FaCD Online Syndrome Fact Sheet

Last updated: 05 Jun 2009

Name: Rothmund-Thomson syndrome

Synonym: RTS, Poikiloderma Atrophicans and Cataract, Congenital Poikiloderma

Mode of Inheritance: AR

OMIM number: 268400  


RECQL4, mapped to 8q24.3

Tumor features

bone, malignant fibrous histiocytoma of the
myelodysplastic syndrome (MDS)

Tumor features (possible)

leukemia, acute myeloblastic (AML, M2)
melanoma, cutaneous
non-Hodgkin lymphoma
parathyroid adenoma
skin cancer, basal cell
skin cancer, squamous cell
skin, eccrine poroma (malignant)

Non-tumor features

cataract, juvenile
dental abnormalities
eye brows/lashes, sparse/absent
ionizing radiation sensitivity, increased
nails, dystrophic
radial hypoplasia
short stature
ulnar hypoplasia


The hallmarks of this disorder are congenital poikiloderma of face and limbs, juvenile cataracts and a range of skeletal anomalies, including small stature, radial or ulnar hypoplasia, fibrous dysplasia, irregular cortical hyperostosis and osteoporosis.[1].

Osteosarcoma has been observed in 12 out of 200 Rothmund-Thomson cases[3] and 18 out of 42 with proven RECQL4 mutation[24]. The incidence of osteosarcoma was 0.05 per year in RECQL4 truncating mutation-positive patients[25]. The most frequently involved site is the tibia. Age of onset of the tumor ranged from 5 to 32 years (most cases between 9-13 years).[2-5]. Some cases are multicentric[6]. Hicks et al.[19] suggest that the clinical behavior of osteosarcoma in RTS is similar to patients with sporadic osteosarcoma.

Malignant Fibrous Histiocytomas has been reported in a few cases[7,8,23]. A parathyroid adenoma was observed in one case[9]. Several skin tumors have been reported: melanoma[12], basal and squamous cell skin cancer[13,14], Bowen's disease[13] and malignant eccrine poroma[15]. Squamous cell carcinoma of the tongue[16,20], nasopharyngeal non-Hodgkin's lymphoma[22], myelodysplasia[17,18] and AML[21] have been reported as well.

Increased radiation sensitivity has been suggested by some authors[5;10]. However, other primary fibroblasts from RTS patients showed no sensitivity to a wide variety of genotoxic agents, including ionizing and UV radiation[11].


[1] Taylor WB. Rothmund's syndrome- Thomson's syndrome: congenital poikiloderma with or without juvenile cateracts; a review of the literature, report of a case, and discussion of the relationship of the two syndromes. Arch Dermatol 1957; 75:236-244.
[2] Leonard A, Craft AW, Moss C, Malcolm AJ. Osteogenic sarcoma in the Rothmund-Thomson syndrome. Med Pediatr Oncol 1996; 26(4):249-253.
[3] Drouin CA, Mongrain E, Sasseville D, Bouchard HL, Drouin M. Rothmund-Thomson syndrome with osteosarcoma. J Am Acad Dermatol 1993; 28:301-305.
[4] Kozel MMA, Sillevis JH, Caron HN. Rothmund-Thomson syndrome and the development of malignant bone tumors. Europ.Soc.Ped.Dermatol. V th congres, 83. 1996. Ref Type: Abstract
[5] Varughese M, Leavey P, Smith P, Sneath R, Breatnach F, O'Meara A. Osteogenic sarcoma and Rothmund Thomson syndrome. J Cancer Res Clin Oncol 1992; 118(5):389-390.
[6] El-Khoury JM, Haddad SN, Atallah NG. Osteosarcomatosis with Rothmund-Thomson syndrome. Br J Radiol 1997; 70:215-218.
[7] Ilhan I, Arikan U, Buyukpamukcu M. Rothmund-Thomson syndrome and malignant fibrous histiocytoma: a case report [letter]. Pediatr Hematol Oncol 1995; 12(1):103-105.
[8] Ferguson PC, Griffin AM, Bell RS. Primary patellar tumors. Clin Orthop 1997;(336):199-204.
[9] Werder EA, Murset G, Illig R, Prader A. Hypogonadism and parathyroid adenoma in congenital poikiloderma (Rothmund-Thomson syndrome). Clin Endocrinol Oxf 1975; 4(1):75-82.
[10] Smith PJ, Paterson MC. Enhanced radiosensitivity and defective DNA repair in cultured fibroblasts derived from Rothmund Thomson syndrome patients. Mutat Res 1982; 94(1):213-228.
[11] Cabral RE, Queille S, Bodemer C, de Prost Y, Neto JB, Sarasin A, Daya-Grosjean L. Identification of new RECQL4 mutations in Caucasian Rothmund-Thomson patients and analysis of sensitivity to a wide range of genotoxic agents. Mutation research 2008; 643(1-2):41-47.
[12] Howell SM, Bray DW. Amelanotic melanoma in a patient with Rothmund-Thomson syndrome. Archives of dermatology 2008; 144(3):416-7.
[13] Stinco G, Governatori G, Mattighello P, Patrone P. Multiple cutaneous neoplasms in a patient with Rothmund-Thomson syndrome: case report and published work review. The Journal of dermatology 2008; 35(3):154-61.
[14] Marín-Bertolín S, Amorrortu-Velayos J, Aliaga Boniche A. Squamous cell carcinoma of the tongue in a patient with Rothmund-Thomson syndrome. British journal of plastic surgery 1998; 51(8):646-8.
[15] Piquero-Casals J, Okubo AY, Nico MM. Rothmund-thomson syndrome in three siblings and development of cutaneous squamous cell carcinoma. Pediatric dermatology 2002 Jul-Aug; 19(4):312-6.
[16] Van Hees CL, Van Duinen CM, Bruijin JA, Vermeer BJ. Malignant eccrine poroma in a patient with Rothmund-Thomson syndrome. The British journal of dermatology 1996; 134(4):813-5.
[17] Narayan S, Fleming C, Trainer AH, Craig JA. Rothmund-Thomson syndrome with myelodysplasia. Pediatric dermatology 2001 May-Jun; 18(3):210-2.
[18] Pianigiani E, De Aloe G, Andreassi A, Rubegni P, Fimiani M. Rothmund-Thomson syndrome (Thomson-type) and myelodysplasia. Pediatric dermatology 2001 Sep-Oct; 18(5):422-5.
[19] Hicks MJ, Roth JR, Kozinetz CA, Wang LL. Clinicopathologic features of osteosarcoma in patients with Rothmund-Thomson syndrome. Journal of clinical oncology 2007; 25(4):370-5.
[20] Dahele MR, Benton EC, Hennessy A, MacDougall RH, Price A, Mitchell R, Watson J. A patient with Rothmund-Thomson syndrome and tongue cancer--experience of radiation toxicity. Clinical oncology 2004; 16(5):371-2.
[21] Porter WM, Hardman CM, Abdalla SH, Powles AV. Haematological disease in siblings with Rothmund-Thomson syndrome. Clinical and experimental dermatology 1999; 24(6):452-4.
[22] Spurney C, Gorlick R, Meyers PA, Healey JH, Huvos AG. Multicentric osteosarcoma, Rothmund-Thomson syndrome, and secondary nasopharyngeal non-Hodgkin's lymphoma: a case report and review of the literature. Journal of pediatric hematology/oncology 1998 Sep-Oct; 20(5):494-7.
[23] Miozzo M, Castorina P, Riva P, Dalprà L, Fuhrman Conti AM, Volpi L, Hoe TS, Khoo A, Wiegant J, Rosenberg C, Larizza L. Chromosomal instability in fibroblasts and mesenchymal tumors from 2 sibs with Rothmund-Thomson syndrome 1998; 77(4):504-10.
[24] Siitonen HA, Sotkasiira J, Biervliet M, Benmansour A, Capri Y, Cormier-Daire V, Crandall B, Hannula-Jouppi K, Hennekam R, Herzog D, Keymolen K, Lipsanen-Nyman M, Miny P, Plon SE, Riedl S, Sarkar A, Vargas FR, Verloes A, Wang LL, Kääriäinen H, Kestilä M. The mutation spectrum in RECQL4 diseases. Eur J Hum Genet. 2009 Feb;17(2):151-8
[25] Wang LL, Gannavarapu A, Kozinetz CA, Levy ML, Lewis RA, Chintagumpala MM, Ruiz-Maldanado R, Contreras-Ruiz J, Cunniff C, Erickson RP, Lev D, Rogers M, Zackai EH, Plon SE. Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. J Natl Cancer Inst. 2003 May 7;95(9):669-74