Autosomal Dominant Osteopetrosis - Identification of a New Mutation

Osteopetrosis comprises a group of rare skeletal dysplasias characterized by increased bone density and paradoxical bone fragility. Among its forms, autosomal dominant osteopetrosis (ADO) is most frequently associated with mutations in the CLCN7 gene, encoding a chloride antiporter essential for osteoclast function. CLCN7-related ADO results from impaired osteoclast acidification and decreased bone resorption. Although bone mineral accumulation is characteristic, skeletal fragility and complications such as osteomyelitis and cranial nerve compression may occur.

We report three related individuals who exhibited increased bone density and pathognomonic radiographic appearances of "bone-within-bone" and "sandwich-vertebrae". Genetic testing identified a novel heterozygous CLCN7 mutation, confirming the diagnosis of ADO. This family's novel mutation expands the known genotypic spectrum of ADO and underscores the value of genetic testing in adult-onset bone dysplasias with atypical presentation.

This case report highlights the diagnostic importance of recognizing characteristic radiographic patterns and confirming them through molecular analysis, emphasizing the need for multidisciplinary follow-up and appropriate genetic counselling.

Characteristic radiographic features such as "bone-within-bone" and "sandwich vertebrae" are highly suggestive of autosomal dominant osteopetrosis.CLCN7 pathogenic variants account for most cases of autosomal dominant osteopetrosis and justify early genetic testing.This case highlights a novel CLCN7 mutation, reinforcing the genetic heterogeneity of osteopetrosis and the value of family screening.