Rothmund-Thomson Syndrome Clinical Presentation

  • Author: Sylvia Hsu, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Jul 11, 2011
 

History

Patients with Rothmund-Thomson syndrome (poikiloderma congenitale) generally present with a rash (poikiloderma), small stature, and skeletal dysplasias.

  • The characteristic skin findings are the most consistent feature of the syndrome.
    • The acute phase begins in early infancy as red patches or edematous plaques, sometimes with blistering. The cheeks are usually first involved, with later spread to other areas of the face, the extremities, and the buttocks.
    • Over months to years, the rash enters a chronic stage characterized by poikiloderma (atrophy, telangiectasias, and pigmentary changes).
  • Photosensitivity is a feature in more than 30% of cases.
  • Gastrointestinal problems such as chronic emesis or diarrhea may occur in infancy and early childhood but usually resolve spontaneously. Celiac disease has been reported.[6]
  • Hematological abnormalities ranging from isolated anemia and neutropenia to myelodysplasia and leukemia have also been noted to occur.
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Physical

  • In Rothmund-Thomson syndrome (poikiloderma congenitale), irregular erythema and edema of the skin is replaced by reticulated red-brown patches associated with punctate atrophy and telangiectasias (poikiloderma). These characteristic skin changes are typically seen on the face, extensor extremities, and buttocks with sparing of the chest, abdomen, and back. See the images below. Note the poikiloderma and skeletal abnormalities. Note the poikiloderma and skeletal abnormalities. Close-up of poikiloderma. Close-up of poikiloderma. Close-up of poikiloderma. Close-up of poikiloderma.
  • Acral hyperkeratotic lesions on the elbows, knees, hands, and feet can be seen at puberty. Palmar keratoderma has been reported.[6]
  • Patients may have sparse scalp hair, eyelashes, and eyebrows. Premature canities may also be observed.
  • Nail abnormalities such as dystrophic or atrophic nails may be seen.
  • Dental abnormalities include malformation, microdontia, and failure of eruption.
  • Juvenile cataracts have been reported to occur with a prevalence that has been estimated at less than 10% in some series and as high as 40-50% in others. Most develop between age 3 and 7 years.
  • Patients usually have short stature, which ranges from dwarfism to a small build. More than half of patients have skeletal abnormalities, most frequently a characteristic facies (with frontal bossing, saddle nose, and micrognathia), disproportionately small hands and feet, absent or malformed radii, and absent or partially formed thumbs.
  • Sexual abnormalities, affecting about 25% of adult patients, include hypoplasia and/or aplasia of the external genitalia, amenorrhea, lack of secondary sex characteristics, and infertility.
  • Otsu et al report a patient who had some uncommon complications of Rothmund-Thomson syndrome (poikiloderma congenitale) and many typical features, but the patient did not have a mutation in RECQL4; therefore, they suggest this case was a "peculiar" variant of Rothmund-Thomson syndrome.[7]
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Causes

Rothmund-Thomson syndrome (poikiloderma congenitale) has been attributed to mutations of the RECQL4 gene on 8q24, which encodes a RecQ DNA helicase.[1, 2, 3, 8] RecQ helicases are enzymes that function in DNA replication and repair and appear to be essential for the maintenance of genomic stability.[9, 10] Reports on the characteristics of the RECQL4 helicase gene include those by Dietschy et al,[11] Maire et al,[12] and Wu et al.[13] . A strong correlation appears to exist between the presence of truncating, loss-of-function mutations of the RECQL4 gene and the development of skeletal abnormalities and osteosarcoma.

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Contributor Information and Disclosures
Author

Sylvia Hsu, MD  Professor, Department of Dermatology, Baylor College of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Saira J George, MD  Staff Dermatologist, Dermatological Association of Texas

Saira J George, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Bernice R Krafchik, MBChB, FRCPC  Professor Emeritus, Department of Pediatrics, Section of Dermatology, University of Toronto

Bernice R Krafchik, MBChB, FRCPC is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, Canadian Medical Association, College of Physicians and Surgeons of Ontario, Royal College of Physicians and Surgeons of Canada, and Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

Michael J Wells, MD  Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Van Perry, MD  Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery

Disclosure: Nothing to disclose.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

References

  1. Kitao S, Shimamoto A, Goto M, et al. Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome. Nat Genet. May 1999;22(1):82-4. [Medline].

  2. Kitao S, Lindor NM, Shiratori M, Furuichi Y, Shimamoto A. Rothmund-thomson syndrome responsible gene, RECQL4: genomic structure and products. Genomics. Nov 1 1999;61(3):268-76. [Medline].

  3. Larizza L, Magnani I, Roversi G. Rothmund-Thomson syndrome and RECQL4 defect: splitting and lumping. Cancer Lett. Jan 28 2006;232(1):107-20. [Medline].

  4. Leonard A, Craft AW, Moss C, Malcolm AJ. Osteogenic sarcoma in the Rothmund-Thomson syndrome. Med Pediatr Oncol. Apr 1996;26(4):249-53. [Medline].

  5. Wang LL, Gannavarapu A, Kozinetz CA, et al. Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. J Natl Cancer Inst. May 7 2003;95(9):669-74. [Medline].

  6. Popadic S, Nikolic M, Gajic-Veljic M, Bonaci-Nikolic B. Rothmund-Thomson syndrome. The first case with plantar keratoderma and the second with coeliac disease. Acta Dermatovenerol Alp Panonica Adriat. Jun 2006;15(2):90-3. [Medline].

  7. Otsu U, Moriwaki S, Iki M, Nozaki K, Horiguchi Y, Kiyokane K. Early blistering, poikiloderma, hypohidrosis, alopecia and exocrine pancreatic hypofunction: a peculiar variant of Rothmund-Thomson syndrome?. Eur J Dermatol. Nov-Dec 2008;18(6):632-4. [Medline].

  8. Macris MA, Krejci L, Bussen W, Shimamoto A, Sung P. Biochemical characterization of the RECQ4 protein, mutated in Rothmund-Thomson syndrome. DNA Repair (Amst). Feb 3 2006;5(2):172-80. [Medline].

  9. Werner SR, Prahalad AK, Yang J, Hock JM. RECQL4-deficient cells are hypersensitive to oxidative stress/damage: Insights for osteosarcoma prevalence and heterogeneity in Rothmund-Thomson syndrome. Biochem Biophys Res Commun. Jun 23 2006;345(1):403-9. [Medline].

  10. Woo LL, Futami K, Shimamoto A, Furuichi Y, Frank KM. The Rothmund-Thomson gene product RECQL4 localizes to the nucleolus in response to oxidative stress. Exp Cell Res. Oct 15 2006;312(17):3443-57. [Medline].

  11. Dietschy T, Shevelev I, Pena-Diaz J, et al. p300-mediated acetylation of the Rothmund-Thomson-syndrome gene product RECQL4 regulates its subcellular localization. J Cell Sci. Apr 15 2009;122:1258-67. [Medline].

  12. Maire G, Yoshimoto M, Chilton-MacNeill S, Thorner PS, Zielenska M, Squire JA. Recurrent RECQL4 imbalance and increased gene expression levels are associated with structural chromosomal instability in sporadic osteosarcoma. Neoplasia. Mar 2009;11(3):260-8, 3p following 268. [Medline].

  13. Wu J, Capp C, Feng L, Hsieh TS. Drosophila homologue of the Rothmund-Thomson syndrome gene: essential function in DNA replication during development. Dev Biol. Nov 1 2008;323(1):130-42. [Medline].

  14. Prendiville JS, Fine JD, Esterly NB. Kindler syndrome and epidermolysis bullosa simplex. J Am Acad Dermatol. Aug 1990;23(2 Pt 1):327-8. [Medline].

  15. Geronemus RG. Treatment of the cutaneous vascular component of the Rothmund-Thomson syndrome. Pediatr Dermatol. Mar-Apr 1996;13(2):175. [Medline].

  16. Piquero-Casals J, Okubo AY, Nico MM. Rothmund-thomson syndrome in three siblings and development of cutaneous squamous cell carcinoma. Pediatr Dermatol. Jul-Aug 2002;19(4):312-6. [Medline].

  17. Howell SM, Bray DW. Amelanotic melanoma in a patient with Rothmund-Thomson syndrome. Arch Dermatol. Mar 2008;144(3):416-7. [Medline].

  18. Broom MA, Wang LL, Otta SK, et al. Successful umbilical cord blood stem cell transplantation in a patient with Rothmund-Thomson syndrome and combined immunodeficiency. Clin Genet. Apr 2006;69(4):337-43. [Medline].

  19. Cheok CF, Bachrati CZ, Chan KL, Ralf C, Wu L, Hickson ID. Roles of the Bloom's syndrome helicase in the maintenance of genome stability. Biochem Soc Trans. Dec 2005;33:1456-9. [Medline].

  20. Houwing RH, Oosterkamp RF, Berghuis M, Beemer FA, Van Vloten WA. Rothmund-Thomson syndrome. Br J Dermatol. Sep 1991;125(3):279-80. [Medline].

  21. Knoell KA, Sidhu-Malik NK, Malik RK. Aplastic anemia in a patient with Rothmund-Thomson syndrome. J Pediatr Hematol Oncol. Sep-Oct 1999;21(5):444-6. [Medline].

  22. Mehollin-Ray AR, Kozinetz CA, Schlesinger AE, Guillerman RP, Wang LL. Radiographic abnormalities in Rothmund-Thomson syndrome and genotype-phenotype correlation with RECQL4 mutation status. AJR Am J Roentgenol. Aug 2008;191(2):W62-6. [Medline].

  23. Moss C. Duplicate reporting of patients with Rothmund-Thomson syndrome. J Am Acad Dermatol. Oct 1989;21(4 Pt 1):815-6. [Medline].

  24. Moss C. Rothmund-Thomson syndrome: a report of two patients and a review of the literature. Br J Dermatol. Jun 1990;122(6):821-9. [Medline].

  25. Nanda A, Kanwar AJ, Kapoor MM, et al. Rothmund-Thomson syndrome in two siblings. Pediatr Dermatol. Dec 1989;6(4):325-8. [Medline].

  26. Narayan S, Fleming C, Trainer AH, Craig JA. Rothmund-Thomson syndrome with myelodysplasia. Pediatr Dermatol. May-Jun 2001;18(3):210-2. [Medline].

  27. Pianigiani E, De Aloe G, Andreassi A, Rubegni P, Fimiani M. Rothmund-Thomson syndrome (Thomson-type) and myelodysplasia. Pediatr Dermatol. Sep-Oct 2001;18(5):422-5. [Medline].

  28. Porter WM, Hardman CM, Abdalla SH, Powles AV. Haematological disease in siblings with Rothmund-Thomson syndrome. Clin Exp Dermatol. Nov 1999;24(6):452-4. [Medline].

  29. Roth DE, Campisano LC, Callen JP, Hersh JH, Yusk JW. Rothmund-Thomson syndrome: a case report. Pediatr Dermatol. Dec 1989;6(4):321-4. [Medline].

  30. Stinco G, Governatori G, Mattighello P, Patrone P. Multiple cutaneous neoplasms in a patient with Rothmund-Thomson syndrome: case report and published work review. J Dermatol. Mar 2008;35(3):154-61. [Medline].

  31. Uhring M, Poterszman A. [DNA helicases and human diseases]. Med Sci (Paris). Dec 2006;22(12):1087-94. [Medline].

  32. Vennos EM, Collins M, James WD. Rothmund-Thomson syndrome: review of the world literature. J Am Acad Dermatol. Nov 1992;27(5 Pt 1):750-62. [Medline].

  33. Wang LL, Levy ML, Lewis RA, et al. Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients. Am J Med Genet. Jul 22 2001;102(1):11-7. [Medline].

 
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Note the poikiloderma and skeletal abnormalities.
Close-up of poikiloderma.
Close-up of poikiloderma.
 
 
 
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