Rothmund-Thomson syndrome

Rothmund-Thomson syndrome (RTS), also known as poikiloderma congenitale, is a rare autosomal recessive genodermatosis characterized by a distinctive skin rash (poikiloderma), skeletal abnormalities, and an increased risk of cancer. The condition is primarily caused by biallelic pathogenic variants in the RECQL4 gene (RTS type 2), which encodes a DNA helicase important for genome stability. A second form (RTS type 1) has been associated with variants in the ANAPC1 gene. The hallmark feature is poikiloderma — a rash that typically appears between 3 and 6 months of age, initially presenting as redness and swelling on the cheeks before spreading to the extremities and buttocks. Over time, the rash evolves into a chronic pattern of skin atrophy, telangiectasias (dilated blood vessels), and areas of increased and decreased pigmentation. The syndrome affects multiple body systems. Skeletal abnormalities are common and include small stature, radial ray defects (absent or malformed thumbs and radius bones), and osteopenia. Patients may also develop sparse or absent hair (including scalp hair, eyebrows, and eyelashes), sparse or absent eyelashes, juvenile cataracts (particularly in RTS type 1), small or malformed teeth, and gastrointestinal problems such as chronic diarrhea and vomiting in infancy. Importantly, individuals with RECQL4 mutations (RTS type 2) have a significantly elevated risk of osteosarcoma, typically developing in childhood or adolescence, and may also have an increased risk of skin cancer. There is currently no cure or disease-specific treatment for Rothmund-Thomson syndrome. Management is supportive and multidisciplinary, involving dermatologists, orthopedic specialists, ophthalmologists, oncologists, and geneticists. Sun protection is strongly recommended to minimize skin damage. Regular cancer surveillance, particularly screening for osteosarcoma, is essential for patients with RECQL4 mutations. Cataracts may require surgical intervention. Growth and nutritional support may be needed during childhood. Genetic counseling is recommended for affected families to discuss recurrence risks and family planning options.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Rothmund-Thomson syndrome