Gnathodiaphyseal dysplasia: Severe atypical presentation with novel heterozygous mutation of the anoctamin gene (ANO5)

Abstract

Gnathodiaphyseal dysplasia (GDD; OMIM #166260) is an ultra-rare autosomal dominant disorder caused by heterozygous mutation in the anoctamin 5 (ANO5) gene and features fibro-osseous lesions of the jawbones, bone fragility with recurrent fractures, and bowing/sclerosis of tubular bones. The physiologic role of ANO5 is unknown. We report a 5-year-old boy with a seemingly atypical and especially severe presentation of GDD and unique ANO5 mutation. Severe osteopenia was associated with prenatal femoral fractures, recurrent postnatal fractures, and progressive bilateral enlargement of his maxilla and mandible beginning at ~2months-of-age that interfered with feeding and speech and required four debulking operations. Histopathological analysis revealed benign fibro-osseous lesions resembling cemento-ossifying fibromas of the jaw without psammomatoid bodies. A novel, de novo, heterozygous, missense mutation was identified in exon 15 of ANO5 (c.1553G>A; p.Gly518Glu). Our findings broaden the phenotypic and molecular spectra of GDD. Fractures early in life with progressive facial swelling are key features. We assessed his response to a total of 7 pamidronate infusions commencing at age 15months. Additional reports must further elucidate the phenotype, explore any genotype-phenotype correlation, and evaluate treatments.

Recurrent femoral shaft fractures in a child with gnathodiaphyseal dysplasia: a case report

“…On the other hand, little is known about medications for patients with GDD. Ghada et al reported a case of GDD treated with a bisphosphonate [1]. They demonstrated that bisphosphonate therapy did improve BMD of the spine.…”

“…Gnathodiaphyseal dysplasia (GDD) is one of the extremely rare autosomal dominant diseases characterized by cemento-osseous lesions of the jawbones, bone fragility, and diaphyseal sclerosis of tubular bones [1]. The patients with GDD are prone to sustain fractures by minor accidents.…”

“…To date, reports of approximately 80 affected individuals are available, and most of them have suffered fractures [1, 2]. Although the underlying mechanism of bone fragility has not been completely elucidated, recent investigations demonstrated that mutations in the ANO5 gene were associated with the pathogenesis of GDD [1]. There are several reports that discuss the treatment of facial bone lesions [3, 4].…”

Regarding the Use of the Term “Cementum” in Fibro-Osseous Lesions of the Craniofacial Skeleton

“…Lastly, there is a group of very rare form of jaw fibroosseous lesions which is associated with genetic abnormality. It includes familial gigantiform cementoma (FGC) and gnathodiaphyseal dysplasia (GDD) [5,6]. These are characterized by early onset multifocal, multiquadrant rapidly progressive expansive lesions that may be massive.…”

“…A mutated (GDD1) gene has been identified in multiple GDD families. The gene is also known as anoctamin 5 (ANO5) [6].…”