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
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
- Bloom syndrome
- Werner syndrome (WRN)
- Fanconi anemia
- Ataxia-telangiectasia
- Xeroderma pigmentosum
- Kindler syndrome (FERMT1 (KIND1))
- Dyskeratosis congenita
- Poikiloderma with neutropenia (USB1)
- POIKTMP syndrome (FAM111B)
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
Oncology
- Awareness of tumour-related symptoms from the time of diagnosis
- Good sun protection and avoidance of ionising radiation
- HPV vaccination
- Full physical examination every year after diagnosis
- For RTS type 2 (pathogenic variant in RECQL4): Consider whole-body MRI annually from diagnosis
Dermatology
- Dermatological examination from diagnosis annually
Orthopaedics
- Basic radiological evaluation for skeletal anomalies before the age of 5 years
Ophthalmology
- Annual cataract screening; therapy if necessary
Dentistry
- Six-monthly check-ups with treatment of any hypoplastic teeth and enamel defects
