[Clinical and genetic characteristics of osteopetrosis in children].

OBJECTIVES

To study the clinical and genetic characteristics of osteopetrosis (OPT) in children.

METHODS

A retrospective analysis was performed on the clinical data of 14 children with OPT. Whole-exome sequencing was used to detect pathogenic genes, and clinical phenotypes and genotypic features were summarized.

RESULTS

Among the 14 children (10 males and 4 females), the median age at diagnosis was 8 months. Clinical manifestations included systemic osteosclerosis (14 cases, 100%), anemia (12 cases, 86%), infections (10 cases, 71%), thrombocytopenia (9 cases, 64%), hepatosplenomegaly (8 cases, 57%), and developmental delay (5 cases, 36%). Malignant osteopetrosis (MOP) cases had lower platelet counts, creatine kinase isoenzyme, and serum calcium levels, but higher white blood cell counts, lactate dehydrogenase, and alkaline phosphatase levels compared to non-MOP cases (<0.05). Genetic testing identified 15 variants in 12 patients, including 8 variants in the gene (53%), 6 in the gene (40%), and 1 in the gene (7%). Three novel variants were identified: c.2351G>C, c.1215-43C>T, and c.1534G>A. All four patients with variants exhibited MOP clinical phenotypes. Of the seven patients with variants, 4 presented with intermediate OPT, 2 with benign OPT, and 1 with MOP.

CONCLUSIONS

Clinical phenotypes of OPT in children are heterogeneous, predominantly involving and gene variants, with a correlation between clinical phenotypes and genotypes.