Rothmund-Thomson syndrome (RTS)

2001-10-01   Alessandro Beghini , Lidia Larizza 

University of Milan, Medical Faculty, Department of Biology, Genetics for Medical Sciences, via Viotti 5, 20133-Milan, Italy



Rothmund-Thomson syndrome (RTS)


Poikiloderma atrophicans and cataract


is a chromosomal instability syndrome with an increased risk of cancers


autosomal recessive; rare geno-dermatosis with increased frequency in females; 260 cases reported in the English medical literature.






2909 Rothmund-Thomson syndrome




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.\tPHENOTYPE_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.
  • Atlas Image

    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


    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 condition

    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.

    Cancer cytog

    marked chromosomal instability has been detected in mesenchymal tumours developed by RTS sibs

    Other Findings


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

    Genes involved and Proteins

    To be noted


    http:\/\/\/cgi-win\/nord.exe?proc=GetDocument&rectype=0&recnum=694 Rothmund Thomson Syndrome - NORDhttp:\/\/\/profiles\/rts Rothmund-Thomson Syndrome - GeneClinics


    Pubmed IDLast YearTitleAuthors
    22605601990Clonal lines of aneuploid cells in Rothmund-Thomson syndrome.Der Kaloustian VM et al
    103198671999Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome.Kitao S et al
    87379761996Rothmund-Thomson syndrome in siblings: evidence for acquired in vivo mosaicism.Lindor NM et al
    106786592000Rothmund-Thomson syndrome due to RECQ4 helicase mutations: report and clinical and molecular comparisons with Bloom syndrome and Werner syndrome.Lindor NM et al
    96797491998Chromosomal instability in fibroblasts and mesenchymal tumors from 2 sibs with Rothmund-Thomson syndrome.Miozzo M et al
    79661951994Instability of lymphocyte chromosomes in a girl with Rothmund-Thomson syndrome.Orstavik KH et al
    84476701993A case of Rothmund-Thomson syndrome with reduced DNA repair capacity.Shinya A et al
    70991921982Enhanced radiosensitivity and defective DNA repair in cultured fibroblasts derived from Rothmund Thomson syndrome patients.Smith PJ et al
    14303981992Rothmund-Thomson syndrome: review of the world literature.Vennos EM et al
    114711652001Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients.Wang LL et al
    23251071990Rothmund-Thomson syndrome associated with trisomy 8 mosaicism.Ying KL et al
    117016362000DNA helicases, genomic instability, and human genetic disease.van Brabant AJ et al