Rothmund-Thomson Syndrome – Definition

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.

Synonym:

RTS

Gene:

Type 1 RTS -> unknown

Type 2 RTS -> RECQL4

Gene ­product:

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.

Pattern of inheritance:

Autosomal recessive

Prevalence:

Unknown (less than 400 known cases worldwide)

Genotype-phenotype correlation:

Unknown

Penetrance:

Unknown

Overview of the Chapters on This Page:

  • Rothmund-Thomson Syndrome – Definition (This Section)
  • Rothmund-Thomson Syndrome – Diagnosis

  • Clinical Presentation

  • Special Features of Treatment

  • Recommendations for Early Detection in Your Patients

  • Further Information (e.g., Links to Support Groups)

  • Rothmund-Thomson Syndrome – Definition (This Section)
  • Rothmund-Thomson Syndrome – Diagnosis

  • Clinical Presentation

  • Special Features of Treatment

  • Recommendations for Early Detection in Your Patients

  • Further Information (e.g., Links to Support Groups)

Rothmund-Thomson Syndrome – Diagnosis

Diagnostics

  • 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

The development of consecutive pigmentary changes, dermal atrophy, hypertrophy, and telangiectasia (poikiloderma), which persist for life, occurs over months to years.

  • Poikiloderma (hyperpigmentation, hypopigmentation, atrophy, telangiectasia)
  • Thinning hair, thinning eyebrows and eyelashes
  • Hyperkeratosis (especially soles of the feet)
  • Nail changes (dysplastic, poorly formed)
  • Symmetrical short stature
  • Gastrointestinal problems (nutritional disorders, chronic vomiting/diarrhea)
  • Skeletal defects (radius and ulna defects, missing or hypoplastic patella, osteopenia)
  • Osteoporosis
  • Dental abnormalities (rudimentary anlage, hypoplasia, enamel defects)
  • Cataract (juvenile, bilateral)
  • Bone marrow failure

Cancer Predisposition (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]).

Special Features of Treatment

  • 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 condition following a fracture
  • Pulsed laser therapy for telangiectasia

Diagnosis of Rothmund-Thomson Syndrome- What's Next?

Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.

Diagnosis of Rothmund-Thomson Syndrome- What's Next?

Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.

Recommendations for Early Detection in Your Patients

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

Rothmund-Thomson Syndrome – Further Information

Open Clinical Trials/ Registries

Additional Resources