Rothmund-Thomson syndrome type 2

Rothmund-Thomson syndrome type 2 (RTS2) is a rare autosomal recessive genodermatosis caused by biallelic pathogenic variants in the RECQL4 gene, which encodes a RecQ family DNA helicase involved in DNA replication and repair. RTS2 is distinguished from Rothmund-Thomson syndrome type 1 (caused by ANAPC1 variants) primarily by its association with an increased risk of osteosarcoma. The hallmark feature of RTS2 is poikiloderma — a characteristic skin rash that typically appears in infancy (between 3 and 6 months of age), initially presenting as erythema 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, and areas of hyper- and hypopigmentation. Beyond the skin, RTS2 affects multiple body systems. Skeletal abnormalities are common and may include small stature, radial ray defects, absent or hypoplastic thumbs, and other limb anomalies. Sparse or absent hair (including scalp hair, eyebrows, and eyelashes), sparse or absent eyelashes, juvenile cataracts (though these are more characteristic of type 1), and dental anomalies may also occur. A key distinguishing feature of RTS2 is the significantly elevated risk of osteosarcoma, which typically develops in childhood or adolescence. Some patients may also have an increased risk of skin cancer. Other features can include gastrointestinal problems, such as chronic diarrhea and vomiting in infancy, and hematologic abnormalities including bone marrow failure in some cases. There is currently no cure or disease-specific treatment for Rothmund-Thomson syndrome type 2. Management is supportive and multidisciplinary, involving dermatologists, orthopedic surgeons, oncologists, and other specialists. Sun protection is strongly recommended to minimize skin damage. Regular surveillance for osteosarcoma and other malignancies is a critical component of care. Skeletal abnormalities may require orthopedic intervention, and standard oncologic protocols are used if osteosarcoma develops. Genetic counseling is recommended for affected families.

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