. doi:10.1111/j.1399-0004.2011.01807.x. ISSN 0009-9163.
  4. Marsh DJ, Kum JB, Lunetta KL, Bennett MJ, Gorlin RJ, Ahmed SF, Bodurtha J, Crowe C, Curtis MA, Dasouki M, Dunn T, Feit H, Geraghty MT, Graham JM, Hodgson SV, Hunter A, Korf BR, Manchester D, Miesfeldt S, Murday VA, Nathanson KL, Parisi M, Pober B, Romano C, Eng C (August 1999). "PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome". Hum. Mol. Genet. 8 (8): 1461–72. PMID 10400993.
  5. Lachlan KL, Lucassen AM, Bunyan D, Temple IK (September 2007). "Cowden syndrome and Bannayan Riley Ruvalcaba syndrome represent one condition with variable expression and age-related penetrance: results of a clinical study of PTEN mutation carriers". J. Med. Genet. 44 (9): 579–85. doi:10.1136/jmg.2007.049981. PMC 2597943. PMID 17526800.
  6. Marsh DJ, Coulon V, Lunetta KL, Rocca-Serra P, Dahia PL, Zheng Z, Liaw D, Caron S, Duboué B, Lin AY, Richardson AL, Bonnetblanc JM, Bressieux JM, Cabarrot-Moreau A, Chompret A, Demange L, Eeles RA, Yahanda AM, Fearon ER, Fricker JP, Gorlin RJ, Hodgson SV, Huson S, Lacombe D, Eng C (March 1998). "Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation". Hum. Mol. Genet. 7 (3): 507–15. PMID 9467011.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. Krymskaya VP, Goncharova EA (February 2009). "PI3K/mTORC1 activation in hamartoma syndromes: therapeutic prospects". Cell Cycle. 8 (3): 403–13. doi:10.4161/cc.8.3.7555. PMID 19177005.
  12. Sansal I, Sellers WR (July 2004). "The biology and clinical relevance of the PTEN tumor suppressor pathway". J. Clin. Oncol. 22 (14): 2954–63. doi:10.1200/JCO.2004.02.141. PMID 15254063.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. De Souza, RAG (2012). "Origins of the elephant man: mosaic somatic mutations cause Proteus syndrome". Clinical Genetics. 81 (2): 123–124. doi:10.1111/j.1399-0004.2011.01807.x. ISSN 0009-9163.
  18. Alomari AI (January 2009). "Characterization of a distinct syndrome that associates complex truncal overgrowth, vascular, and acral anomalies: a descriptive study of 18 cases of CLOVES syndrome". Clin. Dysmorphol. 18 (1): 1–7. doi:10.1097/MCD.0b013e328317a716. PMID 19011570.
  19. Sapp JC, Turner JT, van de Kamp JM, van Dijk FS, Lowry RB, Biesecker LG (December 2007). "Newly delineated syndrome of congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome) in seven patients". Am. J. Med. Genet. A. 143A (24): 2944–58. doi:10.1002/ajmg.a.32023. PMID 17963221.
  20. Acosta S, Torres V, Paulos M, Cifuentes I (April 2017). "CLOVES Syndrome: Severe Neonatal Presentation". J Clin Diagn Res. 11 (4): TR01–TR03. doi:10.7860/JCDR/2017/23801.9719. PMC 5449880. PMID 28571234.
  21. Michel ME, Konczyk DJ, Yeung KS, Murillo R, Vivero MP, Hall AM, Zurakowski D, Adams D, Gupta A, Huang AY, Chung B, Warman ML (May 2018). "Causal somatic mutations in urine DNA from persons with the CLOVES subgroup of the PIK3CA-related overgrowth spectrum". Clin. Genet. 93 (5): 1075–1080. doi:10.1111/cge.13195. PMID 29231959. Vancouver style error: initials (help)
  22. Marsh DJ, Kum JB, Lunetta KL, Bennett MJ, Gorlin RJ, Ahmed SF, Bodurtha J, Crowe C, Curtis MA, Dasouki M, Dunn T, Feit H, Geraghty MT, Graham JM, Hodgson SV, Hunter A, Korf BR, Manchester D, Miesfeldt S, Murday VA, Nathanson KL, Parisi M, Pober B, Romano C, Eng C (August 1999). "PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome". Hum. Mol. Genet. 8 (8): 1461–72. PMID 10400993.
  23. Lachlan KL, Lucassen AM, Bunyan D, Temple IK (September 2007). "Cowden syndrome and Bannayan Riley Ruvalcaba syndrome represent one condition with variable expression and age-related penetrance: results of a clinical study of PTEN mutation carriers". J. Med. Genet. 44 (9): 579–85. doi:10.1136/jmg.2007.049981. PMC 2597943. PMID 17526800.
  24. Lindhurst, Marjorie J.; Sapp, Julie C.; Teer, Jamie K.; Johnston, Jennifer J.; Finn, Erin M.; Peters, Kathryn; Turner, Joyce; Cannons, Jennifer L.; Bick, David; Blakemore, Laurel; Blumhorst, Catherine; Brockmann, Knut; Calder, Peter; Cherman, Natasha; Deardorff, Matthew A.; Everman, David B.; Golas, Gretchen; Greenstein, Robert M.; Kato, B. Maya; Keppler-Noreuil, Kim M.; Kuznetsov, Sergei A.; Miyamoto, Richard T.; Newman, Kurt; Ng, David; O'Brien, Kevin; Rothenberg, Steven; Schwartzentruber, Douglas J.; Singhal, Virender; Tirabosco, Roberto; Upton, Joseph; Wientroub, Shlomo; Zackai, Elaine H.; Hoag, Kimberly; Whitewood-Neal, Tracey; Robey, Pamela G.; Schwartzberg, Pamela L.; Darling, Thomas N.; Tosi, Laura L.; Mullikin, James C.; Biesecker, Leslie G. (2011). "A Mosaic Activating Mutation inAKT1Associated with the Proteus Syndrome". New England Journal of Medicine. 365 (7): 611–619. doi:10.1056/NEJMoa1104017. ISSN 0028-4793.
  25. Rocha R, Estrella M, Amaral D, Barbosa AM, Abreu M (2017). "Proteus syndrome". An Bras Dermatol. 92 (5): 717–720. doi:10.1590/abd1806-4841.20174496. PMID 29166516. Vancouver style error: initials (help)
  26. Lindhurst, Marjorie J.; Sapp, Julie C.; Teer, Jamie K.; Johnston, Jennifer J.; Finn, Erin M.; Peters, Kathryn; Turner, Joyce; Cannons, Jennifer L.; Bick, David; Blakemore, Laurel; Blumhorst, Catherine; Brockmann, Knut; Calder, Peter; Cherman, Natasha; Deardorff, Matthew A.; Everman, David B.; Golas, Gretchen; Greenstein, Robert M.; Kato, B. Maya; Keppler-Noreuil, Kim M.; Kuznetsov, Sergei A.; Miyamoto, Richard T.; Newman, Kurt; Ng, David; O'Brien, Kevin; Rothenberg, Steven; Schwartzentruber, Douglas J.; Singhal, Virender; Tirabosco, Roberto; Upton, Joseph; Wientroub, Shlomo; Zackai, Elaine H.; Hoag, Kimberly; Whitewood-Neal, Tracey; Robey, Pamela G.; Schwartzberg, Pamela L.; Darling, Thomas N.; Tosi, Laura L.; Mullikin, James C.; Biesecker, Leslie G. (2011). "A Mosaic Activating Mutation inAKT1Associated with the Proteus Syndrome". New England Journal of Medicine. 365 (7): 611–619. doi:10.1056/NEJMoa1104017. ISSN 0028-4793.
  27. Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean L, Stephens K, Amemiya A, Biesecker LG, Sapp JC. PMID 22876373. Vancouver style error: initials (help); Missing or empty |title= (help)
  28. Rocha, Ritha de Cássia Capelato; Estrella, Mariani Paulino Soriano; Amaral, Danielle Mechereffe do; Barbosa, Angela Marques; Abreu, Marilda Aparecida Milanez Morgado de (2017). "Proteus syndrome". Anais Brasileiros de Dermatologia. 92 (5): 717–720. doi:10.1590/abd1806-4841.20174496. ISSN 0365-0596.
  29. Rocha R, Estrella M, Amaral D, Barbosa AM, Abreu M (2017). "Proteus syndrome". An Bras Dermatol. 92 (5): 717–720. doi:10.1590/abd1806-4841.20174496. PMC 5674710. PMID 29166516. Vancouver style error: initials (help)
  30. Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean L, Stephens K, Amemiya A, Biesecker LG, Sapp JC. PMID 22876373. Vancouver style error: initials (help); Missing or empty |title= (help)
  31. Biesecker L (November 2006). "The challenges of Proteus syndrome: diagnosis and management". Eur. J. Hum. Genet. 14 (11): 1151–7. doi:10.1038/sj.ejhg.5201638. PMID 16883308.
  32. Poduri A, Evrony GD, Cai X, Elhosary PC, Beroukhim R, Lehtinen MK, Hills LB, Heinzen EL, Hill A, Hill RS, Barry BJ, Bourgeois BF, Riviello JJ, Barkovich AJ, Black PM, Ligon KL, Walsh CA (April 2012). "Somatic activation of AKT3 causes hemispheric developmental brain malformations". Neuron. 74 (1): 41–8. doi:10.1016/j.neuron.2012.03.010. PMID 22500628.
  33. Alcantara D, Timms AE, Gripp K, Baker L, Park K, Collins S, Cheng C, Stewart F, Mehta SG, Saggar A, Sztriha L, Zombor M, Caluseriu O, Mesterman R, Van Allen MI, Jacquinet A, Ygberg S, Bernstein JA, Wenger AM, Guturu H, Bejerano G, Gomez-Ospina N, Lehman A, Alfei E, Pantaleoni C, Conti V, Guerrini R, Moog U, Graham JM, Hevner R, Dobyns WB, O'Driscoll M, Mirzaa GM (October 2017). "Mutations of AKT3 are associated with a wide spectrum of developmental disorders including extreme megalencephaly". Brain. 140 (10): 2610–2622. doi:10.1093/brain/awx203. PMC 6080423. PMID 28969385.
  34. Lopes F, Torres F, Soares G, van Karnebeek CD, Martins C, Antunes D, Silva J, Muttucomaroe L, Botelho LF, Sousa S, Rendeiro P, Tavares P, Van Esch H, Rajcan-Separovic E, Maciel P (2019). "The Role of AKT3 Copy Number Changes in Brain Abnormalities and Neurodevelopmental Disorders: Four New Cases and Literature Review". Front Genet. 10: 58. doi:10.3389/fgene.2019.00058. PMC 6395382. PMID 30853971.
  35. Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean L, Stephens K, Amemiya A, Biesecker LG, Sapp JC. PMID 22876373. Vancouver style error: initials (help); Missing or empty |title= (help)
  36. Rocha, Ritha de Cássia Capelato; Estrella, Mariani Paulino Soriano; Amaral, Danielle Mechereffe do; Barbosa, Angela Marques; Abreu, Marilda Aparecida Milanez Morgado de (2017). "Proteus syndrome". Anais Brasileiros de Dermatologia. 92 (5): 717–720. doi:10.1590/abd1806-4841.20174496. ISSN 0365-0596.
  37. Rocha R, Estrella M, Amaral D, Barbosa AM, Abreu M (2017). "Proteus syndrome". An Bras Dermatol. 92 (5): 717–720. doi:10.1590/abd1806-4841.20174496. PMC 5674710. PMID 29166516. Vancouver style error: initials (help)
  38. Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean L, Stephens K, Amemiya A, Biesecker LG, Sapp JC. PMID 22876373. Vancouver style error: initials (help); Missing or empty |title= (help)
  39. De Souza, RAG (2012). "Origins of the elephant man: mosaic somatic mutations cause Proteus syndrome". Clinical Genetics. 81 (2): 123–124. doi:10.1111/j.1399-0004.2011.01807.x. ISSN 0009-9163.
  40. Smeets E, Fryns JP, Cohen MM (May 1994). "Regional Proteus syndrome and somatic mosaicism". Am. J. Med. Genet. 51 (1): 29–31. doi:10.1002/ajmg.1320510107. PMID 8030665.
  41. Erickson RP (March 2003). "Somatic gene mutation and human disease other than cancer". Mutat. Res. 543 (2): 125–36. PMID 12644182.
  42. Biesecker LG, Happle R, Mulliken JB, Weksberg R, Graham JM, Viljoen DL, Cohen MM (June 1999). "Proteus syndrome: diagnostic criteria, differential diagnosis, and patient evaluation". Am. J. Med. Genet. 84 (5): 389–95. PMID 10360391.
  43. Rocha, Ritha de Cássia Capelato; Estrella, Mariani Paulino Soriano; Amaral, Danielle Mechereffe do; Barbosa, Angela Marques; Abreu, Marilda Aparecida Milanez Morgado de (2017). "Proteus syndrome". Anais Brasileiros de Dermatologia. 92 (5): 717–720. doi:10.1590/abd1806-4841.20174496. ISSN 0365-0596.
  44. Turner JT, Cohen MM, Biesecker LG (October 2004). "Reassessment of the Proteus syndrome literature: application of diagnostic criteria to published cases". Am. J. Med. Genet. A. 130A (2): 111–22. doi:10.1002/ajmg.a.30327. PMID 15372514.
  45. Thomason JL, Abramowsky CR, Rickets RR, Culbertson JH, Clifton MS, Shehata BM (June 2012). "Proteus syndrome: three case reports with a review of the literature". Fetal Pediatr Pathol. 31 (3): 145–53. doi:10.3109/15513815.2012.656830. PMID 22413928.
  46. Beachkofsky TM, Sapp JC, Biesecker LG, Darling TN (November 2010). "Progressive overgrowth of the cerebriform connective tissue nevus in patients with Proteus syndrome". J. Am. Acad. Dermatol. 63 (5): 799–804. doi:10.1016/j.jaad.2009.12.012. PMC 3240941. PMID 20709429.
  47. Rocha, Ritha de Cássia Capelato; Estrella, Mariani Paulino Soriano; Amaral, Danielle Mechereffe do; Barbosa, Angela Marques; Abreu, Marilda Aparecida Milanez Morgado de (2017). "Proteus syndrome". Anais Brasileiros de Dermatologia. 92 (5): 717–720. doi:10.1590/abd1806-4841.20174496. ISSN 0365-0596.
  48. Turner JT, Cohen MM, Biesecker LG (October 2004). "Reassessment of the Proteus syndrome literature: application of diagnostic criteria to published cases". Am. J. Med. Genet. A. 130A (2): 111–22. doi:10.1002/ajmg.a.30327. PMID 15372514.
  49. Rocha, Ritha de Cássia Capelato; Estrella, Mariani Paulino Soriano; Amaral, Danielle Mechereffe do; Barbosa, Angela Marques; Abreu, Marilda Aparecida Milanez Morgado de (2017). "Proteus syndrome". Anais Brasileiros de Dermatologia. 92 (5): 717–720. doi:10.1590/abd1806-4841.20174496. ISSN 0365-0596.
  50. Turner JT, Cohen MM, Biesecker LG (October 2004). "Reassessment of the Proteus syndrome literature: application of diagnostic criteria to published cases". Am. J. Med. Genet. A. 130A (2): 111–22. doi:10.1002/ajmg.a.30327. PMID 15372514.
  51. Newman B, Urbach AH, Orenstein D, Dickman PS (1994). "Proteus syndrome: emphasis on the pulmonary manifestations". Pediatr Radiol. 24 (3): 189–93. PMID 7936796.
  52. Launois C, Vallerand H, Perotin JM, Nardi J, Dury S, Toubas O, Lebargy F, Deslée G (November 2013). "[The Proteus syndrome: a rare cause of pulmonary emphysema]". Rev Mal Respir (in French). 30 (9): 789–93. doi:10.1016/j.rmr.2013.04.020. PMID 24267771.
  53. Lim GY, Kim OH, Kim HW, Lee KS, Kang KH, Song HR, Cho TJ (April 2011). "Pulmonary manifestations in Proteus syndrome: pulmonary varicosities and bullous lung disease". Am. J. Med. Genet. A. 155A (4): 865–9. doi:10.1002/ajmg.a.33926. PMID 21412980.
  54. Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean L, Stephens K, Amemiya A, Biesecker LG, Sapp JC. PMID 22876373. Vancouver style error: initials (help); Missing or empty |title= (help)
  55. Tosi LL, Sapp JC, Allen ES, O'Keefe RJ, Biesecker LG (October 2011). "Assessment and management of the orthopedic and other complications of Proteus syndrome". J Child Orthop. 5 (5): 319–27. doi:10.1007/s11832-011-0350-6. PMC 3179535. PMID 23024722.
  56. Sarman ZS, Yuksel N, Sarman H, Bayramgurler D (June 2014). "Proteus syndrome: report of a case with developmental glaucoma". Korean J Ophthalmol. 28 (3): 272–4. doi:10.3341/kjo.2014.28.3.272. PMC 4038735. PMID 24882963.
  57. Rocha R, Estrella M, Amaral D, Barbosa AM, Abreu M (2017). "Proteus syndrome". An Bras Dermatol. 92 (5): 717–720. doi:10.1590/abd1806-4841.20174496. PMC 5674710. PMID 29166516. Vancouver style error: initials (help)
  58. Biesecker L (November 2006). "The challenges of Proteus syndrome: diagnosis and management". Eur. J. Hum. Genet. 14 (11): 1151–7. doi:10.1038/sj.ejhg.5201638. PMID 16883308.
  59. Mayatepek E, Kurczynski TW, Ruppert ES, Hennessy JR, Brinker RA, French BN (March 1989). "Expanding the phenotype of the Proteus syndrome: a severely affected patient with new findings". Am. J. Med. Genet. 32 (3): 402–6. doi:10.1002/ajmg.1320320327. PMID 2729359.
  60. Rocha R, Estrella M, Amaral D, Barbosa AM, Abreu M (2017). "Proteus syndrome". An Bras Dermatol. 92 (5): 717–720. doi:10.1590/abd1806-4841.20174496. PMC 5674710. PMID 29166516. Vancouver style error: initials (help)
  61. Rocha R, Estrella M, Amaral D, Barbosa AM, Abreu M (2017). "Proteus syndrome". An Bras Dermatol. 92 (5): 717–720. doi:10.1590/abd1806-4841.20174496. PMC 5674710. PMID 29166516. Vancouver style error: initials (help)
  62. Biesecker L (November 2006). "The challenges of Proteus syndrome: diagnosis and management". Eur. J. Hum. Genet. 14 (11): 1151–7. doi:10.1038/sj.ejhg.5201638. PMID 16883308.
  63. "Orthopaedic manifestations of Proteus syndrome in a child with literature update".
  64. "Proteus syndrome: Clinical profile of six patients and review of literature".
  65. Biesecker L (November 2006). "The challenges of Proteus syndrome: diagnosis and management". Eur. J. Hum. Genet. 14 (11): 1151–7. doi:10.1038/sj.ejhg.5201638. PMID 16883308.
  66. Rocha R, Estrella M, Amaral D, Barbosa AM, Abreu M (2017). "Proteus syndrome". An Bras Dermatol. 92 (5): 717–720. doi:10.1590/abd1806-4841.20174496. PMC 5674710. PMID 29166516. Vancouver style error: initials (help)
  67. Viljoen DL, Nelson MM, de Jong G, Beighton P (May 1987). "Proteus syndrome in southern Africa: natural history and clinical manifestations in six individuals". Am. J. Med. Genet. 27 (1): 87–97. doi:10.1002/ajmg.1320270110. PMID 3605209.
  68. "Proteus Syndrome: Report of a Case with Developmental Glaucoma".
  69. Tosi, Laura L.; Sapp, Julie C.; Allen, Elizabeth S.; O’Keefe, Regis J.; Biesecker, Leslie G. (2011). "Assessment and management of the orthopedic and other complications of Proteus syndrome". Journal of Children's Orthopaedics. 5 (5): 319–327. doi:10.1007/s11832-011-0350-6. ISSN 1863-2521.
  70. Kaduthodil MJ, Prasad DS, Lowe AS, Punekar AS, Yeung S, Kay CL (September 2012). "Imaging manifestations in Proteus syndrome: an unusual multisystem developmental disorder". Br J Radiol. 85 (1017): e793–9. doi:10.1259/bjr/92343528. PMC 3487101. PMID 22514103.
  71. Angurana SK, Angurana RS, Panigrahi I, Marwaha RK (April 2013). "Proteus syndrome: Clinical profile of six patients and review of literature". Indian J Hum Genet. 19 (2): 202–6. doi:10.4103/0971-6866.116117. PMC 3758728. PMID 24019623.
  72. Tosi, Laura L.; Sapp, Julie C.; Allen, Elizabeth S.; O’Keefe, Regis J.; Biesecker, Leslie G. (2011). "Assessment and management of the orthopedic and other complications of Proteus syndrome". Journal of Children's Orthopaedics. 5 (5): 319–327. doi:10.1007/s11832-011-0350-6. ISSN 1863-2521.
  73. Popescu MD, Burnei G, Draghici L, Draghici I (2014). "Proteus Syndrome: a difficult diagnosis and management plan". J Med Life. 7 (4): 563–6. PMC 4316140. PMID 25713623.
  74. Cohen MM (August 2005). "Proteus syndrome: an update". Am J Med Genet C Semin Med Genet. 137C (1): 38–52. doi:10.1002/ajmg.c.30063. PMID 16010681.
  75. Jamis-Dow CA, Turner J, Biesecker LG, Choyke PL (2004). "Radiologic manifestations of Proteus syndrome". Radiographics. 24 (4): 1051–68. doi:10.1148/rg.244035726. PMID 15256628.
  76. "Radiographic findings of Proteus Syndrome".
  77. Tosi LL, Sapp JC, Allen ES, O'Keefe RJ, Biesecker LG (October 2011). "Assessment and management of the orthopedic and other complications of Proteus syndrome". J Child Orthop. 5 (5): 319–27. doi:10.1007/s11832-011-0350-6. PMC 3179535. PMID 23024722.
  78. Vanhoenacker FM, De Beuckeleer LH, Deprettere A, De Moor A, De Schepper AM (February 2000). "Proteus syndrome: MRI characteristics of plantar cerebriform hyperplasia". Skeletal Radiol. 29 (2): 101–3. PMID 10741500.
  79. Beachkofsky TM, Sapp JC, Biesecker LG, Darling TN (November 2010). "Progressive overgrowth of the cerebriform connective tissue nevus in patients with Proteus syndrome". J. Am. Acad. Dermatol. 63 (5): 799–804. doi:10.1016/j.jaad.2009.12.012. PMC 3240941. PMID 20709429.
  80. Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean L, Stephens K, Amemiya A, Biesecker LG, Sapp JC. PMID 22876373. Vancouver style error: initials (help); Missing or empty |title= (help)
  81. Sarman ZS, Yuksel N, Sarman H, Bayramgurler D (June 2014). "Proteus syndrome: report of a case with developmental glaucoma". Korean J Ophthalmol. 28 (3): 272–4. doi:10.3341/kjo.2014.28.3.272. PMC 4038735. PMID 24882963.
  82. Burke JP, Bowell R, O'Doherty N (1988). "Proteus syndrome: ocular complications". J Pediatr Ophthalmol Strabismus. 25 (2): 99–102. PMID 3282059.
  83. "Proteus Syndrome: Report of a Case with Developmental Glaucoma".
  84. Tosi LL, Sapp JC, Allen ES, O'Keefe RJ, Biesecker LG (October 2011). "Assessment and management of the orthopedic and other complications of Proteus syndrome". J Child Orthop. 5 (5): 319–27. doi:10.1007/s11832-011-0350-6. PMC 3179535. PMID 23024722.
  85. Popescu MD, Burnei G, Draghici L, Draghici I (2014). "Proteus Syndrome: a difficult diagnosis and management plan". J Med Life. 7 (4): 563–6. PMC 4316140. PMID 25713623.
  86. Pinkowski JL, Weiner DS (1995). "Complications in proximal tibial osteotomies in children with presentation of technique". J Pediatr Orthop. 15 (3): 307–12. PMID 7790485.
  87. Crenshaw, Molly M.; Goerlich, Cara G.; Ivey, Lauren E.; Sapp, Julie C.; Keppler-Noreuil, Kim M.; Scott, Allison C.; Biesecker, Leslie G.; Tosi, Laura L. (2018). "Orthopaedic Management of Leg-length Discrepancy in Proteus Syndrome". Journal of Pediatric Orthopaedics. 38 (3): e138–e144. doi:10.1097/BPO.0000000000001121. ISSN 0271-6798.
  88. Raboudi, T.; Bouchoucha, S.; Hamdi, B.; Boussetta, R.; Saied, W.; Jalel, C.; Smida, M. (2014). "Soft-tissue necrosis complicating tibial osteotomy in a child with Proteus syndrome". Orthopaedics & Traumatology: Surgery & Research. 100 (2): 251–254. doi:10.1016/j.otsr.2013.10.016. ISSN 1877-0568.
  89. Guidera KJ, Brinker MR, Kousseff BG, Helal AA, Pugh LI, Ganey TM, Ogden JA (1993). "Overgrowth management in Klippel-Trenaunay-Weber and Proteus syndromes". J Pediatr Orthop. 13 (4): 459–66. PMID 8396594.
  90. Stricker S (1992). "Musculoskeletal manifestations of Proteus syndrome: report of two cases with literature review". J Pediatr Orthop. 12 (5): 667–74. PMID 1517432.
  91. Raboudi, T.; Bouchoucha, S.; Hamdi, B.; Boussetta, R.; Saied, W.; Jalel, C.; Smida, M. (2014). "Soft-tissue necrosis complicating tibial osteotomy in a child with Proteus syndrome". Orthopaedics & Traumatology: Surgery & Research. 100 (2): 251–254. doi:10.1016/j.otsr.2013.10.016. ISSN 1877-0568.
  92. Beachkofsky TM, Sapp JC, Biesecker LG, Darling TN (November 2010). "Progressive overgrowth of the cerebriform connective tissue nevus in patients with Proteus syndrome". J. Am. Acad. Dermatol. 63 (5): 799–804. doi:10.1016/j.jaad.2009.12.012. PMC 3240941. PMID 20709429.
  93. Nathan NR, Patel R, Crenshaw MM, Lindhurst MJ, Olsen C, Biesecker LG, Keppler-Noreuil KM, Darling TN (April 2018). "Pathogenetic insights from quantification of the cerebriform connective tissue nevus in Proteus syndrome". J. Am. Acad. Dermatol. 78 (4): 725–732. doi:10.1016/j.jaad.2017.10.018. PMC 5857242. PMID 29042227.
  94. Thomason JL, Abramowsky CR, Rickets RR, Culbertson JH, Clifton MS, Shehata BM (June 2012). "Proteus syndrome: three case reports with a review of the literature". Fetal Pediatr Pathol. 31 (3): 145–53. doi:10.3109/15513815.2012.656830. PMID 22413928.
  95. Beachkofsky, Thomas M.; Sapp, Julie C.; Biesecker, Leslie G.; Darling, Thomas N. (2010). "Progressive overgrowth of the cerebriform connective tissue nevus in patients with Proteus syndrome". Journal of the American Academy of Dermatology. 63 (5): 799–804. doi:10.1016/j.jaad.2009.12.012. ISSN 0190-9622.
  96. Angurana SK, Angurana RS (May 2014). "Proteus syndrome: More vigilance needed to diagnose it". Indian J Endocrinol Metab. 18 (3): 429–30. doi:10.4103/2230-8210.131225. PMC 4056150. PMID 24944946.
  97. Wenz, Wolfram; Berrsche, Gregor (2014). "Proteus Syndrome". Techniques in Foot & Ankle Surgery. 13 (4): 206–211. doi:10.1097/BTF.0000000000000062. ISSN 1536-0644.