Gnathodiaphyseal Dysplasia: report of a rare case with a de novo insertion mutation of ANO5 gene and review of the literature.

Introduction

Gnathodiaphyseal dysplasia (GDD) is a rare autosomal dominant disorder caused by point mutations in anoctamin 5 (ANO5) gene (11p14.3), characterized by sclerosis of the tubular bones and benign fibro-osseous (BFO) lesions of the jaws. GDD may also occur sporadically due to missense mutations, while de novo ANO5 insertion mutations have only been rarely described.

Case description

A 10-year-old boy presented for evaluation of asymptomatic radiopaque lesions involving the posterior mandible, bilaterally. Multiple bone biopsies were performed with features of BFO. Sequential imaging with panoramic radiographs and cone beam computer tomography scans for the next 3 years revealed that the lesions gradually increased in size, whereas multiple new distinct hyperdense areas with relatively well-defined borders throughout both jaws were observed. Eventually, painful symptoms developed in the area of the left TMJ, associated with the development of lesions in the left mandibular condyle. Genetic evaluation of the patient's family history of four generations did not render evidence of a hereditary condition, while craniognathic radiographic examination of both parents was normal. Further molecular investigation with Whole Exome Sequencing in DNA isolated from a whole blood sample detected a heterozygous insertion mutation in the ANO5 gene. Taken together, a final diagnosis of GDD with a de novo ANO5 mutation was rendered.

Conclusions

GDD is characterized by genetic disruption of ANO5, a calcium-activated chloride channel, usually caused by inherited single amino-acid substitutions, resulting in impaired osteoclastogenesis. GDD with a de novo insertion mutation in ANO5, as in our case, has been described only once before. The exact pathogenesis of GDD remains unclear, necessitating further studies to elucidate the whole genetic and phenotypic spectrum of the disorder. A multidisciplinary approach to diagnosis with involvement of oral and maxillofacial pathologists, radiologists and geneticists is mandatory.