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Rothmund–Thomson syndrome

January 01, 1970

Rothmund–Thomson syndrome (RTS) is a rare autosomal recessive[3][4] skin condition.

Rothmund–Thomson syndrome
Other namesPoikiloderma atrophicans with cataract or Poikiloderma congenitale[1][2]
Panel showing some clinical features of the RTS syndrome. A) Chronic phase of cheek poikiloderma (4-year-old girl). B) Poikiloderma with alopecia (21-year-old boy). C) Poikiloderma. D) Poikiloderma sparing the trunk (courtesy of Professor M. Paradisi, Rome). E) Photo distributed poikiloderma and valgism of the knees. F) Thumb aplasia (patient B). G) Bone defect seen by X-Rays: cystic-like destructive lesion of the humerus (distal epiphysis) without apparent solution of continuity of the cortical bone (patient E).
SpecialtyMedical genetics 

There have been several reported cases associated with osteosarcoma. A hereditary basis, mutations in the DNA helicase RECQL4 gene, causing problems during initiation of DNA replication has been implicated in the syndrome.[1][5][6][7]

Signs and symptoms edit

  • Sun-sensitive rash with prominent poikiloderma and telangiectasias
  • Juvenile cataracts
  • Saddle nose
  • Congenital bone defects, including short stature and radial ray anomalies such as absent thumbs
  • Hair growth problems (absent eyelashes, eyebrows and/or hair)
  • Hypogonadism has not been well documented
  • Hypodontia
  • Calcium problems (not documented in journals)
  • Ear problems (not documented in journals but identified by patients in support groups)
  • Produces osteosarcoma[8]

The skin is normal at birth. Between 3 and 6 months of age, the affected carrier develops poikiloderma on the cheeks. This characteristic "rash" that all RTS carriers have can develop on the arms, legs and buttocks. "Poikiloderma consists of areas of increased and decreased pigmentation, prominent blood vessels, and thinning of the skin."[9]

Accelerated aging edit

In humans, individuals with RTS, and carrying the RECQL4 germline mutation, can have several clinical features of accelerated aging. These features include atrophic skin and pigment changes, alopecia, osteopenia, cataracts and an increased incidence of cancer.[10] Also in mice, RECQL4 mutants show features of accelerated aging.[11]

Causes edit

 
Rothmund–Thomson syndrome has an autosomal recessive pattern of inheritance.

RTS is caused by a mutation of the RECQL4 gene, located at chromosome 8q24.3.[5][12] The disorder is inherited in an autosomal recessive manner.[3] This means the defective gene responsible for the disorder is located on an autosome (chromosome 8 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.[citation needed]

DNA repair edit

RECQL4 has a crucial role in DNA end resection that is the initial step required for homologous recombination (HR)-dependent double-strand break repair.[13] When RECQL4 is depleted, HR-mediated repair and 5’ end resection are severely reduced in vivo. RECQL4 also appears to be necessary for other forms of DNA repair including non-homologous end joining, nucleotide excision repair and base excision repair.[10] The association of deficient RECQL4-mediated DNA repair with accelerated aging is consistent with the DNA damage theory of aging.[citation needed]

Diagnosis edit

Management edit

History edit

The condition was originally described by August von Rothmund (1830–1906) in 1868.[14] Matthew Sydney Thomson (1894–1969) published further descriptions in 1936.[15]

See also edit

References edit

  1. ^ a b Online Mendelian Inheritance in Man (OMIM): 268400
  2. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. p. 576. ISBN 978-0-7216-2921-6.
  3. ^ a b Larizza, L.; Roversi, G.; Volpi, L. (Jan 2010). "Rothmund-Thomson syndrome". Orphanet Journal of Rare Diseases (Free full text). 5: 2. doi:10.1186/1750-1172-5-2. PMC 2826297. PMID 20113479.
  4. ^ Raza N, Malik QU, Hussain Z (2007). "Rothmund-Thomson syndrome: more than just a cosmetic concern". J Coll Physicians Surg Pak. 17 (7): 423–424. PMID 17686357.
  5. ^ a b Larizza L, Magnani I, Roversi G (January 2006). "Rothmund–Thomson syndrome and RECQL4 defect: Splitting and lumping". Cancer Letters. 232 (1): 107–120. doi:10.1016/j.canlet.2005.07.042. PMID 16271439.
  6. ^ Hicks MJ, Roth JR, Kozinetz CA, Wang LL (2007). "Clinicopathologic features of osteosarcoma in patients with Rothmund-Thomson syndrome". J. Clin. Oncol. 25 (4): 370–5. doi:10.1200/JCO.2006.08.4558. PMID 17264332.
  7. ^ Sangrithi MN, Bernal JA, Madine M, Philpott A, Lee J, Dunphy WG, Venkitaraman AR (Jun 2005). "Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund-Thomson syndrome". Cell. 121 (6): 887–98. doi:10.1016/j.cell.2005.05.015. PMID 15960976. S2CID 15064074.
  8. ^ Wang LL, Levy ML, Lewis RA, et al. (2001). "Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients". Am. J. Med. Genet. 102 (1): 11–17. doi:10.1002/1096-8628(20010722)102:1<11::AID-AJMG1413>3.0.CO;2-A. PMID 11471165.
  9. ^ Understanding RTS pamphlet, RTS Team: Lisa L. Wang (Oncologist), Moise L. Levy (dermatologist), Richard A. Lewis (Ophthalmologist), Sharon E. Plon (Geneticist)
  10. ^ a b Lu L, Jin W, Wang LL (2017). "Aging in Rothmund-Thomson syndrome and related RECQL4 genetic disorders". Ageing Res. Rev. 33: 30–35. doi:10.1016/j.arr.2016.06.002. PMID 27287744. S2CID 28321025.
  11. ^ Lu H, Fang EF, Sykora P, Kulikowicz T, Zhang Y, Becker KG, Croteau DL, Bohr VA (2014). "Senescence induced by RECQL4 dysfunction contributes to Rothmund-Thomson syndrome features in mice". Cell Death Dis. 5 (5): e1226. doi:10.1038/cddis.2014.168. PMC 4047874. PMID 24832598.
  12. ^ Online Mendelian Inheritance in Man (OMIM): 603780
  13. ^ Lu H, Shamanna RA, Keijzers G, Anand R, Rasmussen LJ, Cejka P, Croteau DL, Bohr VA (2016). "RECQL4 Promotes DNA End Resection in Repair of DNA Double-Strand Breaks". Cell Rep. 16 (1): 161–73. doi:10.1016/j.celrep.2016.05.079. PMC 5576896. PMID 27320928.
  14. ^ Lu, Linchao; Jin, Weidong; Wang, Lisa L. (2016). "Aging in Rothmund-Thomson syndrome and related RECQL4 genetic disorders". Ageing Research Reviews. 33: 30–35. doi:10.1016/j.arr.2016.06.002. ISSN 1568-1637. PMID 27287744. S2CID 28321025.
  15. ^ Thomson, MS. (Mar 1936). "Poikiloderma Congenitale: Two Cases for Diagnosis". Proc R Soc Med. 29 (5): 453–5. PMC 2076117. PMID 19990626.

External links edit

  • GeneReviews/NCBI/NIH/UW entry on Rothmund-Thomson Syndrome
  • Poikiloderma of Rothmund-Thomson at NIH's Office of Rare Diseases

January 01, 1970
rothmund, thomson, syndrome, rare, autosomal, recessive, skin, condition, other, namespoikiloderma, atrophicans, with, cataract, poikiloderma, congenitale, panel, showing, some, clinical, features, syndrome, chronic, phase, cheek, poikiloderma, year, girl, poi. Rothmund Thomson syndrome RTS is a rare autosomal recessive 3 4 skin condition Rothmund Thomson syndromeOther namesPoikiloderma atrophicans with cataract or Poikiloderma congenitale 1 2 Panel showing some clinical features of the RTS syndrome A Chronic phase of cheek poikiloderma 4 year old girl B Poikiloderma with alopecia 21 year old boy C Poikiloderma D Poikiloderma sparing the trunk courtesy of Professor M Paradisi Rome E Photo distributed poikiloderma and valgism of the knees F Thumb aplasia patient B G Bone defect seen by X Rays cystic like destructive lesion of the humerus distal epiphysis without apparent solution of continuity of the cortical bone patient E SpecialtyMedical genetics There have been several reported cases associated with osteosarcoma A hereditary basis mutations in the DNA helicase RECQL4 gene causing problems during initiation of DNA replication has been implicated in the syndrome 1 5 6 7 Contents 1 Signs and symptoms 1 1 Accelerated aging 2 Causes 2 1 DNA repair 3 Diagnosis 4 Management 5 History 6 See also 7 References 8 External linksSigns and symptoms editSun sensitive rash with prominent poikiloderma and telangiectasias Juvenile cataracts Saddle nose Congenital bone defects including short stature and radial ray anomalies such as absent thumbs Hair growth problems absent eyelashes eyebrows and or hair Hypogonadism has not been well documented Hypodontia Calcium problems not documented in journals Ear problems not documented in journals but identified by patients in support groups Produces osteosarcoma 8 The skin is normal at birth Between 3 and 6 months of age the affected carrier develops poikiloderma on the cheeks This characteristic rash that all RTS carriers have can develop on the arms legs and buttocks Poikiloderma consists of areas of increased and decreased pigmentation prominent blood vessels and thinning of the skin 9 Accelerated aging edit In humans individuals with RTS and carrying the RECQL4 germline mutation can have several clinical features of accelerated aging These features include atrophic skin and pigment changes alopecia osteopenia cataracts and an increased incidence of cancer 10 Also in mice RECQL4 mutants show features of accelerated aging 11 Causes edit nbsp Rothmund Thomson syndrome has an autosomal recessive pattern of inheritance RTS is caused by a mutation of the RECQL4 gene located at chromosome 8q24 3 5 12 The disorder is inherited in an autosomal recessive manner 3 This means the defective gene responsible for the disorder is located on an autosome chromosome 8 is an autosome and two copies of the defective gene one inherited from each parent are required in order to be born with the disorder The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene but usually do not experience any signs or symptoms of the disorder citation needed DNA repair edit RECQL4 has a crucial role in DNA end resection that is the initial step required for homologous recombination HR dependent double strand break repair 13 When RECQL4 is depleted HR mediated repair and 5 end resection are severely reduced in vivo RECQL4 also appears to be necessary for other forms of DNA repair including non homologous end joining nucleotide excision repair and base excision repair 10 The association of deficient RECQL4 mediated DNA repair with accelerated aging is consistent with the DNA damage theory of aging citation needed Diagnosis editThis section is empty You can help by adding to it August 2017 Management editThis section is empty You can help by adding to it August 2017 History editThe condition was originally described by August von Rothmund 1830 1906 in 1868 14 Matthew Sydney Thomson 1894 1969 published further descriptions in 1936 15 See also editPoikiloderma vasculare atrophicans List of cutaneous conditions List of radiographic findings associated with cutaneous conditionsReferences edit a b Online Mendelian Inheritance in Man OMIM 268400 James William Berger Timothy Elston Dirk 2005 Andrews Diseases of the Skin Clinical Dermatology 10th ed Saunders p 576 ISBN 978 0 7216 2921 6 a b Larizza L Roversi G Volpi L Jan 2010 Rothmund Thomson syndrome Orphanet Journal of Rare Diseases Free full text 5 2 doi 10 1186 1750 1172 5 2 PMC 2826297 PMID 20113479 Raza N Malik QU Hussain Z 2007 Rothmund Thomson syndrome more than just a cosmetic concern J Coll Physicians Surg Pak 17 7 423 424 PMID 17686357 a b Larizza L Magnani I Roversi G January 2006 Rothmund Thomson syndrome and RECQL4 defect Splitting and lumping Cancer Letters 232 1 107 120 doi 10 1016 j canlet 2005 07 042 PMID 16271439 Hicks MJ Roth JR Kozinetz CA Wang LL 2007 Clinicopathologic features of osteosarcoma in patients with Rothmund Thomson syndrome J Clin Oncol 25 4 370 5 doi 10 1200 JCO 2006 08 4558 PMID 17264332 Sangrithi MN Bernal JA Madine M Philpott A Lee J Dunphy WG Venkitaraman AR Jun 2005 Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund Thomson syndrome Cell 121 6 887 98 doi 10 1016 j cell 2005 05 015 PMID 15960976 S2CID 15064074 Wang LL Levy ML Lewis RA et al 2001 Clinical manifestations in a cohort of 41 Rothmund Thomson syndrome patients Am J Med Genet 102 1 11 17 doi 10 1002 1096 8628 20010722 102 1 lt 11 AID AJMG1413 gt 3 0 CO 2 A PMID 11471165 Understanding RTS pamphlet RTS Team Lisa L Wang Oncologist Moise L Levy dermatologist Richard A Lewis Ophthalmologist Sharon E Plon Geneticist a b Lu L Jin W Wang LL 2017 Aging in Rothmund Thomson syndrome and related RECQL4 genetic disorders Ageing Res Rev 33 30 35 doi 10 1016 j arr 2016 06 002 PMID 27287744 S2CID 28321025 Lu H Fang EF Sykora P Kulikowicz T Zhang Y Becker KG Croteau DL Bohr VA 2014 Senescence induced by RECQL4 dysfunction contributes to Rothmund Thomson syndrome features in mice Cell Death Dis 5 5 e1226 doi 10 1038 cddis 2014 168 PMC 4047874 PMID 24832598 Online Mendelian Inheritance in Man OMIM 603780 Lu H Shamanna RA Keijzers G Anand R Rasmussen LJ Cejka P Croteau DL Bohr VA 2016 RECQL4 Promotes DNA End Resection in Repair of DNA Double Strand Breaks Cell Rep 16 1 161 73 doi 10 1016 j celrep 2016 05 079 PMC 5576896 PMID 27320928 Lu Linchao Jin Weidong Wang Lisa L 2016 Aging in Rothmund Thomson syndrome and related RECQL4 genetic disorders Ageing Research Reviews 33 30 35 doi 10 1016 j arr 2016 06 002 ISSN 1568 1637 PMID 27287744 S2CID 28321025 Thomson MS Mar 1936 Poikiloderma Congenitale Two Cases for Diagnosis Proc R Soc Med 29 5 453 5 PMC 2076117 PMID 19990626 External links editGeneReviews NCBI NIH UW entry on Rothmund Thomson Syndrome Poikiloderma of Rothmund Thomson at NIH s Office of Rare Diseases Retrieved from https en wikipedia org w index php title Rothmund Thomson syndrome amp oldid 1223214309, wikipedia, wiki, book, books, library,

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