Clinical characteristics: Rothmund-Thomson syndrome (RTS) is characterized by a rash that progresses to poikiloderma; sparse hair, eyelashes, and/or eyebrows; small size; skeletal and dental abnormalities; juvenile cataracts; and an increased risk for cancer, especially osteosarcoma. A variety of benign and malignant hematologic abnormalities have been reported in affected individuals. The rash of RTS typically develops between ages three and six months (occasionally as late as age two years) as erythema, swelling, and blistering on the face, subsequently spreading to the buttocks and extremities. The rash evolves over months to years into the chronic pattern of reticulated hypo- and hyperpigmentation, telangiectasias, and punctate atrophy (collectively known as poikiloderma) that persist throughout life. Hyperkeratotic lesions occur in approximately one third of individuals. Skeletal abnormalities can include radial ray defects, ulnar defects, absent or hypoplastic patella, and osteopenia.
Diagnosis/testing: The diagnosis of RTS is established by clinical findings (in particular, the characteristic rash) and/or the identification of biallelic pathogenic variants in ANAPC1 or RECQL4 on molecular genetic testing.
Management: Treatment of manifestations: Pulsed dye laser to the telangiectatic component of the rash for cosmetic management; surgical removal of cataracts; standard treatment for cancer and/or hematologic concerns.
Surveillance: Annual general physical, dermatologic, and eye examination; monitoring of health and growth, skin for lesions with unusual color or texture, for cataracts. Prompt skeletal radiographic examination when clinical suspicion of osteosarcoma is present (bone pain, swelling or enlarging lesion on a limb); however, surveillance screening for osteosarcoma is not routinely recommended.
Agents/circumstances to avoid: Excessive exposure to heat or sunlight; growth hormone for those with short stature with normal growth hormone levels.
Genetic counseling: 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. Carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible if the ANAPC1 or RECQL4 pathogenic variants in the family are known.
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