Rothmund-Thomson syndrome (RTS) is characterized by poikiloderma; sparse hair, eyelashes, and/or eyebrows/lashes; small stature; skeletal and dental abnormalities; cataracts; and an increased risk for cancer, especially osteosarcoma. The skin is typically normal at birth; the rash of RTS develops between age three and six months as erythema, swelling, and blistering on the face and subsequently spreads to the buttocks and extremities. The rash evolves over months to years into the chronic pattern of reticulated hypo- and hyperpigmentation, punctate atrophy, and telangiectases, collectively known as poikiloderma. Hyperkeratotic lesions occur in approximately one-third of individuals. Skeletal abnormalities include dysplasias, absent or malformed bones (such as absent radii), osteopenia, and delayed bone formation.
The diagnosis of RTS is established by clinical findings - in particular, the characteristic rash. Routine cytogenetic studies of lymphocytes or skin fibroblasts may reveal mosaic abnormalities of chromosome 8, such as trisomy 8, partial 8q duplication, and tetrasomy 8q, which have been seen in individuals with RTS but are not diagnostic. Skin biopsy may show poikilodermatous changes, which are nonspecific but consistent with RTS. RECQL4 is the only gene associated with RTS to date; although evidence suggests genetic heterogeneity, no other locus for RTS has been identified. Molecular testing of RECQL4 is clinically available.
RTS is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutations in the family are known.