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Rothmund-Thomson syndrome (RTS) is a genodermatosis presenting with a characteristic facial rash (poikiloderma) associated with short stature due to pre- and postnatal growth delay, sparse scalp hair, sparse or absent eyelashes and/or eyebrows, juvenile cataracts, skeletal abnormalities, radial ray defects, premature aging and a predisposition to certain cancers.
ORPHA:2909Classification level: Disorder
The prevalence is unknown, but around 300 cases have been reported so far.
The skin is usually normal at birth but erythema develops on the cheeks at 3-6 months of age and subsequently spreads to the extremities and buttocks. The trunk and abdomen are generally spared. During the course of the disease, cutaneous atrophy with reticulated areas of hypo- and hyperpigmentation and persistent telangiectasias develop. Other cutaneous manifestations include dental anomalies, nail dystrophy and palmo-plantar hyperkeratotic lesions. The extracutaneous manifestations are clinically heterogeneous and two subforms of RTS have been defined: RTS type 1 (RTS1; see this term) characterized by poikiloderma, ectodermal dysplasia and juvenile cataracts, and RTS type 2 (RTS2; see this term) characterized by poikiloderma, congenital bone defects (frontal bossing, saddle nose and radial ray defects: thumb hypo- or aplasia or radial aplasia) and an increased risk of osteosarcoma (see this term) in childhood and cutaneous squamous cell carcinoma later in life. Gastrointestinal (chronic emesis and diarrhea), respiratory, and benign and malignant hematological manifestations (anemia, neutropenia and myelodysplasia), as well as hypogonadism and osteopenia, have been reported in some patients.
RTS2 is caused by homozygous or compound heterozygous mutations in the RECQL4 helicase gene (8q24.3; detected in 60-65% of RTS patients), whereas the etiology in RTS1 remains unknown.
Diagnosis is based on clinical findings (primarily on the age of onset, spreading and appearance of the poikiloderma) and molecular analysis for RECQL4 mutations. The diagnosis of RTS should be considered in all patients with osteosarcoma, particularly if associated with skin changes.
The differential diagnosis should include other causes of childhood poikiloderma and other rare genodermatoses with prominent telangiectasias (including Bloom syndrome, xeroderma pigmentosum, Kindler syndrome, poikiloderma with neutropenia, and dyskeratosis congenita; see these terms), and the allelic disorders, RAPADILINO syndrome (in which radial ray defects are a constant feature, poikiloderma is absent and the risk of malignancy is lower) and Baller-Gerold syndrome (which is associated with craniosynostosis; see these terms).
RTS is transmitted in an autosomal recessive manner. Genetic counseling should be provided for RTS patients and their families, together with a recommendation for cancer surveillance for all patients with RTS2.
Management and treatment
Management should include laser treatment for the telangiectatic lesions, annual ophthalmic examinations and a radiological survey in case of bone pain, limping or fractures (indicators of osteosarcoma). RTS patients may show increased susceptibility to the adverse effects of chemotherapy, and a higher risk of a secondary malignancy (5% risk of developing skin cancer).
The prognosis in RTS is variable: life expectancy is normal in the absence of cancer, whereas outcomes in patients with malignant pathologies depend on the quality and frequency of cancer screening and treatment.