Rothmund-Thomson syndrome (RTS, OMIN #268400) is a rare hereditary chromosome instability syndrome, resulting in a cancer predisposition syndrome that is associated with an increased incidence of osteosarcomas. A characteristic feature in the acute phase is classic erythema, which develops into poikiloderma over the course of several years.

Key Data

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Synonym RTS
Genes Type 1 RTS -> unknown
Type 2 RTS -> RECQL4
Gene products RECQL4: ATP-dependent DNA helicase Q4
Function Part of the RECQ helicase enzymes that unwind the DNA double helix. RECQL4 is involved in the process of DNA replication, DNA repair, telomere preservation, and mitochondrial DNA integrity.
Heredity Autosomal recessive
Prevalence Unknown (fewer than 400 cases known worldwide)
Genotype-phenotype correlation Unknown
Penetrance Unknown
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Characteristic clinical symptoms and molecular genetic evidence of a biallelic/homozygous pathogenic variant in RECQL4

Method: single-gene testing, multiple-gene panel, exome/genome sequencing

Differential Diagnoses

Clinical Presentation

Acute Phase

Normal skin at birth. Onset of erythema at the age of 3-6 months, which spreads from apical (face) to distal regions (buttocks and extremities), typically not affecting the trunk, and is accompanied by the formation of blisters.

Chronic Phase

Over the course of months or years, development of consecutive pigment changes, dermal atrophy, hypertrophy, and telangiectasia (poikiloderma), which persist throughout life.

  • Poikiloderma (hyperpigmentation, hypopigmentation, atrophy, telangiectasia)

  • Sparse hair, eyebrows, and eyelashes

  • Hyperkeratosis (especially on the soles of the feet)

  • Nail changes (dysplastic, poorly formed)

  • Symmetrical dwarfism

  • Gastrointestinal problems (eating disorders, chronic vomiting/diarrhea)

  • Skeletal defects (defects of the radius and ulna, absent or hypoplastic patella, osteopenia)

  • Osteoporosis

  • Dental abnormalities (rudimentary development, hypoplasia, enamel defects)

  • Cataract (juvenile, bilateral)

  • Bone marrow failure

Predisposition to Cancer (Only in Type 2 RTS), Entities:

  • Osteosarcoma, with an earlier predilection age than in the general population

  • Basal cell carcinomas

  • Squamous epithelial carcinomas

  • MDS

  • Lymphomas

  • Leukemia

Genetically Related Syndromes:

RAPADILINO syndrome: Autosomal recessive hereditary disease in the Finnish population associated with pigment changes (café au lait spots, no poikiloderma), dwarfism, defects of the palate, defects of the radius, patellar hypoplasia, gastrointestinal abnormalities, and an increased incidence of osteosarcomas and lymphomas. It is caused by pathological variants in RECLQ4 (primarily homozygosity for IVS7+2delT [Fin-major]).

Therapeutic Considerations

  • Avoidance of exposure to ionizing radiation

  • Avoidance of excessive exposure to sunlight

  • Consistent sun protection measures (UV-A and UV-B protection)

  • Possibility of retinoids for hyperkeratosis

  • Calcium and vitamin D supplementation for osteopenia and for condition following a fracture

  • Pulsed laser therapy for telangiectasia

Surveillance Recommendations

Surveillance Recommendations

Evidence-based standards are lacking for early detection, particularly during childhood. The AACR consensus recommendations are listed below.

  • Hematology-oncology: medical history and physical examination, clarification about the risk of osteosarcoma with type 2 RTS, imaging according to the clinical symptoms (no evidence that routine screening is necessary), HPV vaccination

  • Dermatology: annual skin examination, limited exposure to sunlight, and early intervention if there are findings that require treatment

  • Ophthalmology: annual cataract screening, treatment if necessary

  • Endocrinology: treatment for osteopenia

  • Orthopedics: basic X-ray evaluation before the age of 5

  • Dental: six-monthly checkups with competent treatment of any hypoplastic teeth and dental enamel defects

Additional Information

Open Clinical Trials / Registries

There are currently no ongoing clinical trials/registries for patients with Rothmund-Thomson syndrome that we can recommend to you for more information.

Support Groups