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Rothmund-Thomson Syndrome Clinical Presentation

  • Author: Sylvia Hsu, MD; Chief Editor: Dirk M Elston, MD  more...
Updated: Mar 30, 2016


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.



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]



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, 11, 12, 13, 14, 15] 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.

Contributor Information and Disclosures

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

Disclosure: Nothing to disclose.


Saira J George, MD Assistant Professor of Dermatology, The University of Texas MD Anderson Cancer Center

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

Disclosure: Nothing to disclose.

Specialty Editor Board

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

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

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

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

Disclosure: Nothing to disclose.

Additional Contributors

Andrea Leigh Zaenglein, MD Professor of Dermatology and Pediatrics, Department of Dermatology, Hershey Medical Center, Pennsylvania State University College of Medicine

Andrea Leigh Zaenglein, MD is a member of the following medical societies: American Academy of Dermatology, Society for Pediatric Dermatology

Disclosure: Received consulting fee from Galderma for consulting; Received consulting fee from Valeant for consulting; Received consulting fee from Promius for consulting; Received consulting fee from Anacor for consulting; Received grant/research funds from Stiefel for investigator; Received grant/research funds from Astellas for investigator; Received grant/research funds from Ranbaxy for other; Received consulting fee from Ranbaxy for consulting.

  1. Kitao S, Shimamoto A, Goto M, et al. Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome. Nat Genet. 1999 May. 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. 1999 Nov 1. 61(3):268-76. [Medline].

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  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. 2008 Nov-Dec. 18(6):632-4. [Medline].

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  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. 2006 Jun 23. 345(1):403-9. [Medline].

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  14. Ferrarelli LK, Popuri V, Ghosh AK, Tadokoro T, Canugovi C, Hsu JK, et al. The RECQL4 protein, deficient in Rothmund-Thomson syndrome is active on telomeric D-loops containing DNA metabolism blocking lesions. DNA Repair (Amst). 2013 Jul. 12(7):518-28. [Medline]. [Full Text].

  15. Gupta S, De S, Srivastava V, Hussain M, Kumari J, Muniyappa K, et al. RECQL4 and p53 potentiate the activity of polymerase ? and maintain the integrity of the human mitochondrial genome. Carcinogenesis. 2014 Jan. 35(1):34-45. [Medline].

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

  17. 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. 2008 Aug. 191(2):W62-6. [Medline].

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  20. Zils K, Klingebiel T, Behnisch W, Mueller HL, Schlegel PG, Fruehwald M, et al. Osteosarcoma in patients with Rothmund-Thomson syndrome. Pediatr Hematol Oncol. 2015 Feb. 32 (1):32-40. [Medline].

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