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.
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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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
Over the course of months or years, development of consecutive pigment changes, dermal atrophy, hypertrophy, and telangiectasia (poikiloderma), which persist throughout life.
Predisposition to Cancer (Only in Type 2 RTS), Entities:
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
Surveillance Recommendations
Surveillance Recommendations
Evidence-based standards are lacking for early detection, particularly during childhood. The AACR consensus recommendations are listed below.
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.