Proteus Syndrome

from Wikipedia, the free encyclopedia
Classification according to ICD-10
Q89.0 Other specified congenital malformations
ICD-10 online (WHO version 2019)

The Proteus syndrome is a congenital disorder that manifests itself in early childhood, a regional overgrowth. Tumors often develop .

Proteus syndrome has a diverse clinical appearance. That is why it was named by the German pediatrician Hans-Rudolf Wiedemann after the Greek god of the sea, Proteus , who is said to have been able to change his external shape.

Since the first description of the syndrome by Michael Cohen in 1979, about 200 cases have been described worldwide. However, today's diagnostic criteria are only met in just under half of these cases. Since milder forms of the disease can also occur, it can be assumed that some cases of Proteus syndrome will not be diagnosed as such.

Notable cases

Joseph Merrick, photographed for a study in 1889

Joseph Merrick suffered from Proteus syndrome, presumably combined with neurofibromatosis type 1 (Recklinghausen's disease) and became known as the elephant man .

Only his left arm and genitals were unaffected.

Clinical appearance

Proteus syndrome causes skin, bones, muscles, adipose tissue, blood and lymph vessels to grow large. At birth, those affected are usually without any obvious changes.

With increasing age, the described large growth and tumor formation can occur. The severity and location of the infestation varies extremely, but the skull, one or more extremities, and the soles of the feet are often affected. Life expectancy is reduced in those affected by the increased occurrence of deep vein thromboses and pulmonary embolisms, which are favored by disease-associated vascular malformations. The increased weight of the deformed extremities also leads to muscle and joint pain. Further risks can arise from the mass of tissue overgrowths - as in the case of Joseph Merrick, who suffocated in his sleep when his cervical spine collapsed under the weight of his head.

The illness itself does not cause intellectual retardation or learning disabilities. The tall stature can cause secondary damage to the nervous system, which leads to cognitive impairment. In addition, visible deformations have a negative impact on the patient's social experience, which can lead to cognitive and social deficits.

Those affected are at increased risk of developing certain tumors such as unilateral ovarian cystadenomas, testicular tumors, meningiomas and adenomas of the salivary gland.

Causes - Genetics

Research into the exact cause of Proteus syndrome is ongoing. Some research shows a link to the PTEN gene on chromosome 10 , while other results suggest chromosome 16 . Some scientists have expressed doubts about the involvement of PTEN.

A somatic mutation as a cause is also the subject of scientific discussion.

In 2011, a study found a point mutation in the AKT1 gene in 26 of 29 patients examined. The mutation leads to a genetic mosaic that leads to overgrowth of the affected body parts.

treatment

There is currently no treatment. An Australian team of doctors examined sirolimus as a possible therapeutic agent in a case report and found a positive effect on the progression of the disease.

See also

supporting documents

  1. ^ LG Biesecker, R. Happle, JB Mulliken, R. Weksberg, JM Graham Jr, DL Viljoen, MM Cohen Jr .: Proteus syndrome: diagnostic criteria, differential diagnosis, and patient evaluation. In: Am J Med Genet. tape 84 (5) , 1999, pp. 389-395 , PMID 10360391 .
  2. ↑ Freedberg et al: Fitzpatrick's Dermatology in General Medicine. 6th edition. McGraw-Hill, 2003, ISBN 0-07-138076-0 .
  3. ↑ C. Jamis-Dow, J. Turner, L. Biesecker, P. Choyke: Radiologic manifestations of Proteus syndrome . In: Radiographics . tape 24 , no. 4 , 2004, p. 1051-1068 , doi : 10.1148 / rg.244035726 , PMID 15256628 .
  4. ^ HR Wiedemann, GR Burgio, P. Aldenhoff, J. Kunze, HJ Kaufmann, E. Schirg: The proteus syndrome. Partial gigantism of the hands and / or feet, nevi, hemihypertrophy, subcutaneous tumors, macrocephaly or other skull anomalies and possible accelerated growth and visceral affections. In: Eur J Pediatr. tape 140 (1) , 1983, pp. 5-12 , PMID 6873112 .
  5. ↑ MM Cohen, PW Hayden: A newly recognized hamartomatous syndrome . In: Birth Defects Orig. Artic. Ser. tape 15 , 5B, 1979, pp. 291-296 , PMID 118782 .
  6. ↑ JT Turner, MM Cohen Jr., LG Biesecker: Reassessment of the Proteus syndrome literature: application of diagnostic criteria to published cases. In: Am J Med Genet A . 130A (2), 2004, pp. 111-122 , PMID 15372514 .
  7. ^ J. Tibbles, M. Cohen: The Proteus syndrome: the Elephant Man diagnosed . In: Br Med J (Clin Res Ed) . tape 293 , no. 6548 , 1986, pp. 683-685 , PMID 3092979 .
  8. ^ P. Spiring: The Improbable Elephant Man. In: Biologist. (London) 48 (3), p. 104 .; - The Sunday Telegraph , - BBC News , - Eurekalert !, - The Daily Telegraph
  9. ↑ JM Smith, EP Kirk, G. Theodosopoulos et al .: Germline mutation of the tumor suppressor PTEN in Proteus syndrome . In: J. Med. Genet. tape 39 , no. 12 , 2002, p. 937-940 , doi : 10.1136 / jmg.39.12.937 , PMID 12471211 .
  10. ^ MT Cardoso, TB de Carvalho, LA Casulari, I. Ferrari: Proteus syndrome and somatic mosaicism of the chromosome 16 . In: Panminerva medica . tape 45 , no. 4 , 2003, p. 267-271 , PMID 15206168 .
  11. ^ I. Thiffault, CE Schwartz, V. Der Kaloustian, WD Foulkes: Mutation analysis of the tumor suppressor PTEN and the glypican 3 (GPC3) gene in patients diagnosed with Proteus syndrome . In: Am. J. Med. Genet. A . 130A, no. 2 , October 2004, p. 123-127 , doi : 10.1002 / ajmg.a.30335 , PMID 15372512 .
  12. ↑ K. Brockmann, R. Happle, F. Oeffner, A. König: Monozygotic twins discordant for Proteus syndrome . In: Am. J. Med. Genet. A . 146A, no. 16 , August 2008, p. 2122-2125 , doi : 10.1002 / ajmg.a.32417 , PMID 18627057 .
  13. ↑ Marjorie J. Lindhurst, Julie C. Sapp, Jamie K. Teer, Jennifer J. Johnston, Erin M. Finn, Kathryn Peters, Joyce Turner, Jennifer L. Cannons, David Bick, Laurel Blakemore, Catherine Blumhorst, Knut Brockmann, Peter Calder, Natasha Cherman, Matthew A. Deardorff, David B. Everman, Gretchen Golas, Robert M. Greenstein, B. Maya Kato, Kim M. Keppler-Noreuil, Sergei A. Kuznetsov, Richard T. Miyamoto, Kurt Newman, David Ng , Kevin O'Brien, Steven Rothenberg, Douglas J. Schwartzentruber, Virender Singhal, Roberto Tirabosco, Joseph Upton, Shlomo Wientroub, Elaine H. Zackai, Kimberly Hoag, Tracey Whitewood-Neal, Pamela G. Robey, Pamela L. Schwartzberg, Thomas N. Darling, Laura L. Tosi, James C. Mullikin, Leslie G. Biesecker: A Mosaic Activating Mutation in AKT1 Associated with the Proteus Syndrome . In: New England Journal of Medicine . tape 0 , no. 0 , July 2011, doi : 10.1056 / NEJMoa1104017 .
  14. ^ Catalyst: Noah's Hope. abc.net.au, August 14, 2008, accessed May 29, 2013 .
  15. ↑ DJ Marsh et al.: Rapamycin treatment for a child with germline PTEN mutation. In: Nat Clin Pract Oncol . 2008 Jun; 5 (6), pp. 357-361. PMID 18431376 .

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