Abdulkerim KOLKIRAN, Melike ATASEVEN KULALI, Tuğba DAŞAR, Firdevs DİNÇSOY BİR, Ahmet KABLAN, Şükriye YILMAZ, Alişan DAYLAK, Şule YEŞİL, Gürses ŞAHİN
Acta Haematologica Oncologica Turcica - 2026;59(1):38-47
Aim: To characterize the clinical, radiological, and genetic features of genetically confirmed hereditary multiple exostoses (HME) in patients presenting with multiple exostoses and to contribute to the understanding of the phenotypic and genotypic spectrum. Methods: This retrospective cohort study included 21 patients from 13 unrelated families referred to a pediatric genetics clinic for multiple exostoses, with an HME diagnosis confirmed by molecular genetic testing. Clinical findings and available skeletal survey radiographs were reviewed. Identified variants were classified, and segregation analysis was performed when feasible. Results: Ages at presentation ranged from 2.27 to 59.6 years; 14 patients were female, and 7 were male. The most common reasons for referral were a palpable mass and imaging findings. Skeletal survey radiographs were available for 17 patients, all of whom showed multiple exostoses of variable severity. Exostoses most frequently involved the forearm (ulna and radius), femur, lower leg (tibia and fibula), and humerus; involvement of the hands and pelvis was observed at an intermediate frequency. The feet, ribs, scapula, and clavicle were less commonly affected, and no vertebral lesions were identified. As of the most recent follow-up, no malignant transformation has been identified among patients in our cohort (0%). In one of our patients (P21), a stable, non-growing mass was detected in the mesencephalon. Thirteen distinct variants were detected, five of which were novel. Fifteen patients were classified as EXT1-related HME type 1 and six as EXT2-related HME type 2. Variant types comprised seven frameshift variants, four nonsense variants, one missense variant, and one splice-site variant; all were classified as pathogenic/likely pathogenic. Among eight probands with segregation testing available, two variants (25%) were confirmed to be de novo. Conclusion: HME exhibits marked clinical and genetic heterogeneity. Careful assessment of skeletal surveys supports the clinical diagnosis, while molecular confirmation is critical for accurate genetic counseling. The novel variants and the associated phenotypic and radiological findings reported here further expand the disease spectrum.
