Rothmund-Thomson Syndrome Clinical Presentation
- Author: Sylvia Hsu, MD; Chief Editor: Dirk M Elston, MD more...
Patients with Rothmund-Thomson syndrome (poikiloderma congenitale) generally present with a rash (poikiloderma), small stature, and skeletal dysplasias.
The characteristic skin findings are the most consistent feature of the syndrome. The acute phase begins in early infancy as red patches or edematous plaques, sometimes with blistering. The cheeks are usually first involved, with later spread to other areas of the face, the extremities, and the buttocks. Over months to years, the rash enters a chronic stage characterized by poikiloderma (atrophy, telangiectasias, and pigmentary changes).
Photosensitivity is a feature in more than 30% of cases.
Gastrointestinal problems such as chronic emesis or diarrhea may occur in infancy and early childhood but usually resolve spontaneously. Celiac disease has been reported.
Hematological abnormalities ranging from isolated anemia and neutropenia to myelodysplasia and leukemia have also been noted to occur.
In Rothmund-Thomson syndrome (poikiloderma congenitale), irregular erythema and edema of the skin is replaced by reticulated red-brown patches associated with punctate atrophy and telangiectasias (poikiloderma). These characteristic skin changes are typically seen on the face, extensor extremities, and buttocks with sparing of the chest, abdomen, and back. See the images below.
Acral hyperkeratotic lesions on the elbows, knees, hands, and feet can be seen at puberty. Palmar keratoderma has been reported.
Patients may have sparse scalp hair, eyelashes, and eyebrows. Premature canities may also be observed.
Nail abnormalities such as dystrophic or atrophic nails may be seen.
Dental abnormalities include malformation, microdontia, and failure of eruption.
Juvenile cataracts have been reported to occur with a prevalence that has been estimated at less than 10% in some series and as high as 40-50% in others. Most develop between age 3 and 7 years.
Patients usually have short stature, which ranges from dwarfism to a small build. More than half of patients have skeletal abnormalities, most frequently a characteristic facies (with frontal bossing, saddle nose, and micrognathia), disproportionately small hands and feet, absent or malformed radii, and absent or partially formed thumbs.
Sexual abnormalities, affecting about 25% of adult patients, include hypoplasia and/or aplasia of the external genitalia, amenorrhea, lack of secondary sex characteristics, and infertility.
Otsu et al report a patient who had some uncommon complications of Rothmund-Thomson syndrome (poikiloderma congenitale) and many typical features, but the patient did not have a mutation in RECQL4; therefore, they suggest this case was a "peculiar" variant of Rothmund-Thomson syndrome.
Rothmund-Thomson syndrome (poikiloderma congenitale) has been attributed to mutations of the RECQL4 gene on 8q24, which encodes a RecQ DNA helicase.[1, 2, 3, 8] RecQ helicases are enzymes that function in DNA replication and repair and appear to be essential for the maintenance of genomic stability.[9, 10, 11, 12, 13, 14, 15] A strong correlation appears to exist between the presence of truncating, loss-of-function mutations of the RECQL4 gene, and the development of skeletal abnormalities and osteosarcoma.
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