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Rothmund-Thomson syndrome (RTS)

Written2001-10Alessandro Beghini, Lidia Larizza
University of Milan, Medical Faculty, Department of Biology, Genetics for Medical Sciences, via Viotti 5, 20133-Milan, Italy
This article is an update of :
1998-10Lidia Larizza
University of Milan, Medical Faculty, Department of Biology, Genetics for Medical Sciences, via Viotti 5, 20133-Milan, Italy

(Note : for Links provided by Atlas : click)


Other namesPoikiloderma atrophicans and cataract
Atlas_Id 10021
Genes implicated inRECQL4  
Note is a chromosomal instability syndrome with an increased risk of cancers
Inheritance autosomal recessive; rare geno-dermatosis with increased frequency in females; 260 cases reported in the English medical literature.


Note clinical expression highly variable
Phenotype and clinics
  • main features include:
    - growth retardation
    - skin defects appearing within the first year of life (90%) and persisting throuhout life: atrophic dermatosis, poikiloderma, hyperpigmentation, teleangiectasia
    - sparse hair which may progress to partial or total alopecia; dystrophic nails
    - photosensitivity
    - congenital skeletal defects - hypoplasia or absence of the radii and thumbs, osteopenia, cystic or sclerotic changes of the long bones - (>50%); bone age lower than chronological age. PHENOTYPE_AND_CLINICS
    - juvenile cataract, corneal dystrophy (50%)
    - hypodontia
    - hypogonadism (25%)
    - proportionate short stature
    - premature aging

    Detailed definition of the clinical profile in a contemporary cohort of 41 RTS patients evidences some differences in the distribution of the clinical findings (figure 1), which should be kept into account to optimize diagnostic criteria

  • diagnosis : the diagnosis is difficult before the development of the erythema; differential diagnosis with:
    - Werner syndrome,
    - Dyskeratosis congenita,
    - Cockayne syndrome,
    - Bloom syndrome,
    - Fanconi anaemia,
    - Anhidrotic ectodermal dysplasia.
    Neoplastic risk
  • patients have an enhanced risk of bone cancer, specifically osteosarcoma (30 out of 300 - 10%- in the literature) and nonmelanoma skin cancers ( squamous cell carcinoma, basal cell carcinoma) with an estimated prevalence around 5%
  • Etiology: deficiency of RECQL4 helicase (see below), a protein involved in some aspect of replication and transcription, repair and recombination may suggest a mutational mechanism for cancer development, but the specificity for mesenchymal tumors is currently unknown.
  • Treatment only protection against sunlight is possible by means of sunscreens with both UVA and UVB protection; dermatologic therapies; surgical correction of skeletal malformations and cataracts; regular and careful work-up of signs and symptoms of both cutaneous and internal malignancy; caution is warranted in administering chemotherapy to affected individuals due to their sensitivity to chemotherapeutic agents
    Evolution the disease tends to progress during the first years of life, but becomes static so that patients may have a normal lifespan; the mortality from neoplastic disease during the second or third decade is very significantly increased.


    Inborn conditions Spontaneous/induced chromatid breaks were found increased in only a very few studies; In contrast with (mainly negative) chromatid results, consistent clonal/non clonal structural chromosomal abnormalities were evidenced in most studies, often involving chromosome 8, in cultured lymphocytes and in fibroblasts; low frequency trisomy 8 mosaicism has been reported in both lymphocyte and primary fibroblast cultures as well as in uncultured blood and buccal smears, indicating this characteristic chromosomal abnormality is present in vivo; a propensity to centromere misdivision with development of clones carrying isochromosomes, such as i(8q), i(8p), i(12p), i(12q) is peculiar of RTS.
    Cytogenetics of cancer marked chromosomal instability has been detected in mesenchymal tumours developed by RTS sibs

    Other findings

    Note reduced unscheduled DNA synthesis, 37% of normal after exposure to ultraviolet C or gamma irradiation

    Genes involved and Proteins

    Note Mutations of RECQL4 gene, a member of the RECQ helicase genefamily, have been identified in a limited number of RTS patients. Molecular testing is available on a research basis and useful in confirming the diagnosis in suspected RTS patients carrying RECQL4 mutations.


    Clonal lines of aneuploid cells in Rothmund-Thomson syndrome.
    Der Kaloustian VM, McGill JJ, Vekemans M, Kopelman HR
    American journal of medical genetics. 1990 ; 37 (3) : 336-339.
    PMID 2260560
    Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome.
    Kitao S, Shimamoto A, Goto M, Miller RW, Smithson WA, Lindor NM, Furuichi Y
    Nature genetics. 1999 ; 22 (1) : 82-84.
    PMID 10319867
    Rothmund-Thomson syndrome in siblings: evidence for acquired in vivo mosaicism.
    Lindor NM, Devries EM, Michels VV, Schad CR, Jalal SM, Donovan KM, Smithson WA, Kvols LK, Thibodeau SN, Dewald GW
    Clinical genetics. 1996 ; 49 (3) : 124-129.
    PMID 8737976
    Rothmund-Thomson syndrome due to RECQ4 helicase mutations: report and clinical and molecular comparisons with Bloom syndrome and Werner syndrome.
    Lindor NM, Furuichi Y, Kitao S, Shimamoto A, Arndt C, Jalal S
    American journal of medical genetics. 2000 ; 90 (3) : 223-228.
    PMID 10678659
    Chromosomal instability in fibroblasts and mesenchymal tumors from 2 sibs with Rothmund-Thomson syndrome.
    Miozzo M, Castorina P, Riva P, Dalprà L, Fuhrman Conti AM, Volpi L, Hoe TS, Khoo A, Wiegant J, Rosenberg C, Larizza L
    International journal of cancer. Journal international du cancer. 1998 ; 77 (4) : 504-510.
    PMID 9679749
    Instability of lymphocyte chromosomes in a girl with Rothmund-Thomson syndrome.
    Orstavik KH, McFadden N, Hagelsteen J, Ormerod E, van der Hagen CB
    Journal of medical genetics. 1994 ; 31 (7) : 570-572.
    PMID 7966195
    A case of Rothmund-Thomson syndrome with reduced DNA repair capacity.
    Shinya A, Nishigori C, Moriwaki S, Takebe H, Kubota M, Ogino A, Imamura S
    Archives of dermatology. 1993 ; 129 (3) : 332-336.
    PMID 8447670
    Enhanced radiosensitivity and defective DNA repair in cultured fibroblasts derived from Rothmund Thomson syndrome patients.
    Smith PJ, Paterson MC
    Mutation research. 1982 ; 94 (1) : 213-228.
    PMID 7099192
    Rothmund-Thomson syndrome: review of the world literature.
    Vennos EM, Collins M, James WD
    Journal of the American Academy of Dermatology. 1992 ; 27 (5 Pt 1) : 750-762.
    PMID 1430398
    Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients.
    Wang LL, Levy ML, Lewis RA, Chintagumpala MM, Lev D, Rogers M, Plon SE
    American journal of medical genetics. 2001 ; 102 (1) : 11-17.
    PMID 11471165
    Rothmund-Thomson syndrome associated with trisomy 8 mosaicism.
    Ying KL, Oizumi J, Curry CJ
    Journal of medical genetics. 1990 ; 27 (4) : 258-260.
    PMID 2325107
    DNA helicases, genomic instability, and human genetic disease.
    van Brabant AJ, Stan R, Ellis NA
    Annual review of genomics and human genetics. 2000 ; 1 : 409-459.
    PMID 11701636


    This paper should be referenced as such :
    Beghini, A ; Larizza, L
    Rothmund-Thomson syndrome (RTS)
    Atlas Genet Cytogenet Oncol Haematol. 2002;6(1):59-61.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :
    History of this paper:
    Larizza, L. Rothmund-Thomson syndrome (RTS). Atlas Genet Cytogenet Oncol Haematol. 1999;3(1):50-51.

    Other genes implicated (Data extracted from papers in the Atlas) [ 5 ]


    External links

    OrphanetRothmund-Thomson syndrome
    Other databaseRothmund-Thomson syndrome (GARD)
    Other databaseRothmund Thomson Syndrome - NORD
    Other databaseRothmund-Thomson Syndrome - GeneClinics
    Genes implicated inRECQL4   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  

    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed

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