Rothmund-Thomson Syndrome Diagnosed during Osteosarcoma Workup in a Child with Biallelic RECQL4 Variants: A Case Report

Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive genodermatosis.RECQL4-associated RTS carries an increased osteosarcoma risk, but diagnosis may be delayed when cutaneous findings are subtle.A 7-year-old girl presented with waddling gait.Imaging revealed left developmental dysplasia of the hip and a 2.3×1.4×4.7-cmlesion involving the epiphysis and metaphysis of the left proximal tibia.Repeat biopsy after a nondiagnostic needle biopsy confirmed fibroblastic osteosarcoma without metastasis.Severe growth failure, metaphyseal dysplasia, sparse hair, and mottled facial pigmentation prompted genetic evaluation.Trio whole-exome sequencing identified maternally inherited RECQL4 c.2161C＞T (p.Arg721Ter), classified as pathogenic, and paternally inherited c.1406_1414del (p.Val469_Gln471del), classified as likely pathogenic, establishing compound heterozygosity.Molecular confirmation of RTS occurred after limb-salvage surgery.She received neoadjuvant and postoperative methotrexate, doxorubicin, and cisplatin.Febrile neutropenia, transfusion-requiring myelosuppression, transaminase elevation, and worsening eczema necessitated dose reductions and treatment delays.Imaging on September 15, 2026, 102 days after chemotherapy completion, showed no evidence of recurrence or metastasis.Childhood osteosarcoma accompanied by growth failure, skeletal abnormalities, and pigmentary findings should prompt evaluation for an inherited cancer-predisposition syndrome.Recognition supports genetic counseling, individualized treatment monitoring, and long-term follow-up.