Turkish Archives of Pediatrics
Original Article

Phenotypic and Molecular Spectrum of a Turkish Cohort with Hereditary Multiple Osteochondromas

1.

Department of Pediatric Genetics, İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, İstanbul, Turkey

2.

Department of Pediatric Genetics, İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, İstanbul, Turkey

3.

Department of Medical Genetics, Akdeniz University Faculty of Medicine, Antalya, Turkey

4.

Department of Pediatric Genetics, Akdeniz University Faculty of Medicine, Antalya, Turkey

5.

Department of Orthopedics and Traumatology, İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Istanbul, Turkey

6.

Department of Orthopedics and Traumatology, Metin Sabancı Baltalimanı Bone Diseases Training and Research Center, Health Sciences University, İstanbul, Turkey

7.

Department of Radiology, İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, İstanbul, Turkey

Turk Arch Pediatr 2023; 58: 376-381
DOI: 10.5152/TurkArchPediatr.2023.23011
Read: 618 Downloads: 292 Published: 01 July 2023

Objective: Hereditary multiple osteochondromas is an autosomal dominant disorder caused by heterozygous pathogenic variants in EXT1 or EXT2. We aimed to evaluate the clinical and molecular findings of a Turkish cohort with hereditary multiple osteochondroma.

Materials and Methods: Thirty-two patients aged 1.3-49.6 years from 22 families were enrolled. Genetic analyses were made by EXT1 and/or EXT2 sequencing and chromosomal microarray analyses.

Results: We found 17 intragenic pathogenic variants in EXT1 (13/17) and EXT2 (4/17), 12 of which are novel. Four probands had EXT1 deletions, including 2 patients with partial EXT1 microdeletions involving exons 2-11 and 5-11, and 2 patients with whole-gene deletions. In 21 variants, the frequency of truncating and missense variants was 76.1% and 23.8%, respectively. Two families had no detectable variants in EXT1 and EXT2. All patients had multiple osteochondromas at the long bones, mainly at the tibia, forearm, femur, and humerus. Bowing deformity of the forearms (9/32) and the lower extremities (2/32), and scoliosis (6/32) were observed. The clinical severity was not different between patients with EXT1 or EXT2 variants. One patient with an EXT2 variant and another with an EXT1 microdeletion had the most severe phenotype with class III disease. Four patients with no EXT1 or EXT2 variants had milder phenotypes. Intrafamilial variability in disease severity was not observed.

Conclusion: We report a hereditary multiple osteochondroma cohort with clinical and molecular data including 12 novel intragenic variants in EXT1 or EXT2, and 4 microdeletions involving EXT1. Taken together, our data expand the existing knowledge of the phenotype–genotype spectrum in hereditary multiple osteochondroma.

Cite this article as: Güneş N, Uludağ Alkaya D, Toylu A, et al. Phenotypic and molecular spectrum of a Turkish cohort with hereditary multiple osteochondromas. Turk Arch Pediatr. 2023;58(4):376-381.

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EISSN 2757-6256