Radiographic abnormalities in Rothmund-Thomson syndrome and genotype-phenotype correlation with RECQL4 mutation status.
OBJECTIVE
The purpose of this study was to summarize the radiographic skeletal findings in patients with Rothmund-Thomson syndrome (RTS) and to determine whether there is an association between the presence of skeletal abnormalities and the mutational status of the RECQL4 gene.


METHODS
Twenty-eight subjects with RTS underwent skeletal surveys and RECQL4 DNA mutation testing. Radiographs were reviewed by two radiologists. RECQL4 mutation testing by DNA sequencing of the gene was performed by a diagnostic laboratory. Genotype-phenotype analysis by Fisher's exact test was performed to investigate whether there was a correlation between mutation status and skeletal abnormalities.


RESULTS
Twenty-one (75%) of the subjects had at least one significant skeletal abnormality, the more common being abnormal metaphyseal trabeculation, brachymesophalangy, thumb aplasia or hypoplasia, osteopenia, dislocation of the radial head, radial aplasia or hypoplasia, and patellar ossification defects. Three subjects had a history of destructive bone lesion (osteosarcoma). Genotype-phenotype analysis showed a significant correlation between RECQL4 mutational status and the presence of skeletal abnormalities (p < 0.0001).


CONCLUSIONS
Skeletal abnormalities are frequent in persons with RTS. Many of these abnormalities are not clinically apparent but are detectable on radiographs. The presence of skeletal abnormalities correlates with RECQL4 mutation status, which has been found to correlate with risk of osteosarcoma. Skeletal surveys aid in both diagnosis and management of RTS.
Mehollin-Ray
Amy R
AR
Department of Radiology, Baylor College of Medicine, Houston, TX 77030, USA.
Kozinetz
Claudia A
CA
Schlesinger
Alan E
AE
Guillerman
R Paul
RP
Wang
Lisa L
LL
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D017880:Limb Deformities, Congenital / Q000000981:diagnostic imaging* / Q000235:genetics; D008297:Male; D009154:Mutation; D010641:Phenotype; D011859:Radiography; D053484:RecQ Helicases / Q000235:genetics; D011038:Rothmund-Thomson Syndrome / Q000000981:diagnostic imaging* / Q000235:genetics
C506731:RECQL4 protein, human; D053484:RecQ Helicases